Analysis of the synergistic effect of triptolide combined with gefitinib on EGFR-mutant NSCLC cells / 中国药房

OBJECTIVE To investigate the synergistic effect of triptolide （TPL） combined with epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI） gefitinib on EGFR-mutated non-small cell lung cancer （NSCLC） cells and its potential mechanism. METHODS Human NSCLC cell lines H1975 （EGFR T790M/L858R mutated drug-resistant cell lines） and H1299 （EGFR wild-type non-drug-resistant cell lines） were cultured in vitro. MTT method was used to detect cell activity， and the effect of combined medication was evaluated by the combination index （CI）. The H1975 cells were divided into blank group， low- concentration and high-concentration groups of TPL （5 nmol/L or 15 nmol/L）， gefitinib group （2 μmol/L）， low-concentration and high-concentration groups of TPL+gefitinib （5 nmol/L TPL+2 μmol/L gefitinib， 15 nmol/L TPL+2 μmol/L gefitinib）. Flow cytometry was used to detect the apoptosis of H1975 cells and the distribution of the cell cycle. Molecular docking studies were used to predict the binding ability of TPL to EGFR. The expressions of phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） pathway and autophagy-related proteins [microtubule-associated protein 1 light chain 3α （MAP1LC3A）， MAP1LC3B] in H1975 cells were detected by flow cytometry. RESULTS TPL had a strong inhibitory effect on the proliferation of H1975 and H1299 cells in a time-dependent and dose-dependent manner. Forty-eight hours treatment of 5 or 15 nmol/L TPL combined with gefitinib had a synergistic inhibitory effect on the proliferation of H1975 cells （CI＜1）， while there was no synergistic inhibitory effect on H1299 cells （CI＞1）. Compared with the blank group， the apoptosis rate and the proportion of H1975 cells at G0/G1 phase were increased significantly in administration groups， while the proportions of cells at S phase and G2/M phase （except for several TPL groups） were decreased significantly， and the combination group had better effects （P＜0.05）. Molecular docking studies showed that the hydroxyl radical of TPL could form hydrogen bonds with the Thr854 residue of the product encoded by EGFR T790M/L858R mutation. Compared with the blank group， the expressions of pathway-related proteins were down-regulated significantly in administration groups， while those of autophagy-related proteins were up-regulated significantly， and the combination group had better effects （P＜0.05）. CONCLUSIONS TPL combined with gefitinib can synergically inhibit the proliferation activity of EGFR-mutated NSCLC cells， the mechanism of which may be related to the down-regulation of PI3K/Akt/ mTOR pathway and induction of autophagy.

Anatomic characteristics of the lacrimal sac in the nasal cavity of recurrent dacryocystitis and its application in endoscopic dacryocystorhinostomy combined with stent implantation / 解剖学报

Objective To observe the efficacy of endoscopic nasal dacryocystoma anastomosis combined with stent implantation in the treatment of chronic recurrent dacryocystitis. Methods Thirty patients (30 eyes) with chronic dacryocystitis who had relapsed after traditional endoscopic nasal dacryocystorhinostomy were hospitalized in the Department of Otolaryngology Head and Neck Surgery department of Gansu Provincial People's Hospital from January 2010 to January 2019. Nasal lacrimal anastomosis under endoscope, intraoperative combined stent implantation, 3 months after operation, the lacrimal duct stent was removed, the patient ' s tearing symptoms were observed, the lacrimal duct was flushed to determine the lacrimal duct obstruction, and the follow-up period was 12 months. Results Twelve months of follow-up to 12 months, 14 eyes of 30 patients had no complaints of tearing, tearing, and lacrimal tract flushing; The ostomy fistula was unobstructed under nasal endoscope and the fistula was not significantly reduced. There was no complaint of tears in the eyes, tears overflowed, and the lacrimal duct was flushed, but the fistula opening was reduced.; Four eyes showed granulation hyperplasia next to the fistula, which blocked the fistula again. The overall effective rate was 87%. Conclusion Endoscopic dacryocystorhinostomy combined with stent implantation is an effective method for the treatment of chronic recurrent dacryocystitis with good clinical result.

