In the cultural construction of independent institute,there exist the contradiction between tradition and innovation,cultural conflicts between private enterprises and the university.Therefore,adhering to the people-centered concept,coordinating tradition and innovation,merging the advantages of university culture and private enterprises culture into a whole,cultivating the unique spiritual culture,harmonious system culture and unified material culture of independent institute,forming the distinctive “Institute Culture” with its own cultural tradition will provide reference for the theory and practice to enrich and improve the connotative development of independent institute.

Objective - （ ） To analyze the epidemiological characteristics of occupational noise induced deafness ONID （ ） diagnosed by Guangdong Province Hospital of Occupational Disease Prevention and Control GDHOD from 2016 to 2020 and - Methods the reasons non ONID diagnosis. The data of ONID patients diagnosed in GDHOD from 2016 to 2020 were collected “ from the Occupational Disease Report Card in the Occupational Disease and Occupational Health Information Monitoring ” “ ” - System subsystem of the China Disease Prevention and Control Information System . The data of non ONID subjects were ， collected from the occupational disease diagnosis archives in the same hospital and the relevant data were analyzed Results ， ， （ ） retrospectively. Of the 1 432 subjects 824 subjects were diagnosed as ONID patients mainly of mild ONID 86.0% . （M） ， M Male patients accounted for 88.0%. The median of diagnosis age was 45.0 years old and of length of employment of ， ， ， diagnosis was 8.3 years. ONID patients were mainly found in Zhongshan Dongguan Zhuhai Jiangmen and Guangzhou City in ， ， （ ） the Pearl River Delta accounting for 67.6%. The cases distributed in 519 enterprises mainly on manufacturing 90.2% . ， - ， ； Among the 139 enterprises each enterprise had 2 11 patients worked within five years accounting for 53.9% 91.1% of the -， - - - ONID patients were distributed in large medium and small enterprises. ONID patients mainly worked in non public enterprises that accounted for 91.3%. There were 606 subjects could not be diagnosed as ONID. The main reasons for not being （ ）， diagnosed were that the weighted value of better ear hearing threshold was less than 26 dB 34.8% the working history of （ ）， occupational noise exposure was less than three years 31.5% the weighted value of better ear hearing threshold was less thanConclusion 26 dB and the average hearing threshold of binaural high frequency was less than 40 dB 16.2% . The ONID ， ， -， - patients have the characteristics of group aggregation. The Pearl River Delta manufacturing industry large medium and - - ： small non public enterprises are the key points of ONID prevention. The main reasons for not being diagnosed as ONID were ， the working history of occupational noise exposure was less than three years the weighted value of better ear hearing threshold ， - was less than 26 dB and the average high frequency hearing threshold of both ears was less than 40 dB.

The deubiquitinating enzyme ubiquitin specific peptidase 15 (USP15) is regarded as a regulator of TGFβ signaling pathway. This process depends on Smad7, the inhibitory factor of the TGFβ signal, and type I TGFβ receptor (TβR-I), one of the receptors of TGFβ. The expression level of USP15 seems to play vital roles in the pathogenesis of many neoplasms, but so far there has been no report about USP15 in psoriasis. In this study, immunohistochemical staining of USP15, TβR-I and Smad7 was performed in 30 paraffin-embedded psoriasis specimens and 10 normal specimens to investigate the expression of USP15, TβR-I and Smad7 in psoriasis and to explore the relevance among them. And USP15 small interfering RNA (USP15 siRNA) was used to transfect Hacat cells to detect the mRNA expression of TβR-I and Smad7. Of 30 cases of psoriasis in active stage, 28, 24 and 26 cases were positive for USP15, TβR-I and Smad7 staining, respectively. The positive rates of USP15 and Smad7 were significantly higher in psoriasis specimens than in normal skin specimens (44.1%±26.0% vs. 6.1%±6.6%, 47.2%±27.1% vs. 6.6%±7.1%), and positive rate of TβR-I (20.3%±22.2%) in psoriasis was lower than that in normal skin specimens (46.7%±18.2%). There was a significant positive correlation between USP15 and Smad7 expression, and significant negative correlations between USP15 and TβR-expression, an I d between TβR- and Smad7 expression I in psoriasis. After transfection of USP15 siRNA in Hacat cells, the expression of TβR-mRNA was up I -regulated and that of Smad7 was down-regulated. It is concluded that USP15 may play a role in the pathogenesis of psoriasis through regulating the TβR-I/Smad7 pathway and there may be other cell signaling pathways interacting with USP15 to take part in the development of psoriasis.

