OBJECTIVE: To create a protocol that could be used to construct chemical information database from scientific literature quickly and automatically. METHODS: Scientific literature, patents and technical reports from different chemical disciplines were collected and stored in PDF format as fundamental datasets. Chemical structures were transformed from published documents and images to machine-readable data by using the name conversion technology and optical structure recognition tool CLiDE. In the process of molecular structure information extraction, Markush structures were enumerated into well-defined monomer molecules by means of QueryTools in molecule editor ChemDraw. Document management software EndNote X8 was applied to acquire bibliographical references involving title, author, journal and year of publication. Text mining toolkit ChemDataExtractor was adopted to retrieve information that could be used to populate structured chemical database from figures, tables, and textual paragraphs. After this step, detailed manual revision and annotation were conducted in order to ensure the accuracy and completeness of the data. In addition to the literature data, computing simulation platform Pipeline Pilot 7.5 was utilized to calculate the physical and chemical properties and predict molecular attributes. Furthermore, open database ChEMBL was linked to fetch known bioactivities, such as indications and targets. After information extraction and data expansion, five separate metadata files were generated, including molecular structure data file, molecular information, bibliographical references, predictable attributes and known bioactivities. Canonical simplified molecular input line entry specification as primary key, metadata files were associated through common key nodes including molecular number and PDF number to construct an integrated chemical information database. RESULTS: A reasonable construction protocol of chemical information database was created successfully. A total of 174 research articles and 25 reviews published in Marine Drugs from January 2015 to June 2016 collected as essential data source, and an elementary marine natural product database named PKU-MNPD was built in accordance with this protocol, which contained 3 262 molecules and 19 821 records. CONCLUSION This data aggregation protocol is of great help for the chemical information database construction in accuracy, comprehensiveness and efficiency based on original documents. The structured chemical information database can facilitate the access to medical intelligence and accelerate the transformation of scientific research achievements.
Data Mining ; Databases, Chemical ; Molecular Structure ; Software

To study the effect of different storage time on the chemical compositions and sulfur dioxide residues of sulfur-fumigated Gastrodiae Rhizoma (GR), and provide scientific basis for solving the quality and safety issues of sulfur-fumigated traditional Chinese medicinal materials. GR, sulfur-fumigated GR and its medicinal slices were stored under the same conditions, and then 8 active ingredients and sulfur dioxide residues were measured respectively. The results showed that the content of gastrodins in sulfur-fumigated GR and its medicinal slices was significantly lower than that in the non-fumigated GR. Moreover, the content of sulfur dioxide residue in sulfur-fumigated GR was significantly higher than that in its medicinal slices. That is to say, sulfur fumigation degree had significantly higher effect on GR quality as compared with its medicinal slices. During the whole storage time (8 months), the content of the eight chemical components in GR was not changed greatly in general. However, after the storage for 4 months, the content of 8 components and sulfur dioxide residues in all of GR samples were significantly changed. In particular, the content of sulfur dioxide residue in GR medicinal materials decreased up to 50% or more.
Drug Storage ; Drugs, Chinese Herbal ; chemistry ; Fumigation ; Gastrodia ; chemistry ; Rhizome ; chemistry ; Sulfur ; Sulfur Dioxide ; analysis

As Gastrodiae Rhizoma (GR) is one of the herbs more seriously affected by sulfur fumigation, so its quality has been always of a great concern. In this paper, GR samples collected from eight main producing areas and in three forms were fumigated with sulfur and quantitatively and qualitatively analyzed based on UPLC-Q-TOF-MS/MS. The results showed that the contents of gastrodin, parishin, parishin B and parishin C were decreased, while the content of parishin E was increased after sulfur fumigation treatment. Besides, a new sulfur marker named p-hydroxybenzyl hydrogen sulfite was produced in sulfur-fumigated GR samples. As compared with producing origins, forms had a greater impact on the quality of GR, especially in Hongtianma and Wutianma. Besides, the contents of gastrodins and parishins in Hongtianma from Jilin were lowest as compared with those in other producing areas. This might be correlated with planting patterns and environmental factors. In conclusion, sulfur fumigation has a more obvious impact on the quality of GR than origins and forms, which is attributed to the generation of new sulfur fumigated markers.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; standards ; Fumigation ; Gastrodia ; chemistry ; Quality Control ; Rhizome ; chemistry ; Sulfur ; Tandem Mass Spectrometry