Correlations between alterations of T-helper 17 cells and treatment efficacy after concurrent radiochemotherapy in locally advanced cervical cancer (stage IIB-IIIB): a 3-year prospective study / 中华医学杂志(英文版)

BACKGROUND@#Recently, T-helper 17 (Th17) cells have been proved to play an important role in promoting cervical cancer. But, till now, few study has been carried out to understand the involvement of these cells in efficacy of anti-tumor treatments. This study aimed to investigate the alterations in the percentage of circulating Th17 cells and related cytokines in locally advanced cervical cancer (LACC) patients before and after concurrent chemoradiotherapy (cCRT) and to analyze the correlations between the alterations in Th17 cells and treatment efficacy.@*METHODS@#A prospective study with 49 LACC (International federation of gynecology and obstetrics [FIGO] stage IIB-IIIB) patients and 23 controls was conducted. Patients received the same cCRT schedule and were followed up for 3 years. Circulating Th17 cells (CD3+CD8- interleukin [IL]-17+ T cells) and related cytokines IL-17, transforming growth factor-β (TGF-β), IL-10, IL-23, IL-6, and IL-22 were detected before and after cCRT. Correlations between alterations of circulating Th17 cells and treatment efficacy were analyzed. Kaplan-Meier analysis was used for overall survival (OS) and progression-free survival (PFS).@*RESULTS@#We found that 40 patients finished the entire cCRT schedule and met the endpoint of this study. The percentage of circulating Th17 cells in the LACC patients was higher than that in the controls, and it significantly decreased after cCRT (P < 0.05). After cCRT, patients were divided into two groups based on the average of the Th17 cells declined. The subgroup of patients with a prominent decrease in circulating Th17 cells after cCRT had a higher treatment efficacy and longer PFS and OS times. Compared with the control patients, LACC patients had higher IL-6, IL-10, IL-22, TGF-β levels and a lower IL-23 level (P < 0.05). After cCRT, IL-6, IL-10, IL-17, IL-23 level significantly increased and TGF-β level significantly decreased compared with the levels before cCRT (P < 0.05).@*CONCLUSION@#Circulating Th17 cells in the LACC patients (FIGO stage IIB-IIIB) were higher than those in the controls, but they generally decreased after cCRT. A more pronounced decrease in circulating Th17 cells after cCRT was correlated with better therapeutic effect and longer PFS and OS times.

Application of upper arm totally implantable venous access ports in 34 patients with tumor / 中华临床营养杂志

Objective To investigate the safety,feasibility and clinical application effect of upper arm totally implantable venous access port (TIVAP) inserted by the combination of oncologists and nurses in patients with tumor.Methods A total of 34 patients,who needed long-term transfusion treatment,were included in this study with upper arm TIVAP from March 2017 and December 2017.There were 20 males and 14 females.The median age was 63 (35 ～ 83) years.Upper arm TIVAP was implanted by both doctors and nurses into the patients with tumor,and the TIVAP related success rate,complications and patients satisfaction were recorded.Results 34 patients all succeeded in TIVAP implantation with the operation success rate of 100％.The average operation time was about 40 minutes (30 to 60 minutes) from the disinfecting cloth to the end of the suture.The operations of all patients were successful.After the operation two patients died of cancer progression,one patient had soft tissue infection around capsular bag,None of the patients had other complications such as blocked infusion,catheter shift,port reversal,and so on,and the incidence of complication was 2.94％ (1/34).Conclusions Upper arm TIVAP has the advantages of safe puncture,shorter operation time,few intra-operative and post-operative complications and higher feasibility for operation by both oncologist and nurse,which can supplement the limitations and deficiencies of the chest wall port and PICC in a certain extent,therefore is a good choice for clinical application.

Application of nursing intervention based on transtheoretical model and stages of change in breastfeeding for primiparas / 中国实用护理杂志

Objective To explore the effect of nursing intervention based on the transtheoretical model and stages of change on breastfeeding knowledge, self-efficacy, and duration of breastfeeding in newly born pregnant women, aimed to provide reference for breastfeeding behavior health education model for pregnant women. Methods The 130 primiparas who came to the hospital graded a class- three of Shanxi Province for perinatal examination were selected as the research subjects from May to June in 2017 , they were divided into test group and control group by random digits table method. In the control group, the normal breastfeeding health guidance was carried out in the three stages of prenatal, hospitalized and after discharge. The test group divided the primipara from the beginning of pregnancy to 6th months postpartum period into 5 stages according to transtheoretical model and stages of change. The new strategy of breastfeeding should be formulated and implemented according to different stages and behavior changing processes. Results The total score of breastfeeding knowledge of primipara were (8.76±1.14), (8.92±1.21), (9.90±1.27), (9.94±1.29) points in control group before intervention, the 3rd day, the 42nd day and the 6th month after delivery, and they were (9.11 ± 1.42), (12.02 ± 1.64), (13.04 ± 1.67), (15.00±1.83) points respectively in test group, the differences were statistically significant(Ftime= 51.823, Fgroup=10.406, Finteractive=56.641, all P < 0.05). The total scores of breastfeeding self-efficacy of primipara were (84.62 ± 1.14), (88.96 ± 1.41), (86.65 ± 1.47), (84.31 ± 1.57) points respectively in control group before intervention, the 3rd day, the 42nd day and the 6th month after delivery, while in test group they were (84.98 ± 1.20), (104.02 ± 1.42), (111.00 ± 1.45), (120.04 ± 1.40) points, the differences were statistically significan (Ftime=12.592, Fgroup=229.674, Finteractive=79.955, all P<0.05). The pure breastfeeding rates of primipara were 60.0％(33/55) , 41.8％(23/55), 21.8％(12/55) in control group on the 3rd day, the 42nd day and the 6th month after delivery, they were 84.7％(50/59), 76.3％(45/59) , 49.2％(29/59) in the test group. The differences was statistically significant (χ2=8.804, 14.038, 9.235, all P <0.01). Conclusion Breastfeeding intervention based on the theory of behavioral staged transition can help primipara to improve breastfeeding knowledge and self-efficacy, and improve breastfeeding status.