Background and Objective:The basic structure of salicylaldehydeamino acid Schiff base compounds includes a C=N chemical bond.These compounds show significant antitumor activities in vitro when combined with a metal ion.This study investigated the effects and possible mechanisms of four salicylaldehyde-amino acid Schiff base copper ternary coordination compounds on the proliferation of human gastric cancer cell line BGC823.Methods:The BGC823 cells were treated with the four compounds(6B,7B,6P,and 7P).Cell proliferation was detected by MTT assay.Apoptosis and changes in the cell cycle were analyzed by flow cytometry.DNA damage was observed using a DNA ladder assay.The expression of p53 protein was determined by immunocytochemistry.Results:The proliferation of BGC823 cells was significantly inhibited by the four compounds and the effect was concentrationdependent.The half maximal inhibitory concentration(IC_(50))of 6B,7B,6P,and 7P for BGC823 cells were 18.10,27.50,3.61,and 3.45 μmol/L,respectively.Flow cytometry showed the four drugs induced apoptosis in BGC823 cells,which was confirmed by DNA ladder experiments.Flow cytometry also detected changed phases in the cell cycle from treatment with the compounds.The percent of cells in the G_0/G_1 phase decreased and that of cells in the G_1/S and G_2/M phases increased,indicating that S-and G_2-phase blockages exist.As shown by immunocytochemistry,the expression of p53 decreased in BGC823 cells treated with the four drugs.indicating the involvement of the p53 pathway to BGC823 cell apoptosis.Conclusions:The four compounds showed significant activities on restraining proliferation of BGC823 cells in vitro,induced apoptosis,and caused changes in the cell cycle.This may be related to the downregulation of p53.

The medicinal fungi, which are of great importance in traditional medicine, are facing the problems of wild resources scarcity and low concentration of bioactive compounds. Velvet family and LaeA global regulator play a vital role in secondary metabolism and developmental programs, which are found in a wide variety of fungi ranging from Chytridiomycota to Basidiomycota. This review elaborates the structures and functions between Velvet family and LaeA protein. The Velvet family which shares the Velvet protein domain, including VeA (Velvet), VelB (Velvet like B), VosA (viability of spores A) and VelC (Velvet like C), acts on the regulation function is secondary metabolism and developmental programs such as asexual and sexual development. Furthermore, the function is affected by environmental factors such as light and temperature. LaeA protein which owns S-adenosylmethionine-dependent methyltransferase domain, coordinately regulates development and secondary metabolism by regulating and modifying the Velvet proteins. The regulation of LaeA is mediated by light receptor proteins. Therefore, clarifying the mechanism of Velvet and LaeA proteins in medicinal fungi will pave the way for nurturing medicinal fungi and improving production of bioactive compounds.
Fungal Proteins ; metabolism ; Fungi ; chemistry ; Gene Expression Regulation, Fungal ; Genes, Regulator ; Protein Structure, Tertiary ; Secondary Metabolism ; Structure-Activity Relationship

BACKGROUND AND OBJECTIVEThe basic structure of salicylaldehyde-amino acid Schiff base compounds includes a C=N chemical bond. These compounds show significant antitumor activities in vitro when combined with a metal ion. This study investigated the effects and possible mechanisms of four salicylaldehyde-amino acid Schiff base copper ternary coordination compounds on the proliferation of human gastric cancer cell line BGC823.

METHODSThe BGC823 cells were treated with the four compounds (6B, 7B, 6P, and 7P). Cell proliferation was detected by MTT assay. Apoptosis and changes in the cell cycle were analyzed by flow cytometry. DNA damage was observed using a DNA ladder assay. The expression of p53 protein was determined by immunocytochemistry.

