Bioinformatics analysis on differential expression genes of neutrophilic asthma and drug screening / 中国药理学通报

Aim To explore the differential expression genes (DEGs) and potential therapeutic drugs of neutrophilic asthma (NA) based on bioinformatics analysis and molecular docking. Methods The gene expression profiles of NA were obtained from GEO database, and the differential expression genes were screened. The protein-protein interactions (PPI) of DEGs were obtained from STRING database, and the hub genes were screened by Cytoscape according to the degree of DEGs. The GO and KEGG pathway analysis were performed by DAVID database. Finally, molecular docking technology was used to screen the potential therapeutic drugs for the treatment of NA. Results A total of 147 DEGs were obtained from NA patients compared with healthy people in GEO database. Ten hub genes were screened from PPI network, including CXCL8, FPR2, CXCL1, TNFRSF1B, CXCR1, etc. Go enrichment analysis showed that DEGs were mostly associated with inflammation, immune response and chemotaxis, etc. KEGG pathway analysis indicated that the DEGs were mainly involved in cytokine-cytokine receptor interaction and complement and coagulation signaling pathways. Molecular docking showed that paeoniflorigenone and triptolide had good binding activity with C8B and PLAU. Conclusion Complement and coagulation cascades may become a new therapeutic target of NA. The two screened compounds paeoniflorigenone and triptolide may be potential therapeutic drugs for the treatment of NA.

Prognostic value and initial exploratory research on TNM staging method of tumor deposits in stage III colon cancer / 中华胃肠外科杂志

Objective@#To investigate the effect of tumor deposits (TD) on the prognosis of patients with stage III colon cancer, and to explore whether TD number included into regional lymph node count can predict the prognosis more accurately.@*Methods@#A retrospective cohort study was carried out. Case inclusion criteria: (1) primary colon cancer; (2) undergoing colon cancer radical operation; (3) definite pathological diagnosis; (4) colon cancer stage III according to AJCC 8th edition; (5) complete follow-up data; (6) without preoperative neoadjuvant treatment. Clinicopathological data of 296 patients undergoing colon cancer radical operation from January 2005 to December 2008 in the Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively collected. The effect of TD and its amount on the prognosis was evaluated. Colon cancer TNM staging method based on the 8th edition of AJCC was compared with the modified TNM staging (mTNM) adjusted by the number of TD. The differences of the disease-free survival (DFS) and overall survival (OS) between groups were also examined. The Kaplan-Meier curve was used to analyze the survival, and prognostic factors were analyzed by Cox univariate and multivariate analyses.@*Results@#Among 296 patients with stage III colon cancer, 78 patients had TD. The median number of TD was 2 (1-10). Tumor T stage, N stage, vascular tumor thrombus and preoperative carcinoembryonic antigen (CEA) were associated with TD in patients with colon cancer (all P<0.05). The right hemicolon appears likely to have TD than left hemicolon, but the difference was not statistically significant (P=0.059). The median follow-up of the whole group was 71 (6-102) months. During the follow-up period, 129 patients (43.6%) had recurrence or metastasis, and 111 patients died (37.5%). The 5-year DFS in TD group was 44.9%, which was lower than that in the non-TD group (60.6%), with statistically significant difference (P=0.003). The 5-year OS in TD group was 50.0%, which was also lower than 67.0% in the non-TD group, and the difference was statistically significant (P=0.002). According to TD number, patients were divided into 3 groups: 1 TD (25 cases), 2-3 TD (32 cases), ≥4 TD (21 cases). The 5-year DFS in these 3 groups was 68%, 56.3%, and 0, respectively (P<0.001), and 5-year OS was 76%, 59.4%, and 4.8% respectively (P<0.001). Univariate analysis showed that TD presence (95% CI: 1.234-2.694, P=0.003) and TD number (95% CI: 3.531-14.138, P<0.001) were associated with the prognosis of patients with stage III colon cancer. At the same time, age, tumor N stage, tumor location, chemotherapy, and preoperative CEA elevation were also associated with the prognosis of stage III colon cancer patients (all P<0.05). Multivariate analysis revealed that TD presence (HR=1.957, 95%CI: 1.269-3.017, P=0.002) and TD number (HR=8.020, 95% CI: 3.414-18.842, P<0.001) were still independent risk factors for the prognosis of patients with stage III colon cancer.According to the TD number counted as metastatic lymph nodes, in 78 patients with TD, 24 patients were upstaged in N stage, and 16 patients upstaged from TNM stage IIIB to stage IIIC. For 16 stage IIIB cases with staging modification, 30 unadjusted stage IIIB cases with TD, and 148 stage IIIB cases without TD, the 5-year OS was 37.5%, 73.3% and 76.4%, respectively with significant difference (P<0.001). However, for 16 patients adjusted as stage IIIC (mTNM), 32 patients with unchanged stage IIIC with TD (TNM, AJCC 8th edition), and 63 stage IIIC cases without TD, the 5-year OS was 37.5%, 36.4%, and 41.3%, respectively without significant difference (P=0.707).@*Conclusions@#TD presence and TD number are independent risk factors for prognosis of stage III colon cancerpatients. TNM staging evaluation with lymph node number including TD number can predict the prognosis of patients more accurately.