Relationship between DNMT1 and Methylation of SHP-1 Promoter 2 in K562 Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the relationship of DNA methyltransferase 1 ( DNMT1 ) with hematopoietic cell phosphatase (SHP-1) gene expression and promoter 2 methylation status in cell line K562.</p><p><b>METHODS</b>The promoter sequence of SHP-1 gene promoter 2 in NCBI database was analyzed, the K562 cells were transfected with the lentiviral plasmids-the specified retroviral vector psiHIV-mU6-shDNMT1 and psiHIV-mU6-mcherryFP-control. The methylation status of SHP-1 gene promoter 2 in K562 cells was detected by methylation-specific polymerase chain reaction (MSP) and bisulfite-modified sequencing (BSP). Western blot was used to detect the protein expression level of SHP-1 and DNMT1, the SYBR Green fluorescence quantitative PCR was used to detect the expression of SHP-1 mRNA.</p><p><b>RESULTS</b>It was found that the promoter 2 of SHP-1 gene located between -577 bp to +300 bp, and 22 CpG sites contained between -353 bp-+182 bp were aberrantly hypermethylated and the SHP-1 could not be detected in K562 cells. In vitro, the detection demonstrated that the expression level of DNMT1 in K562 cells transfected with psiHIV-mU6-shDNMT1 was 0.48±0.06 significantly lower than that of psiHIV-mU6-control group (1.33±0.19)(t= 4.18, P<0.05). The expression of SHP-1 mRNA in K562 cells transfected with psiHIV-mU6-shDNMT1 was significantly higher than that in K562 cells transfected with psiHIV-mU6-shDNMT1 (14.23±3.83 vs 1.031±0.156)(P<0.01). DNMT1 silencing induced demethylation of the 22 CpG sites located in the SHP-1 promoter 2, and SHP-1 gene was re-expression in K562 cells.</p><p><b>CONCLUSION</b>The DNMT1 in K562 cells relates with the hypermethylation and silencing of SHP-1 promoter in K562 cells.</p>

Danggui Buxue Decoction total glycosides combined with Hirudo in the treatment of pulmonary fibrosis in rats / 中成药

AIM To study the effects of Danggui Buxue Decoction total glycosides combined with Hirudo in the treatment of pulmonary fibrosis in rats and its mechanism.METHODS One hundred and twenty male SD rats were selected,eighteen of which were taken as normal group (normal saline),the remaining 102 rats were used to establish model for pulmonary fibrosis.Seventy-two modeled rats were randomly divided into model group (normal saline),Danggui Buxue Decoction total glycosides group (13 mg/kg),Hirudo group (Hirudo powder,4 g/kg) and combination group (Danggui Buxue Decoction total glycosides,13 mg/kg;Hirudo powder,4 g/kg),eighteen rats in each group with intragastric administration.RESULTS On the 7th,14th and 28th days after modeling,alveolar inflammatory score,pulmonary fibrosis degree score,TGF-β1 and PAI-1 expression levels in lung tissue,IL-4 and IL-17 expression levels in alveolar lavage fluid,hydroxyproline (HYP) content in lung tissue in the model group were significantly higher than those in the normal group (P ＜ 0.05).Alveolar inflammatory score,pulmonary fibrosis degree score,TGF-β1,PAI-1,IL-4,IL-17 expression levels and HYP content in the Danggui Buxue Decoction total glycosides group,Hirudo group and combination group were significantly lower than those in the model group (P ＜ 0.05).In the combination group,alveolar inflammatory score,pulmonary fibrosis degree score,TGF-β1,PAI-1,IL-4,IL-17 expression levels and HYP content were significantly lower than those in the Danggui Buxue Decoction total glycosides group and Hirudo group (P ＜ 0.05).CONCLUSION Danggui Buxue Decoction total glycosides combined with Hirudo have good therapeutic effects on pulmonary fibrosis in rats mainly by reducing TGF-β1,PAI-1 expression levels and HYP coment in lung tissue.