RESULTSThe proliferation of BGC823 cells was significantly inhibited by the four compounds and the effect was concentration-dependent. The half maximal inhibitory concentration (IC50) of 6B, 7B, 6P, and 7P for BGC823 cells were 18.10, 27.50, 3.61, and 3.45 micromol/L, respectively. Flow cytometry showed the four drugs induced apoptosis in BGC823 cells, which was confirmed by DNA ladder experiments. Flow cytometry also detected changed phases in the cell cycle from treatment with the compounds. The percent of cells in the G(0)/G(1) phase decreased and that of cells in the G1/S and G(2)/M phases increased, indicating that S-and G2-phase blockages exist. As shown by immunocytochemistry, the expression of p53 decreased in BGC823 cells treated with the four drugs, indicating the involvement of the p53 pathway to BGC823 cell apoptosis.

CONCLUSIONSThe four compounds showed significant activities on restraining proliferation of BGC823 cells in vitro, induced apoptosis, and caused changes in the cell cycle. This may be related to the downregulation of p53.

Aldehydes ; chemistry ; Amino Acids ; chemistry ; Antineoplastic Agents ; chemical synthesis ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Coordination Complexes ; chemical synthesis ; pharmacology ; Copper ; chemistry ; Humans ; Inhibitory Concentration 50 ; Schiff Bases ; chemistry ; Stomach Neoplasms ; metabolism ; pathology ; Tumor Suppressor Protein p53 ; metabolism

Objective To study the role of fibulin-5 in urothelial carcinoma of bladder. Methods Fibulin-5 expression was detected in bladder cancer tissues (13 cases of G_1 and G_2, 7 cases of G_3) and normal bladder mucosa samples by Western blotting assay. Fibulin-5 cDNA was amplified by PCR and cloned into pMD-19T simple vector. The pMD-19T-Fibulin-5 vector was digested by restriction endonucleases XhoI and EcoRI to generate a XhoI-Fibulin5-EcoRI fragment that was then ligated into the identical sites in p-EGFP-Nl plasmid to synthesize p-EGFP-Fibulin-5 plasmid. The p-EGFP-Fibulin-5 plasmid was finally transfected into bladder cancer cell line 5637. The migration and invasion of untransfected, vector-transfected and fibulin-5-transfected bladder cancer cells were measured by Boyden chamber assay. Results Compared to 1. 16 ±0. 28 in the normal control, the expression of fibulin-5 protein in low grade and high grade tumors were 0. 57±0. 32 and 0. 44±0. 42(P<0. 01, respectively). However, the difference between low grade and high grade tumors was not statistically significant (P>0. 05). The successfully transfected bladder cancer cells demonstrated green fluorescent light. The migrated cell number of fibulin-5-transfected cells was 127. 6 ± 3. 1 compared with 139. 3±7. 7 for vector-transfected cells and 136. 9±5. 7 for untransfected cells (P>0. 05, respectively). In contrast, the invaded cell number of fibulin-5-transfected cells was 8. 0±3. 1 compared with 31. 5±4. 8 for vector-transfected cells and 31. 7±4. 7 for untransfected cells (P<0. 01, respectively). Conclusion Fibulin-5 is down-regulated in urothelial carcinoma of bladder and acts as a tumor suppressor gene by inhibiting the invasion of bladder cancer cells.

BACKGROUNDbevacizumab is a humanized recombinant vascular endothelial growth factor (VEGF) monoclonal antibody, which specifically binds to VEGF and inhibits tumor cell growth, proliferation and metastasis. We aimed to investigate the safety and pharmacokinetics of bevacizumab in Chinese patients with advanced cancer.

METHODSThirty-nine Chinese patients with metastatic or relapsed cancers who failed prior therapy were enrolled in this phase I study of bevacizumab. Bevacizumab was infused by a calculated pump at doses from 5 mg/kg to 15 mg/kg in 90 minutes. Patients underwent serial pharmacokinetic evaluations. Patients that received at least one infusion of bevacizumab were included in the safety study.

RESULTSThirty-five patients finished all 5 infusions following protocol. One patient withdrew after 3 infusions due to grade 3 proteinuria. Common adverse events possibly related to the study drug were proteinuria (17/39, 43.6%), hypertension (13/39, 33.3%), gingival bleeding (7/39, 17.9%), epistaxis (6/39, 15.4%), pharyngeal inflammation (6/39, 15.4%), fatigue (6/39, 15.4%) and stomatitis (4/39, 10.3%). Bevacizumab pharmacokinetics was linear within the range of 5 mg/kg q2w--10 mg/kg q2w and 15 mg/kg q3w. CL (clearance), Vd (volume of distribution at elimination) and Vss (volume of distribution at steady state) were similar after single and multiple doses at 5, 10 and 15 mg/kg.

