Chinese patent medicine with double identity was a special phenomenon, and many preparations not only were prescription drugs but also over the counter ( OTC) drugs, which brought a lot of trouble. Based on statistics of list of OTC medicines of CFDA, related varieties, route of administration and functions of these drugs were searched. The causes of insufficient were analyzed and the potential risk was investigated. To ensure the safety of drug usage for the patient, risk management system should be set up by improving the technical requirements for registration, improving the drug labels and manuals, playing the role of pharmacists in pharmacy services and raising awareness of doctor and patient for these drugs.
China ; Humans ; Nonprescription Drugs ; adverse effects ; Risk Management

This study investigated the effects of different frequencies of repetitive transcranial magnetic stimulation (rTMS) on chronic neuropathic pain in rats.The behavior of rats with experimental chronic neuropathic pain was observed,and the expression of neuronal nitric oxide synthase (nNOS) in the ipsilateral dorsal root ganglions (DRGs) and the activation and proliferation of astrocytes in the ipsilateral spinal dorsal horn were detected.Thirty-two male Sprague-Dawley rats were randomly divided into four groups:sham-operated group,sham-rTMS group,1 Hz group and 20 Hz group (8 rats in each group).Chronic constriction nerve injury induced by sciatic nerve ligation was made to establish the models of the chronic neuropathic pain in rats except those in the sham-operated group.Then we applied different frequencies of rTMS to the primary motor cortex (M1) contralateral to the pain side once daily for 10 consecutive days.Pain behavior scores were observed before and after treatment.Western blot analysis was used to detect the expression of nNOS in ipsilateral L4-6 DRGs.Double immunofluorescent labeling for glial fibrillary acidic protein (GFAP) and 5-bromo-2-deoxyuridine (BrdU) was employed to observe the activation and proliferation of astrocytes in the ipsilateral L4-6 spinal dorsal horn.After rTMS treatment,the spontaneous pain behavior scores were significantly lower in the 20 Hz group than those in the sham-rTMS group (P＜0.05).Moreover,the brush-evoked pain behavior scores were significantly lower in the 20 Hz group than those in the sham-rTMS and 1 Hz group (P＜0.05),suggesting that the spontaneous pain and brush-evoked pain in the 20 Hz group were significantly alleviated.Western blot analysis revealed that the expression of nNOS in ipsilateral L4-6 DRGs was significantly decreased in the 20 Hz group as compared with the sham-rTMS group and the 1 Hz group (P＜0.01) after rTMS treatment.Double immunofluorescence suggested that the expression of GFAP and the co-localization with BrdU in astrocytes were less in the sham-operated group than those in the sham-rTMS group and the 1 Hz group in L4-6 spinal dorsal horn ipsilateral to the neuropathic pain.After rTMS treatment,the expression of GFAP and the co-localization with BrdU decreased in the 20 Hz group as compared with the sham-rTMS group and the 1 Hz group (P＜0.05).In addition,the alleviation degree of spontaneous pain and brush-evoked pain in the 20 Hz group was negatively correlated with the expression of nNOS in ipsilateral DRGs and the number of GFAP/BrdU co-labelled astrocytes in L4-6 spinal dorsal horn ipsilateral to the neuropathic pain (P＜0.05).It was suggested that high-frequency rTMS may relieve neuropathic pain through down-regulating the overexpression of nNOS in ipsilateral DRGs and inhibiting the activity and proliferation of astrocytes in L4-6 spinal dorsal horn ipsilateral to the neuropathic pain.

During the routine impurity profile of lisinopril bulk drug by HPLC (high-performance liquid chromatography), a potential impurity was detected. Using multidimensional NMR (nuclear magnetic resonance) technique, the trace-level impurity was unambiguously identified to be 2-(-2-oxo-azocan-3-ylamino)-4-phenyl-butyric acid after isolation from lisinopril bulk drug by semi-preparative HPLC. Formation of the impurity was also discussed. To our knowledge, this is a novel impurity and not reported elsewhere.
Butyrates ; analysis ; isolation & purification ; Drug Contamination ; Lisinopril ; analysis ; Magnetic Resonance Spectroscopy ; Models, Molecular

BACKGROUNDRegulatory T-cells (Treg) play key roles in suppressing cell-mediated immunity in cancer patients. Little is known about perioperative Treg fluctuations in nonsmall cell lung cancer (NSCLC). Video-assisted thoracoscopic (VATS) lobectomy, as a minimal invasive procedure for treating NSCLC, may have relatively less impact on the patient's immune system. This study aimed to observe perioperative dynamics of circulating Treg and natural killer (NK) cell levels in NSCLC patients who underwent major lobectomy by VATS or thoracotomy.

METHODSTotally, 98 consecutive patients with stage I NSCLC were recruited and assigned into VATS or thoracotomy groups. Peripheral blood samples were taken on 1-day prior to operation, postoperative days (PODs) 1, 3, 7, 30, and 90. Circulating Treg and NK cell counts were assayed by flow cytometry, defined as CD4 + CD25 + CD127 low cells in CD4 + lymphocytes and CD56 + 16 + CD3- cells within CD45 + leukocytes respectively. With SPSS software version 21.0 (SPSS Inc., USA), differences between VATS and thoracotomy groups were determined by one-way analysis of variance (ANOVA), and differences between preoperative baseline and PODs in each group were evaluated by one-way ANOVA Dunnett t-test.