Stem cells in the skin regeneration and wound healing：problem and perspective / 中国组织工程研究

BACKGROUND:Present treatments for chronic skin wounds have certain limitations, and adult stem cels play a potentialpart in cutaneous repair and regeneration. OBJECTIVE:To review effects of stem cels in skin regeneration and wound healing. METHODS:The first author retrieved CNKI and Medline databases by computer for relevant articles published from 2000 to 2010. Thekeywords were “epidermal stem cels, hair folicle stem cels, stem cels, transplantation, dermal stem cels” in Chinese and in English, respectively. Then totaly 489 papers were obtained after initial survey, and according to the inclusion criteria, 30articles were selected for review. RESULTS AND CONCLUSION:Epidermal stem cels and other adult stem celshave beenapplied to treat wounds and other skin diseases. Epidermal stem celsarethe crucialcelsource of skin development, repairandremodeling.Epidermal stem celsarealwaysina resting statein vivo.Unless,skin injure or culturein vitro, celdivision and proliferation wilbe significantly fastened. The stability of the epidermis mainly dependson the asymmetric divisionof a subpopulation, in which two daughter celsare produced, including one with characteristics of stem cels, and the other differentiated into transient amplifying cels that wil be differentiated intopost mitotic celsafter a series of cel divisions (3-5 times). Afterwards, those post mitotic celsaredeveloped into terminal differentiation cels onthe basal layer, finaly detachfromthe epidermisasdander. In addition, it is unclear whether epidermal factors are related to apoptosis, migration and differentiation in the process of wound repairandeven under physiological conditions. Therefore, application ofstem celsinwound healing requiresa further discussion.

Randomized study of Hemp seed pill plus lactulose oral solution regimen combination in the treatment of constipation induced by morphine-type drugs / 中国生化药物杂志

Objective To observe the efficacy in combination with Hemp seed pill and lactulose oral solution for treating cancer pafients with constipation induced by morphine-type drugs.Methods 62 Cancer patients with constipation induced by morphine-type drugs diagnosed by pathology or cytology were collected from January 2013 to July 2016 in Suzhou BenQ hospital for this study.The patients in study group received both Hemp seed pill and lactulose oral solution, and patients in control group received lactulose oral solution only.After treatment for 3 weeks,some indexes were observed, including outcomes in the overall response rates, Karnofsky score, weight.Results The total effective rate of the study group was higher than the control group(77.4%vs 48.3%, P<0.05), the difference was statistically significant;After treatment,Karnofsky score and the percentage of patients gaining weight in study group were markedly higher than those in control group,the difference was statistically significant(P<0.05).Conclusion Hemp seed pill combined with lactulose oral solution has a good clinical efficacy in treating pafients with constipation induced by morphine-type drugs, and can improve patient's quality of life.

Overexpression of SHP-1 Enhances the Sensitivity of K562 Cells to Imatinib / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of overexpression of SH2-containing tyrosine phosphatase 1 (SHP-1) on sensitivity of chronic myelogenous 1eukemia (CML) K562 cell line to imatinib and its related mechamism.</p><p><b>METHODS</b>K562 cells were infected with the lentiviral plasmids containing the specified retroviral vector (pEX-SHP-1-puro-Lv105) or the mock vector (pEX-EGFP-puro-Lv105). The expression of SHP-1 in K562 cells treated with 0.2 µmol/L imatinib (IM) for 72 h was determined by Western blot. After transfection the CCK-8 assay was used to determine the proliferation of the tramfected K562 cells (K562(SHP-1) and K562(EGFP) cells) at 72 h after exposure to different doses of IM, the half inhibitary concentration (IC50) was calculated. The mechanisms of the overexpression effects of SHP-1 and IM on the proliferation in K562 cells was investigated, the BCR-ABL1 activity and the level of tyrosine phosphorylation of CrkL (pCrkL) was measured by flow cytometry; the Western blot was used to detect the expression and activity of these molecules controlling cell growth, including MAPK, AKT, STAT5 and JAK2.</p><p><b>RESULTS</b>After exposure of K562 cells to 0.08 µmol/L IM for 72 h, there was no significant change of SHP-1 expression in K562 cells. After exposure to 0.2 µmol/L of IM for 72 h, the inhibitory rate of K562(SHP-1) group was higher than that of K562(EGFP) group (P < 0.05), indicating that overexpression of SHP-1 in K562 cells could enhance the proliferation inhtibition effect of IM on K562 cells. The IC50 of IM in K562(SHP-1) cells was the lower as compared with that of K562(EGFP) cells (P < 0.05) after exposure to different concentrations of IM for 72 h. The slope of K562(SHP-1) cells was the largest ranging 0.02 - 0.16 µmol/L of IM. Overexpression of SHP-1 and IM could inhibit the activity BCR-ABL1, MAPK, AKT, STAT5 and JAK2 signaling pathways in the K562 cell line and displayed a synergistic effect.</p><p><b>CONCLUSION</b>SHP-1 inhibits BCR-ABL1, MAPK, AKT, STAT5 and JAK2 signaling pathways in K562 cells, the overexpression of SHP-1 can enhance the sensitivity of K562 cells to IM.</p>

