Screening small molecular inhibitors of STAT3 based on surface plasmon resonance technology / 药学实践杂志

Objective To find small molecules binding specifically to signal transducer and activator of transcription3 (STAT3) based on surface plasmon resonance (SPR) technology and confirm their inhibitory activities to STAT3. Methods The biomolecular interaction analysis T200 system based on SPR technology was used to couple the purified protein STAT3 to CM5 chip under the optimal pH conditions. The compounds with high binding response value were screened out from 50 candidate compounds derived from traditional Chinese medicines and the binding specificity was then confirmed. Biological experiments were performed to confirm the inhibitory effects of the screened compounds on STAT3. The binding pattern of STAT3 and the compound was fitted by molecular docking technique. Results More than 10 candidate molecules exhibited binding activities to STAT3 and kinetics assays revealed that only one candidate molecule, apigenin, showed specific binding. Western-blot analysis exhibited that apigenin inhibited the phosphorylation of STAT3 dose-dependently. Luciferase reporter gene assays demonstrated that apigenin also inhibited IL-6-induced STAT3 transcriptional activity in a dose-dependent manner. Molecular docking results showed that apigenin binds to the SH2 domain of STAT3, and interacts with key residues Glu638, Gln644, Gly656 and Lys658 by hydrogen bonds and with Tyr657 through π-π interactions. Conclusion Apigenin was a direct inhibitor of STAT3.

Analysis of 644 Children's Misusage Medicine Characteristics / 中国药房

OBJECTIVE:To reduce children's mistaking medicine and improve the safety of drug use in children.METHODS:Case number of children's mistaking medicine,the number of poisoning,age distribution and types of mistaken medicine in hospital information system of Beijing Children's Hospital of Capital Medical University during 2014-2016 were counted to analyze data characteristics and put forward relevant preventive strategies.RESULTS & CONCLUSIONS:In 3 years,there were 644 cases of children's mistaking medicine,accounting for 30％ of total number of children poisoning (2 100 cases).A high-risk group concentrated in the 1-4 years old children.The types of mistaking medicine were mostly antihypertensive drugs,antipyretic and analgesic drugs,sedative drugs and antiepileptic drugs.Top 3 medicines were clonazepam (29 cases),ibuprofen (28 cases),aeetaminophen and its compound (12 cases).The main causes of mistaking medicine are mainly associated with hyperactivity,curiosity,imitation and other behavioral characteristics,high availability of drug storage,etc.Types of mistaken medicine are commonly used drugs for the elderly in the family and antipyretic analgesics commonly used in children.It is suggested to prevent the occurrence of children's mistaking medicine from aspects of child nursing person,government and medical institutions by reducing the children accessibility of drugs stored at home,designing drug package difficult to open for children,improving medication compliance of child nursing person,etc.

Preparation and performance properties of functionalized multi-walled carbon nanotubes/chitosan-zinc composite scaffolds / 中国组织工程研究

BACKGROUND:A pure chitosan (CS) scaffold has poor mechanical properties,and cannot play a load-bearing role in the bone defect region.Therefore,many scholars attempt to develop multi-walled carbon nanotube (MWCNT)/chitosan (MWCNT/CS) bone tissue scaffolds.OBJECTIVE:To develop the functionalized MWCNT/CS composite scaffolds carrying zinc (f-MWCNT/CS-Zn) and to test its mechanical properties,antibacterial activity and biocompatibility.METHODS:(1) F-MWCNT composite scaffolds were prepared by the acid mixture method,and f-MWCNT/CS-Zn composite scaffolds were prepared through mixing CS,f-MWCNT (0.5％) with different concentrations of ZnSO4·7H2O (the concentrations of Zn in the composite scaffolds were 0.2％,1％,2％,respectively).The surface hardness and tensile strength of the pure CS scaffold and the f-MWCNT/CS-Zn composite scaffolds were measured.(2) The inhibitory effect on Staphylococcus aureus or Escherichia coii of the pure CS scaffold and f-MWCNT/CS-Zn scaffolds was tested by inhibition zone test.(3) The osteoblasts MC3T3-El were cultured with the leaching solution of f-MWCNT/CS-Zn composite scaffolds.The cell proliferation was detected by MTT assay at 1,2,3 days after culture,then the relative proliferation rate was calculated and the cytotoxicity was evaluated.RESULTS AND CONCLUSION:(1) The surface hardness and tensile strength of the f-MWCNT/CS-Zn composite scaffolds were higher than those of the pure CS scaffold (P ＜ 0.05),and there was no significant difference in the surface hardness and tensile strength between the different zinc-containing composite scaffolds.(2) The antibacterial properties of the three f-MWCNT/CS-Zn composite scaffolds against Staphylococcus aureus and Escherichia coii were higher than those of the pure CS scaffold (P ＜ 0.05),and the antibacterial activity was enhanced with the increase of zinc mass fraction.(3) The f-MWCNT/CS-0.2％Zn and f-MWCNT/CS-1％Zn composite scaffolds had no cytotoxicity.To conclude,the f-MWCNT/CS-1％Zn composite scaffold has good mechanical properties,antibacterial activity and biocompatibility.