RESULTSIn both groups, postoperative Treg percentages were lower than preoperative status. No statistical difference was found between VATS and thoracotomy groups on PODs 1, 3, 7, and 30. On POD 90, Treg percentage in VATS group was significantly lower than in thoracotomy group (5.26 ± 2.75 vs. 6.99 ± 3.60, P = 0.012). However, a higher level of NK was found on all PODs except on POD 90 in VATS group, comparing to thoracotomy group.

CONCLUSIONSLower Treg level on POD 90 and higher NK levels on PODs 1, 3, 7, 30 in VATS group might imply better preserved cell-mediated immune function in NSCLC patients, than those in thoracotomy group.

Aged ; Carcinoma, Non-Small-Cell Lung ; immunology ; surgery ; Female ; Flow Cytometry ; Humans ; Killer Cells, Natural ; immunology ; Male ; Middle Aged ; Postoperative Period ; T-Lymphocytes, Regulatory ; immunology ; Thoracic Surgery, Video-Assisted ; methods ; Thoracotomy ; methods

OBJECTIVETo characterize the structural and the functional feature of a novel gene HSPCSET isolated from human CD34+ hematopoietic stem/progenitor cells (HS/PCs).

METHODSBioinformatic technology was used to identify the structural features of the HSPCSET protein and perform the multiple sequence alignment. Yeast-two-hybrid system was used to identify the proteins interacting with the HSPCSET protein. After sequencing, we selected out the positive clones which had clear functions, and carried out beta-gal experiment and GST pull down assay to confirm the results. The cellular location of the HSPCSET was checked by immunofluorescence assay.

RESULTSThe HSPCSET protein belongs to a SET domain family, which is evolutionarily conserved across species. It implied that HSPCSET may have biologically important function. Using yeast-two-hybrid system, we showed that the protein sequence with SET domain might bind to 13 proteins, which involved in signaling transduction, transcriptional regulation, apoptosis, tumorigenesis, development, etc. And 4 proteins (GADD34, SIVA, DNAJ and PHF1) were confirmed by one-on-one back of the hybrid experiment, beta-gal test and GST pull down assay. When GADD34 and HSPCSET were co-transfected, they co-localized in the nucleus, suggesting a strong interaction.

CONCLUSIONThe novel gene HSPCSET is likely to have biologically important function. This study provides the basis for further studies of its function in hematopoiesis and tumorigenesis.

Amino Acid Sequence ; Animals ; Antigens, Differentiation ; metabolism ; Cell Cycle Proteins ; metabolism ; Computational Biology ; Conserved Sequence ; Hematopoietic Stem Cells ; metabolism ; Humans ; Molecular Sequence Data ; Protein Phosphatase 1 ; Protein Structure, Tertiary ; Proteins ; chemistry ; genetics ; metabolism ; Sequence Homology, Amino Acid ; Two-Hybrid System Techniques

UNLABELLEDTo reduce the huge labor-cost in the screening in traditional monoclonal antibody generation, We established a new system for monoclonal antibody generation integrating with protein array. BALB/c mice were immunized by eight recombinant proteins respectively, and the positive hybridoma cells were obtained by cell fusion and ELISA screening. All the eight kinds of positive hybridoma cells were mixed, cloned, screened by protein array, and definite dilution cloned.

RESULTS175 single cell clones were obtained by complex cloning, and 119 of those were positive clones. Then 8 positive cell lines were generated by the following 2 rounds definite dilution cloning. By comparing with the traditional method, we got 8 monoclonal antibodies using the combined protein array screening and multiplex cloning method in 1 cycle, and fewer amounts of antigens were used. As a result, the combined protein array and multiplex cloning method could be used as an economical, rapid and simple tool applying in high throughput monoclonal antibody generation.

Animals ; Antibodies, Monoclonal ; biosynthesis ; immunology ; isolation & purification ; Female ; Humans ; Hybridomas ; metabolism ; Mice ; Mice, Inbred BALB C ; Protein Array Analysis

Epsilon 3xenergy dispersive X-ray fluorescence spectrometer (EDXRF) was used to analyze the major and minor elements in marine sediments collected from the Indian Ocean on-site. Results obtained by EDXRF were compared with those by inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-optical emission spectrometry (ICP-OES) in the laboratory A total of 24 elements in marine sediment samples,namely Al2O3,MgO,Fe2O3,Na2O,K2O,CaO,Mn,P,Ti,Ba,Sr,V,Zn, Zr, Co,Ni,Cu,Ga,Rb,Y,Nb,Mo,Nd,Pb and Th were measured,and a good agreement was found for these elements(R2>0.9),except for Al2O3,and Ga,Nb and Th with content lower than 30 μg/g. The mean relative deviations of EDXRF method were less than 10% for all of the above mentioned major elements, except for MgO in low concentration and P in high concentration. The mean relative deviations were less than 25% for all of the above mentioned trace elements,except for Sr(>700 μg/g),Mo(<20 μg/g) and Nb. In general, precision and accuracy of EDXRF method were good enough for detection of marine sediments. Taking into account all these facts, the EDXRF method proposed here was proved to be an effective tool for element determination in marine sediment on-site,and it would provide a new technical support to investigate the spatial distribution of mineral resources in marine geological survey.