Expression and Clinical Significance of DNMT in Patients with Chronic Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression and clinical significance of DNA methyltransferases (DNMT) mRNA in patients with chronic myeloid leukemia (CML).</p><p><b>METHODS</b>The expression levels of DNMT mRNA in mononucllear cells (MNC) of bone marrow or in peripheral blood of 93 CML patients in 3 different phases and 10 normal controls (NC) were detected by SYBR Green flurescent quatitative PCR.</p><p><b>RESULTS</b>The relative expression levels of DNMT1 mRNA in NC, chronic phase CML (CML-CP), accelerated phase (CML-AP) and blastic phase (CML-BP) were 1.45 ± 0.22, 1.83 ± 0.63, 2.95 ± 0.87 and 3.24 ± 1.39 resectively. The expression of DNMT1 mRNA showed no statistically significant difference between CML-CP and NC (P = 0.28). The expression of DNMT1 mRNA in advanced stages (including CML-AP and CML-BP) of CML obviously increased in comparison with CML-CP and NC (P < 0.05). The expression of DNMT1 mRNA in CML-AP was not significantly different from that in CML-BP (P = 0.336). The relative expression levels of DNMT3a mRNA in NC, CML-CP, CML-AP and CML-BP groups were 1.29 ± 0.34, 1.34 ± 0.46, 2.33 ± 1.05 and 3.18 ± 1.23 resectively. And the expression levels of DNMT3a mRNA were not statistically significantly different between CML-CP and NC (P = 0.844). The results showed that the expression of DNMT3a mRNA in the advanced phase of CML significantly increased in comparison with that in CML-CP and NC (P < 0.05). Meanwhile, the expression of DNMT3a mRNA in CML-AP was not different from that in CML-BP (P = 0.304). The relative expression levels of DNMT3b mRNA in NC, CML-CP, CML-AP and CML-BP groups were 1.37 ± 0.31, 16.41 ± 22.50, 9.36 ± 5.50 and 12.17 ± 13.44 resectively. It was also found that the level of DNMT3b mRNA in CML significantly increased in comparison with NC (P < 0.05), and that the between the 3 different phase of CML was not statistically significantly different (P >0.05).</p><p><b>CONCLUSION</b>The expression of DNMT mRNA increases in advanced CML as compared with normal controls and CML-CP, and the increased levels of DNMT mRNA probably correlate with disease progression in CML.</p>

The effect of rosiglitazone on expressions of IL-18, MCP-1 and MMP-9 in rabbits with atherosclerosis / 中国药学杂志

OBJECTIVE: To compare the effects of rosiglitazone and simvastatin on inflammatory factors in atherosclerotic rabbits and to explore the anti-atherosclerosis mechanism. METHODS: Thirty-six male New Zealand rabbits were randomly divided into four groups: control group, model group, simvastatin group, and rosiglitazone group. Subcutaneous injection of dl-homocyesteine thiolac-tone combined with high fat diet was used to reproduce atherosclerotic rabbit model, the serum level of interleukin-18 (IL-18) was examined by ELISA, and the expressions of monocyte chemoattractant-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) in aortic atherosclerotic plaque were examined by immunohistochemistry. RESULTS: Compared with the control group, the serum levels of IL-18 and the expressions of MMP-9 and MCP-1 in aortic atherosclerotic plaque were increased obviously in the other three groups (P0.05). CONCLUSION: Rosiglitazone can decrease the serum level of IL-18 and the expressions of MCP-1 and MMP-9 in aortic atherosclerotic plaque, and inhibit the development of atherosclerosis. The mechanism is related to anti-inflammation.