Predictors to assess non-sentinel lymph node status in breast cancer patients with only one sentinel lymph node metastasis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The purpose of this study was to investigate the feasibility of avoiding axillary lymph node dissection (ALND) for patients with only one sentinel lymph node (SLN) metastasis. The characteristics and predictive factors for non-sentinel lymph node (NSLN) metastasis of patients with single positive SLN were also analyzed.</p><p><b>METHODS</b>Patients with no and only one SLN metastasis (0/n and 1/n group, n ≥ 2) were selected from 1228 cases of invasive breast carcinoma, who underwent axillary dissection in Shandong Cancer Hospital between November 1999 and December 2011, to compare the characteristics of NSLN metastasis between them. For the 1/n group, the factors that influenced the NSLN metastasis were analyzed by univariate and multivariate analysis.</p><p><b>RESULTS</b>Differences of the NSLN metastasis between the 0/n and the 1/n groups were significant (P < 0.001). There was no significant difference between the axillary lymph node metastasis on level III in 1/n group and 0/n group (P = 0.570). When the total SLN number was ≥ 4 and with one positive case, the NSLN metastasis was not significantly different from that in the 0/n group (P = 0.118). In the 1/n group, clinical tumor size (P = 0.012), over-expression of Her-2 (P = 0.003), tumor grade (P = 0.018) and the total number of SLN (P = 0.047) significantly correlated with non-SLN metastasis. Clinical tumor size (P = 0.015) and the expression of Her-2 (P = 0.01) were independent predictive factors for non-SLN metastasis by the Logistic regression model.</p><p><b>CONCLUSION</b>Under certain conditions, breast cancer patients with single SLN metastasis could avoid ALND.</p>

Analysis of clinicopathological factors associated with false-negative rate of sentinel lymph node biopsy in breast cancer patients: experience of a single center / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The purpose of this study was to investigate the clinicopathologic factors associated with false-negative rate of sentinel lymph node biopsy (SLNB) in breast cancer, and to explore how to reduce the false-negative rate of SLNB.</p><p><b>METHODS</b>The clinicopathological data of 2265 patients with invasive breast carcinoma who underwent sentinel lymph nodes biopsy (SLNB) in Shandong Cancer Hospital between November 1999 and December 2011 were retrospectively analyzed. We screened 1228 patients who received axillary lymph node dissection after SLNB, and studied the clinicopathological factors that could be associated with false-negative rate of SLNB.</p><p><b>RESULTS</b>The false negative rate of this group was 10.7% (73/683), accuracy rate was 94.1% (1155/1228), and negative predictive value was 88.2% (545/618). Clinical tumor size (all P < 0.05), calendar year of surgery (all P < 0.05) and numbers of detected SLNs (all P < 0.05) were significantly related with false negative rate and accuracy rate of SLNB, determined by single factor analysis. Logistic regression model analysis showed that calendar year of surgery (P = 0.034) and numbers of detected SLNs (P = 0.012) were independent predictive factors for the false negative rate of SLNB.</p><p><b>CONCLUSIONS</b>False negative rate and accuracy rate of SLNB are significantly related to the calendar year of surgery and number of detected SLNs. Strict case selection, standard operation procedure, increaseing numbers of detected SLNs, and improvement of the skill of operators are effective measures to reduce the false negative rate of SLNB.</p>

Effects of substrate stiffness on the migration of hepatic and hepatoma carcinoma cells / 医用生物力学

Objective To investigate the cause of tumor cell migration by comparing the effect of substrate stiffness on hepatic and hepatoma carcinoma cell migration so as to understand the invasive characteristics of tumor cells. Methods Immunofluorescence staining, morphological analysis and transwell were employed to observe the morphological characteristics of HCCLM3 and L02 cells on different substrates and test their migration characteristics with the quantitative analysis. Results (1) The migration rate and net translocation of HCCLM3 and L02 cells on 4 kPa substrate was higher than those both on 0.5 kPa(most soft one) and on glass (the hardest one) substrates, and L02 cells also displayed higher migration efficiency than HCCLM3 cells on such substrates. (2) The mean squared displacement of HCCLM3 and L02 cells on different substrates showed consistent tendency, and the directional persistence of L02 cells on the softer substrate was significantly higher than that of HCCLM3 cells. (3) In 0.5 and 1 mg/mL three dimensional collagen environment, the number of invasive cells of HCCLM3 was remarkably more than that of L02 cells. After adding MMPs inhibitor GM6001 (40 μg/mL), the number of invasive cells was notably increased in HCCLM3 cells, but notably decreased in L02 cells. Conclusions (1) In two dimensional comparatively soft environment, L02 cells displayed an efficient migration due to its higher directional persistence. (2) In three-dimensional collagen environment, the invasion efficiency of HCCLM3 cells was significantly higher due to the various modes of migration adaptation to the microenvironment.