Studies on the characteristic chemical markers of sulfur fumigation have become an effective auxiliary way for quality control of traditional Chinese medicine. This study established a quantitative analysis method for the determination of -hydroxybenzyl hydrogen sulfite (-HS) in Gastrodiae Rhizoma (GR) based on UPLC-MS/MS. Then, 37 batches of GR were screened, and the results showed that 27 batches of them were sulfur-fumigated. Especially, the GR samples in Yunnan producing areas were sulfur-fumigated more seriously. Based on the stability of -HS after different storage time and heat treatment methods, it was found that the content of -HS was stable and reliable in the storage period of 8 months and under normal heat treatment (50, 60, 70, 80 °C) conditions. In conclusion, this study shows a high sensitivity, good selectivity and good stability of -HS, which can provide reference for the quality control and sulfur fumigation screening of GR.
China ; Chromatography, Liquid ; Drugs, Chinese Herbal ; chemistry ; standards ; Fumigation ; Gastrodia ; chemistry ; Quality Control ; Rhizome ; chemistry ; Sulfites ; analysis ; Sulfur ; Tandem Mass Spectrometry

The traditional sulfur fumigation processing method has been widely used in the initial processing and storage of traditional Chinese medicinal materials due to its economy, efficiency, convenience, high operability and effect on mold and insect prevention. However, excessive sulfur fumigation of traditional Chinese medicinal materials would lead to the changes in chemical compositions, and even endanger human health. This study showed that traditional Chinese medicinal materials were sulfur fumigated directly after being harvested for quick drying, or fumigated after being weted in the storage process for preventing mold and insects. We found that the sulfur dioxide limits for traditional Chinese medicinal materials were stricter than those for foods. Based on the existing limit standards, we obtained the data of sulfur dioxide residues for 35 types of traditional Chinese medicinal materials in a total of 862 batches. According to the limit standard in the Chinese Pharmacopoeia (150， 400 mg·kg⁻¹), the average over-standard rate of sulfur dioxide was as high as 52.43%, but it was reduced to 29.47% if calculated based on the limit for vegetable additive standard (500 mg·kg⁻¹). Sulfur fumigation issue shall be considered correctly: sulfur dioxide is a type of low toxic substance and less dangerous than aflatoxin and other highly toxic substances, and a small amount of residue would not increase the toxicity of traditional Chinese medicinal materials. However, sulfur fumigation might change the content of chemical substances and affect the quality of traditional Chinese medicinal materials. Furthermore, the exposure hazards of toxic substances are comprehensively correlated with exposure cycle, exposure frequency, and application method. In conclusion, it is suggested to strengthen the studies on the limit standard of traditional Chinese medicinal materials, formulate practical and feasible limit standard for sulfur dioxide residues in traditional Chinese medicinal materials that are consistent with the medication characteristics of traditional Chinese medicinal materials and can guarantee people's demand for safe medication.
Drugs, Chinese Herbal ; standards ; Fumigation ; Medicine, Chinese Traditional ; Sulfur ; Sulfur Dioxide ; standards

Recently, integrative pharmacology(IP) has become a pivotal paradigm for the modernization of traditional Chinese medicines(TCM) and combinatorial drugs discovery, which is an interdisciplinary science for establishing the in vitro and in vivo correlation between absorption, distribution, metabolism, and excretion/pharmacokinetic(ADME/PK) profiles of TCM and the molecular networks of disease by the integration of the knowledge of multi-disciplinary and multi-stages. In the present study, an internet-based Computation Platform for IP of TCM(TCM-IP, www.tcmip.cn) is established to promote the development of the emerging discipline. Among them, a big data of TCM is an important resource for TCM-IP including Chinese Medicine Formula Database, Chinese Medical Herbs Database, Chemical Database of Chinese Medicine, Target Database for Disease and Symptoms, et al. Meanwhile, some data mining and bioinformatics approaches are critical technology for TCM-IP including the identification of the TCM constituents, ADME prediction, target prediction for the TCM constituents, network construction and analysis, et al. Furthermore, network beautification and individuation design are employed to meet the consumer's requirement. We firmly believe that TCM-IP is a very useful tool for the identification of active constituents of TCM and their involving potential molecular mechanism for therapeutics, which would wildly applied in quality evaluation, clinical repositioning, scientific discovery based on original thinking, prescription compatibility and new drug of TCM, et al.