Analysis of the hereditary etiology of 336 patients with non-syndromic sensorineural hearing loss from Ningxia Hui Autonomous Region of China / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the molecular genetic causes and their characteristics of deafness in Ningxia province, we established screening of three common hereditary deafness genes in 336 deaf and hard-of-hearing patients in this district.</p><p><b>METHODS</b>Peripheral blood samples were obtained from a total of 336 patients with non-syndromic sensorineural hearing loss in parts of special education schools in Ningxia province to extract genomic DNA. The mitochondrial DNA 12S rRNA m.1555A > G mutation was screened by PCR Alw26I digestion and sequence analysis PCR and direct sequencing were used to analyze the coding region of GJB2 and exons 8 and 19 of SLC26A4. Statistical analysis was performed by using SPSS 11.0 software. Frequencies of different GJB2 or SLC26A4 mutations were compared between Han and Hui people.</p><p><b>RESULTS</b>Among these 336 patients, seven cases (2.08%, 7/336) were found to carry mtDNA 12S rRNA m.1555A > G homozygous mutation, 45 cases (13.39%) were caused by GJB2 mutations and 28 cases (8.33%) had two mutated alleles (homozygote and compound heterozygote) of SLC26A4. In detail, 16.67% (56/336) patients carried GJB2 mutations including 11 single mutant carriers. The allele frequency of c.235delC and c.299_300delAT were 9.52% (64/672) and 2.68% (18/672), respectively, making up 81.19% (82/101) of all pathogenic mutated alleles for GJB2. The single mutant allele carriers of SLC26A4 is 32, and two types (c.919-2A > G and c.2168A > G) accounted for 95.29% (24/27) mutations, totally. We also found that statistically significant differences in c.919-2A > G and c.2168A > G frequencies between Han and Hui people (c.919-2A > G, χ(2) = 8.229, P = 0.004; c.2168A > G, χ(2) = 5.277, P = 0.022). However, there was no statistically significant difference in GJB2 mutation between Han and Hui people.</p><p><b>CONCLUSIONS</b>GJB2 mutation was a primary cause for non-syndromic sensorineural hearing loss in Ningxia province, and c.235delC was the most common mutant forms of GJB2. c.919-2A > G and c.2168A > G were common mutant forms of SLC26A4, their frequencies were also statistically significant differences between Han and Hui people.</p>

Culture supernatants of breast cancer cell line MDA-MB-231 treated with parthenolide inhibit the proliferation, migration, and lumen formation capacity of human umbilical vein endothelial cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Parthenolide has been tested for anti-tumor activities, such as anti-proliferation and pro-apoptosis in recent studies. However, little is known about its role in the process of tumor angiogenesis. This study aims to investigate the effects and potential mechanisms of parthenolide on the proliferation, migration and lumen formation capacity of human umbilical vein endothelial cells.</p><p><b>METHODS</b>Different concentrations of parthenolide were applied to the human breast cancer cell line MDA-MB-231 cells. After 24-hour incubation, the culture supernatants were harvested and used to treat human umbilical vein endothelial cells for 24 hours. Then an inverted fluorescence phase contrast microscope was used to evaluate the human umbilical vein endothelial cells. The secretion of vascular endothelial growth factor (VEGF), interleukin (IL)-8 and matrix metalloproteinases (MMP)-9 in the culture supernatant of the MDA-MB-231 cells was then measured with enzyme-linked immunosorbent assay (ELISA) assays.</p><p><b>RESULTS</b>Suppression of proliferation, migration, and the lumen formation capacity of human umbilical vein endothelial cells was observed in the presence of the culture supernatants from the breast cancer cell line treated with different concentrations of parthenolide. Parthenolide decreased the levels of the angiogenic factors MMP-9, VEGF, and IL-8 secreted by the MDA-MB-231 cells.</p><p><b>CONCLUSIONS</b>Parthenolide may suppress angiogenesis through decreasing angiogenic factors secreted by breast cancer cells to interfere with the proliferation, migration and lumen-like structure formation of endothelial cells, thereby inhibiting tumor growth. It is a promising potential anti-angiogenic drug.</p>

Involvement of protein tyrosine kinases in β-amyloid protein-induced suppression of long-term potentiation in the rat hippocampal CA1 region in vivo / 生理学报