Analysis on the Situation of Abundant Drugs vs. Few Categories Involved in Essential Drug List in China / 中国药房

OBJECTIVE:To promote the adjustment of National Essential Drug List and implementation of Essential Drug List. METHODS:National Essential Drug List was compared with Essential Drug List issued by WHO. Retrieved from statistical results conducted by State Food and Drug Administration, the problem that there were large number of drug in China while little category were included in National Essential Drug List was analyzed, according to practice in China. RESULTS & CONCLUSION: Drug enterprises increased the dosage form and category of preparation blindly because of huge raw drug market, various dosage forms and weak administration to drug enterprises. The characteristics of drug were cheap, high quality, acceptance by state, which decided that the category of drug in Essential Drug List should not be too much. It is necessary to adjust Essential Drug List as the change of situation so as to meet the requirement of public health.

Coexistence of the Problem Between Medical Insurance List and Essential Drugs List / 中国药房

OBJECTIVE: To explore the coexistence of "Medical Insurance List" and "Essential Drugs List". METHODS: A comparative similarities and differences analysis of the scope, role, to develop the basis for the implementation of the effectiveness between the "medical insurance directory" and "Essential Drugs List" was carried out. RESULTS & CONCLUSION: The new edition of "Essential Drugs List" is to ease the contradiction of coexistence in long-term, but they are difficult to reconcile in short-term.

Investigation on the Issues about Distribution of National Essential Drug / 中国药房

OBJECTIVE:To explore the issues about distribution of national essential drug system to promote the implementation of national essential drug.METHODS:The problems in the distribution of essential drug and Japan's advanced experience were analyzed in order to put forward suggestion for distribution of essential drug.RESULTS & CONCLUSION:The problems in the distribution of essential drug mainly contained low earnings,shortage of business impetus,ambiguous evaluation criteria and irrational distribution of circulation enterprise.The distribution of essential drug should be supervised strictly by absorbing the experience of Japanese pharmaceutical logistic.Rural Two Network should be improved and the logistics capabilities of pharmaceutical enterprises should be strengthened.JIT purchase mode of essential drug should be established in medical institutions as well as third party logistics.

Effect and safety of losartan and captopril for the treatment of essential hypertension: A systematic review / 解放军医学杂志

Objective To assess the efficacy and safety of losartan and captopril for the treatment of essential hypertension.Methods The database was retrieved form China Journal Full-text Database(1994-2008.10),Chinese Biomedicine Database(1978-2008.10),Chinese Scientific Journals Full-text Database(1989-2008.10),WanFang database online(1982-2008.10),PubMed(1966-2008.10),Cochrane Library(Issue 4,2008),EMBASE(1900-2008.10),and SCI(1974-2008.10).Randomized control trials(RCTs) of losartan and captopril for essential hypertension were included.The methodological quality of included studies was assessed independently by two authors.The quality of the included studies was evaluated by Handbook 4.2.6 recommend standard.Data were analyzed by RevMan 4.2.10 from the Cochrane Collaboration.Results Eleven RCTs(including 1458 patients) met the inclusion criteria.① Treatment for 4 weeks: There was a significant lowering of clinic systolic blood pressure(SBP) in losartan group compared with that in captopril group [WMD=0.59,95%CI(0.22~0.55),P=0.002];while no statistically significant difference existed between the two groups in clinic diastolic blood pressure(DBP) [WMD=-0.08,95%CI(-1.11~0.94),P=0.87].② Treatment for 8 weeks: no significant difference was found between losartan group and captopril group in the lowering of clinic SBP [WMD=0.26,95%CI(-0.08~0.61),P=0.14] and DBP [WMD=0.13,95%CI(-0.28~0.54),P=0.54].③ Treatment for 12 weeks: no statistically significant difference existed between the two groups in clinic SBP [WMD=1.75,95%CI(-0.22~3.72),P=0.08] and DBP [WMD=1.15,95%CI(-2.81~5.11),P=0.57].④ The side effect in losartan group was lower than that in captopril group [OR=0.55,95%CI(0.42~0.73),P=0.00].Conclusions Based on the review,losartan is more effective and safe in lowering SBP compared with captopril.Further high-quality randomized controlled trials are needed to provide reliable evidence on the treatment of patients with essential hypertension.