Objective To observe the clinical, neuropathogical, neurophysiological characteristics of Charcot-Marie-Tooth disease, type 1A (CMT1A) which was similar to chronic inflammatory demyelinating polyradiculoneuropathy(CIDP).Methods The clinical data, neuroelectrophysiological changes and pathological features of sural nerve biopsy were taken from 2 CMT1A patients who were proven to be 17p12 duplication with CIDP features, and analyzed comprehensively. Results Two CMT1A cases with classical chronic course showed both subacute course and clinical manifestations similar to CIDP, however, the changes of neuroelectrophysiology and pathological characteristics of the nerve biopsy in 2 cases were different from CIDP in some way. We confirmed the chronic inflammatory demyelinating type of the CMT1A patients whom the immunotherapy was effective on.Conclusion The classical CMT1A 17p12 duplication patients who obtained immunotherapy effects might resemble CIDP both in clinical course and manifestation.

Objective To demonstrate the carbonic anhydrase Ⅲ (CAⅢ) for 25 000 protein decreased in skeletal muscle of myasthenia gravis (MG). Methods The protein molecular properties responsible to antibodies against 25 000 protein and CAⅢ were analyzed by a combination method of two-dimensional electrophoresis and immuno-Western blot. Competitive binding reactions of the antibodies to the purified 25 000 protein and muscular homogenate were observed by using immuno-Dot blot and immuno-Western blot, respectively. The expression of CAⅢ from normal and MG muscles was detected by immuno-Western blot. Results Combination analysis of two-dimensional electrophoresis and immuno-Western blot showed that the protein of immunological responsible to antibodies against 25 000 protein and CAⅢ had an identical molecular mass and isoelectric point. Competitive binding reactions proved that 25 000 protein and CAⅢ were the same substance, either by immuno-Dot blot or by immuno-Western blot. In addition, a much similar result was obtained when the levels of 25 000 protein from normal and MG muscles were detected by antibodies against 25 000 protein and (CAⅢ) by immuno-Western blot. Conclusion 25 000 protein decreased in the MG skeletal muscle was proved to be just a known protein CAⅢ, which made a basis for further exploring the relationship of CAⅢ deficiency and MG pathogenesis.

Objective To explore sub-clinical items in evaluating the prognosis of epileptic patients,the study on differences of regional cerebral blood flow (rCBF) in both effective treated and incomplete-controlled patients with idiopathic generalized tonic clonic seizure (GTCS) was carried out.Methods Interictal rCBF measurements using 99m Tc-ethyl cysteinates dimmer (ECD) SPECT was performed on 29 effective treated idiopathic GTCS patients and 12 incomplete controlled idiopathic GTCS patients. The rCBF distribution was semi-quantitatively analyzed by regions of interest (ROIs) comparing with abnormal rate of interictal hypoperfusion rCBF,clinical seizure time and EEG.Results ROI analysis showed that rCBF decreased in basal ganglia and thalamus of incomplete controlled patients with idiopathic GTCS compared to that of effective treated ones′ significantly ( P

Objective To evaluate the possible molecular pathogenesis of intractable temporal lobe epilepsy. The potassium ion channel gene KCNJ4 encodes one of the subfamilies of Kir channels, Kir2.3 subunit, which may play an important role in modulating neuronal excitation. Interference in the function or expression of this gene would cause disturbance of ionic concentrations, thus leading to seizure activity. Methods Reverse transcription polymerase chain reaction (RT-PCR) and Western-blot analysis were used to measure the expression alterations of KCNJ4 mRNA as well as its protein product Kir2.3 channel in temporal cortex samples from patients who had undergone temporal lobectomy for intractable epilepsy (n=12). Tissue from 10 subjects who did not have epilepsy served as controls. Results The expression of KCNJ4 mRNA (0.438?0.178) and its protein Kir2.3 (M 50=0.063) were significantly decreased in epileptic brain compared with the controls (P