Although the impairing effects of beta-amyloid (Aβ) protein on synaptic plasticity and cognitive function have been widely reported, the mechanisms underlying the neurotoxicity of Aβ are still not well known. The present study observed the effects of intracerebroventricular (i.c.v.) injection of both Aβ(23-35) and genistein (a specific tyrosine kinase inhibitor at high concentration) on the hippocampal long-term potentiation (LTP) in the CA1 region, and investigated its possible protein tyrosine kinase (PTK) mechanism. Male Wistar rats were surgically prepared for acute LTP recordings in vivo. Two parallel bond electrodes for stimulating and recording were simultaneously inserted into the right hippocampus of rats. The field excitatory postsynaptic potentials (fEPSPs), paired-pulse facilitation (PPF) and high-frequency stimuli (HFS)-induced LTP were recorded by delivering test stimuli, paired pulses and HFS to the Schaffer-collateral/commissural pathway. The results showed that: (1) i.c.v. injection of Aβ(23-35) did not affect the baseline synaptic transmission, but significantly suppressed the HFS-induced LTP, with a decreased average amplitude of fEPSPs [(129.2+/-6.7)% in 10 nmol Aβ(23-35) group; (110.6+/-8.6)% in 20 nmol Aβ(23-35) group; P<0.01] at 1 h post-HFS when compared to that in the control group [(163.1+/-8.1)%]; (2) Similarly, i.c.v. injection of genistein (200 nmol) did not change the basic synaptic transmission, but significantly suppressed HFS-induced LTP, with the similar average amplitude of fEPSPs [(114.0+/-7.2)%] at 1 h post-HFS to that in 20 nmol Aβ(23-35) group; (3) Co-application of Aβ(23-35) (20 nmol) and genistein (200 nmol) caused no additive suppression of LTP, and the average amplitude of fEPSPs was (113.0+/-8.8)% at 1 h post-HFS, showing no significant difference when compared with that in Aβ(23-35) or genistein alone groups (P>0.05); (4) There was no significant change in the PPF following genistein and Aβ(23-35) alone or co-injection (P>0.05). These experimental results indicate that i.c.v. injection of Aβ(23-35) can significantly suppress the HFS-induced LTP in the CA1 area of rat hippocampus in vivo, implying that the Aβ deposited in the brain of patients with Alzheimer's disease may impair the function of learning and memory by suppressing the hippocampal LTP. The facts that the extent of inhibition of Aβ(23-35) and genistein on LTP was similar and no further potentiation of the suppression was observed when Aβ(23-35) and genistein were co-applied suggest that PTK is probably involved in the Aβ-induced suppression of hippocampal LTP.

Involvement of nicotinic acetylcholine receptors in amyloid β-fragment-induced intracellular Ca(2+) elevation in cultured rat cortical neurons / 生理学报

The amyloid β-protein (Aβ)-induced disturbance of intracellular calcium homeostasis has been regarded as the final route whereby Aβ insults neurons. However, the mechanism of Aβ-induced Ca(2+) overloading is still unclear so far. Especially, it remains to be clarified whether nicotinic acetylcholine receptors (nAChRs) are involved in the Aβ-induced elevation of intracellular calcium concentration ([Ca(2+)](i)). In the present study, we observed the effects of Aβ fragments 25-35 (Aβ(25-35)) and 31-35 (Aβ(31-35)) on [Ca(2+)](i) in primary cultured rat cortical neurons using laser-scanning confocal calcium imaging technique, and investigated its probable cholinergic mechanism. The results showed that: (1) Both Aβ(25-35) and Aβ(31-35) induced similar and significant [Ca(2+)](i) elevation in a concentration-dependent manner, and no statistical difference was found between the effects of both peptides; (2) The reverse peptide of Aβ(31-35), i.e. Aβ(35-31), had no effect on [Ca(2+)](i) elevation; (3) Mecamylamine (MCA), a non-specific nAChRs antagonist, significantly and dose-dependently blocked the [Ca(2+)](i) elevation induced by Aβ(25-35) or Aβ(31-35) (4) Dihydro-β-erythroidine (D-β-E), a specific α4β2 subtype nAChRs antagonist, also significantly inhibited the [Ca(2+)](i) elevation induced by Aβ(25-35) and Aβ(31-35), but the effect was weaker than the effect of MCA at the same concentration. These results indicate that Aβ(31-35) may be a shorter active sequence in full length of Aβ molecule, and the overactivation of nAChRs, including α4β2 subtype, may be, at least partly, responsible for the Aβ-induced elevation of [Ca(2+)](i) in cultured rat cortical neurons. Thus, the present study suggests a new potential target of Aβ in the brain, and provides a new insight into the mechanisms by which Aβ impairs the cognitive function in Alzheimer's disease.

Determination of icaritin in rat plasma by HPLC-MS/MS / 药学学报

The paper is to report the development of a high-performance liquid chromatographic/tandem mass spectrometry (HPLC-MS/MS) method for the determination of icaritin (ICT) in rat plasma. After precipitated with acetonitrile from the plasma, ICT was isolated chromatographically on a Dikma C18 column. The mobile phase consisted of acetonitrile-water-acetic acid (72 : 28 : 1.5, v/v/v). Electrospray ionization (ESI) source was applied and operated in the positive ion mode. Multiple reaction monitoring (MRM) mode with the transitions of m/z 387 --> m/z 313 and m/z 331 --> m/z 315 were used to quantify ICT and the internal standard, respectively. The linear calibration curve was obtained in the concentration range of 2.5-1,000 ng x mL(-1). The lower limit of quantification was 2.5 ng x mL(-1). The inter- and intra-day precision (RSD) were less than 9.63%, and the accuracy (relative error) was within +/-7.42%. The method was proved to be suitable for the pharmacokinetics of ICT, which offers advantages of high sensitivity and selectivity.