OBJECTIVETo better understand the mechanisms of the fetal hematopoiesis turn over from primitive to definitive hematopoiesis through the expression level of c-kit(+) and sca-1(+), and major characters of gene expression profile of these cells.

METHODSc-kit and sca-1 expression level were monitored with fluorescence activated cell sorting (FACS) of the mononuclear cells from mouse yolk sac and fetal liver, while gene expression profile was carried out with EST sequencing strategy.

RESULTSThe Sca-1(+) cells were increased while the c-kit(+) cells decreased with the embryonic development. Through profiling the functionally identified known genes, most of the highly expressed were globin genes, especially of embryonic types.

CONCLUSIONThe erythropoiesis played a key role in early fetal hematopoiesis in mammalian.

Animals ; Antigens, Ly ; genetics ; metabolism ; Cell Differentiation ; genetics ; Flow Cytometry ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Liver ; cytology ; embryology ; metabolism ; Membrane Proteins ; genetics ; metabolism ; Mice ; Mice, Inbred C57BL ; Proto-Oncogene Proteins c-kit ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; Yolk Sac ; cytology ; embryology ; metabolism

OBJECTIVETo study whether all-trans retinoic acid (ATRA) combined with arsenic trioxide (As(2)O(3)) in acute promyelocytic leukemia (APL) treatment could further improve the clinical and molecular remission rate.

METHODThirty one newly-diagnosed APL patients of whom 15 were males, 16 females and median age 35.4 years entered into the study. They were treated with ATRA 25 mg x m(-2) x d(-1) combined with As(2)O(3) 0.16 mg x kg(-1) x d(-1) until complete remission (CR). The doses were adjusted according to white blood cell (WBC) counts, occurrence of RA syndrome and the status of liver function. CR rate, time of reaching clinical and molecular remission and side effects were observed.

RESULTTwo patients died 2 approximately 3 days after the treatment due to intracranial hemorrhage, and 29 (93.5%) achieved CR. The average time for achieving CR was 25.1 +/- 3.9 days. Hyperleukocytosis emerged in 66.5% and hepatic damages in 65.5% of the patients, they were ameliorated within one week after reduction of the As(2)O(3) dose or its suspension. The PML/RAR alpha fusion gene that was positive in all 29 patients before treatment turned negative only in 3 cases (10.3%) after obtaining CR (CR1) and in 10/13 cases (77%) after consolidation treatment. Up to now (1-8 months follow-up), all 29 patients remain in CR1.

CONCLUSIONATRA combined with As(2)O(3) in de novo APL treatment can yield a high CR rate without intolerable side effects. Long term effect needs further observation.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Arsenicals ; administration & dosage ; adverse effects ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gene Expression ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; genetics ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; genetics ; Oxides ; administration & dosage ; adverse effects ; Remission Induction ; Time Factors ; Treatment Outcome ; Tretinoin ; administration & dosage ; adverse effects

OBJECTIVETo investigate the potential effects of arsenic trioxide (As(2)O(3)) combined with 8-(4-chlorophenylthio) adenosine 3', 5'-cyclic monophosphate (8-CPT-cAMP) on the retinoic acid (RA)-resistant acute promyelocytic leukemia (APL) cells.

METHODSThe RA resistant APL cell lines NB4-R1 and NB4-R2 were used as in vitro models. The effect of As(2)O(3) and/or 8-CPT-cAMP was evaluated according to cellular morphology, cell surface antigen and nitroblue-tetrazolium (NBT) assay. Meanwhile, immunofluorescence analysis and Western blot assay were used to detect the degradation of PML-RAR alpha fusion protein and the change of several key cell cycle regulatory proteins in these cells before and after the treatment.

RESULTSLow dose of As(2)O(3) (0.25 micromol/L) synergized with 8-CPT-cAMP (200 micromol/L) in inducing differentiation of NB4-R1 and NB4-R2 cells, while neither of these two drugs alone could induce differentiation of these cells. In addition, 8-CPT-cAMP was able to inhibit the cell growth by modulating the expression of some important cell cycle regulators and to facilitate the As(2)O(3)-mediated degradation of PML-RAR alpha fusion protein.

CONCLUSIONSAs(2)O(3) combined with 8-CPT-cAMP could induce differentiation of RA-resistant APL cells.

Antineoplastic Agents ; pharmacology ; Arsenicals ; pharmacology ; Cell Differentiation ; drug effects ; Cell Line, Tumor ; Cyclic AMP ; analogs & derivatives ; pharmacology ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; Drug Synergism ; Humans ; Leukemia, Promyelocytic, Acute ; pathology ; Oxides ; pharmacology ; Thionucleotides ; pharmacology ; Tretinoin ; pharmacology