CONCLUSIONSBevacizumab is well tolerated in Chinese patients. No unexpected adverse events were observed. There is no racial difference in the pharmacokinetics.

Adult ; Aged ; Angiogenesis Inhibitors ; adverse effects ; pharmacokinetics ; therapeutic use ; Antibodies, Monoclonal ; adverse effects ; pharmacokinetics ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Asian Continental Ancestry Group ; Bevacizumab ; Female ; Humans ; Male ; Middle Aged ; Neoplasms ; drug therapy

OBJECTIVETo investigate an effective purification method for removing endotoxin from Prevotella intermedia.

METHODSThe main protein ingredients of bacteria prepared from ammonium sulfate precipitation were further treated with octyl phenyl polyoxyethylene ether (Triton X-114), and then processed at 4°C, 37°C and 25°C. The obtained aqueous phase after at least two more cycle repeated operations was assayed for endotoxin by Western blotting, LAL-clotting method, in vitro cell stimulation and in vivo animal experiments.

RESULTSWestern blotting and LAL-clotting method demonstrated that the reduction in endotoxin level was greater than 99.99% and recovery of the proteins after endotoxin removal was greater than 90% with Triton X-114 treatment for 3 cycles. The cytokines expression level was lower in both in vitro cell stimulation and in vivo animal experiments than in untreated group (P < 0.05).

CONCLUSIONSThe extraction method provides a new choice for endotoxin removal from large volumes of the oral Prevotella intermedia.

Animals ; Bacterial Proteins ; isolation & purification ; Endotoxins ; isolation & purification ; Female ; HEK293 Cells ; Humans ; Interleukin-1alpha ; blood ; Interleukin-6 ; blood ; Interleukin-8 ; metabolism ; Lipopolysaccharides ; pharmacology ; Mice ; Mice, Inbred C57BL ; Polyethylene Glycols ; chemistry ; Prevotella intermedia ; chemistry ; metabolism ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo re-confirm and characterize the biophysical and pharmacological properties of endogenously expressed human acid-sensing ion channel 1a (hASIC1a) current in HEK293 cells with a modified perfusion methods.

METHODSWith cell floating method, which is separating the cultured cell from coverslip and putting the cell in front of perfusion tubing, whole cell patch clamp technique was used to record hASIC1a currents evoked by low pH external solution.

RESULTSUsing cell floating method, the amplitude of hASIC1a currents activated by pH 5.0 in HEK293 cells is twice as large as that by the conventional method where the cells remain attached to coverslip. The time to reach peak at two different recording conditions is (21+/-5) ms and (270+/-25) ms, respectively. Inactivation time constants are (496+/-23) ms and (2284+/-120) ms, respectively. The cell floating method significantly increases the amiloride potency of block on hASIC1a [IC50 is (3.4+/-1.1) micromol/L and (2.4+/- 0.9) micromol/L, respectively]. Both recording methods have similar pH activation EC50 (6.6+/-0.6, 6.6+/-0.7, respectively).

CONCLUSIONASICs channel activation requires fast exchange of extracellular solution with the different pH values. With cell floating method, the presence of hASIC1a current was re-confirmed and the biophysical and pharmacological properties of hASIC1a channel in HEK293 cells were precisely characterized. This method could be used to study all ASICs and other ligand-gated channels that require fast extracellular solution exchange.

Acid Sensing Ion Channels ; Amiloride ; pharmacology ; Biophysics ; instrumentation ; methods ; Cell Culture Techniques ; instrumentation ; methods ; Cell Line ; Cell Membrane ; chemistry ; drug effects ; metabolism ; Culture Media ; chemistry ; pharmacology ; Extracellular Fluid ; chemistry ; metabolism ; Humans ; Hydrogen-Ion Concentration ; drug effects ; Membrane Potentials ; drug effects ; physiology ; Nerve Tissue Proteins ; chemistry ; drug effects ; metabolism ; Neuropharmacology ; instrumentation ; methods ; Patch-Clamp Techniques ; instrumentation ; methods ; Perfusion ; instrumentation ; methods ; Sodium Channel Blockers ; pharmacology ; Sodium Channels ; chemistry ; drug effects ; metabolism ; Time Factors