Clinical characteristics of and related treatments on 1004 patients with acute myocardial infarction from March 2004 to March 2007 / 中华流行病学杂志

Objective To study the change of baseline clinical characteristics including prehospital delayed time(PDT),modes of transportation and treatment for patients with acute myocardial infarction (AMI)in the past 3 years.Methods We used the same questionnaire to accurately collect and retrospectively analyze the data regarding clinical characteristics of all 1004 patients with AMI,who consecutively presented to the Emergency Unit and Emergency Intensive Care Unit(EICU)of Beijing Anzhen Hospital from March 12th 2004 to March 11th 2007.According to the time of onset of the disease,all patients were divided into 3 groups:group A(from Mar.12th 2004 tO Mar.11th 2005),group B(Mar.12th 2005 to Mar 11th 2006)and group C(Mar.12th 2006 to Mar.11th 2007).Clinieal characteristics and treatment were compared.Results There were significant differences in the number of patients with histories of stroke,coronary artery disease or smoking among the three groups(P＜0.05).No obvious differences in the median of PDT were found among the three groups(P＞0.05).More patients accepted reperfusive therapy in group C compared to group A(P＜0.05),although the mortality rates of AMI among these 3 years were similar.Conclusion Though more people started to have accepted reperfusion therapy,mortality failed to show an obvious decrease.Subject as how tO shorten the PDT called for further study.

Berberine ameliorates renal injury in streptozotocin-induced diabetic rats by suppression of both oxidative stress and aldose reductase / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Berberine is one of the main constituents of Coptidis rhizoma (CR) and Cortex phellodendri. In this study, we investigated the beneficial effects of berberine on renal function and its possible mechanisms in rats with diabetic nephropathy (DN).</p><p><b>METHODS</b>Male Wistar rats were divided into three groups: normal, diabetic model, and berberine treatment groups. Rats in the diabetic model and berberine treatment groups were induced to diabetes by intraperitonal injection with streptozotocin (STZ). Glomerular area, glomerular volume, fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (Cr) and urine protein for 24 hours (UP24h) were measured using commercially available kits. Meanwhile, the activity of superoxide dismutase (SOD), content of malondialdehyde (MDA) in serum, activity of aldose reductase (AR) and the expression of AR mRNA and protein in kidney were detected by different methods.</p><p><b>RESULTS</b>The results showed that oral administration of berberine (200 mg x kg(-1) x d(-1)) significantly ameliorated the ratio of kidney weight to body weight. Glomerular area, glomerular volume, FBG, BUN, Cr and UP24h were significantly decreased in the berberine treatment group compared with the diabetic model group (P < 0.05). Berberine treatment significantly increased serum SOD activity and decreased the content of MDA compared with diabetic model group (P < 0.05). AR activity as well as the expression of AR mRNA and protein in the kidney was markedly decreased in the berberine treatment group compared with diabetic model group (P < 0.05).</p><p><b>CONCLUSION</b>These results suggested that berberine could ameliorate renal dysfunction in DN rats through controlling blood glucose, reduction of oxidative stress and inhibition of the activation of the polyol pathway.</p>

Upregulated voltage-gated potassium channel Kv1.3 on the CD4+CD28null T lymphocyte from patients with acute coronary syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>The purpose of our study is to observe the voltage-gated potassium channel Kv1.3 expression on CD4+CD28null T cells from the peripheral blood of ACS patients by the patch clamp technique.</p><p><b>METHODS</b>Kv1.3 potassium channels expression from 17 patients with ACS and 11 healthy age-matched normal controls was detected in single cell (CD4+CD28null T cells and CD4+CD28+ T cells) by fluorescence microscopy and patch clamp.</p><p><b>RESULTS</b>The percent of CD4+CD28nullT cells are higher in the ACS (6.97% +/- 2.05%) than that in the controls (1.38% +/- 0.84%, P < 0.05). The concentration of hsCRP is directly correlated with the number of the CD4+CD28null T cells in the ACS (r = 0.52, P < 0.05). The conductance [(6.89 +/- 1.17) nS vs. (3.36 +/- 0.66) nS], dens [(1.95 +/- 0.80) n/microm2 vs. (1.13 +/- 0.57) n/microm2] and numbers [(574.5 +/- 97.6) n/cell vs. (280.3 +/- 55.3) n/cell] of the Kv1.3 channels on the CD4+CD28null T cells are significantly higher than those on the CD4+CD28+ T cells (all P < 0.01) in ACS patients, but were similar on CD4+CD28+ T cells between ACS patients and controls.</p><p><b>CONCLUSION</b>The CD4+CD28null T cells in the ACS and the numbers of Kv1.3 channels on the CD4+CD28null T cells from the ACS patients are significantly upregulated and might contribute to the pathogenesis of ACS.</p>