Study on Practice and Effect of SIMPLE Pharmaceutical Care Mode in Chronic Disease Management of Bronchial Asthma and COPD Patients / 中国药房

OBJECTIVE:To adopt SIMPLE pharmaceutical care mode in chronic disease management of bronchial asthma and COPD patients,and to evaluateits the effect. METHODS:By random sampling,a total of 200 bronchial asthma and COPD patientsselected from respiration department in the First Affiliated Hospital of Soochow University during Sept. 2016-Jun. 2017 were divided into control group(100 cases)and intervention group(100 cases)by simple randomization. Control group received routine treatment. Intervention group additionally received education on quitting smoking,effective use of the inhaler,monitoring detection indexes, selecting drugs correctly,scientific life style. Inhaled device scores,lung function indexes (FEV1％,FEV1/FVC),the number of patients with acute attack/exacerbation,clinical effective control rates,ADR occurrence rates,compliance of using apparatus(MMAS-8 score)were compared between 2 groups before enrollment,3 and 6 months after enrollment. RESULTS:Commpared with during enrollment,inhaled device score,clinical effective control rate and MMAS-8 score of intervention group incereased significantly 3,6 months after enrollment,while patients with acute attack/exacerbation ≥2 times decreased significantly,with statistical significance (P<0.05). Compared with control group,inhaled device score,clinical effective control rate,MMAS-8 score and FEV1％ of intervention group increased significantly,patients with acute attack/exacerbation ≥2 times decreased significantly 3 and 6 months after enrollment with statistical significance (P<0.05);the ADR occurrence rate was lower than control group,with statistical significance (P<0.05). CONCLUSIONS:Chronic disease management of bronchial asthma and COPD patients with SIMPLE pharmaceutical care mode can improve medication compliance and clinical efficacy,and reduce ADR.

Therapeutic effect of clopidogrel combined aspirin on acute myocardial infarction / 心血管康复医学杂志

Objective :To comprehensively analyze therapeutic effect of clopidogrel combined aspirin on acute myo-cardial infarction (AMI).Methods :A total of 100 AMI patients treated in our hospital were selected ,and equally divided into clopidogrel group and combined treatment group (received clopidogrel combined aspirin ).Both groups received routine treatment for 4 weeks .Total effective rate ,platelet aggregation rate (PAR) ,coronary recanaliza-tion time ,prothrombin time (PT) ,left ventricular ejection fraction (LVEF) and incidence rate of cardiovascular e-vents during hospitalization were compared between two groups .Results :Total effective rate of combined treatment group was significantly higher than that of clopidogrel group (96. 00% vs.80.00%, P＝0.014).Compared with clopidogrel group after treatment ,there were significant reductions in PAR [ (47.63 ± 7.83)% vs.(38.45 ± 8.55)%] ,incidence rate of cardiovascular events (24.00% vs.4.00%) and coronary recanalization time [(45.44 ± 4.42) vs.(41.93 ± 5.85)] ,P and significant rise in LVEF [ (48.56 ± 5.79)% vs.(55.51 ± 6.44)%] in combined treatment group , P＜0. 01 all.Conclusion : The clinical effect of clopidogrel combined with aspirin in the treatment of acute myocardial infarction is significant .

Clinical Evaluation and Implement of Grading Pharmaceutical Care on Patients with Asthma and COPD / 中国药学杂志

OBJECTIVE: To discuss the mode of grading pharmaceutical care on patients with asthma and chronic obstructive pulmonary disease (COPD). METHODS: Combined with guidelines on patients with asthma and COPD,, the standards for grading pharmaceutical services were formulated. Two hundred and fifth-six patients are divided into intervention group and control group. And patients were given different levels of pharmaceutical services with grading standard. Before the intervention, 3 months and 6 months after intervention, grading score, medication compliance and lung function index (FEV1/FVC, FEV1% value) were expected to make the comparison between the two groups. The incidence of adverse reactions, the number of exacerbations greater than or equal to 2 times and clinical control rate were observed. RESULTS: Compared with control group, 6 months after intervention, the proportion of first intervention decreased by 25%, the incidence of adverse reactions decreased by 7.82%, the number of exacerbations greater than or equal to 2 times was reduced by 7.81%, the rate of clinical effective increased by 23.43%, FEV1/FVC, FEV1% value and medication adherence has improved significantly (P<0.05). CONCLUSION: The grading pharmaceutical care for patients with asthma and COPD, can help pharmacists find the crucial guardianship objects in the shortest time, and improve the quality of pharmaceutical care and clinical effect.

Application of QCC in Improving the Compliance of Asthma/COPD Outpatients Handling Inhaler Devices / 中国药房

OBJECTIVE:To evaluate the effects of quality control circle(QCC)in improving the compliance of asthma/COPD outpatients handling inhaler devices. METHODS:By simple random sampling method,90 asthma/COPD outpatients receiving Tiotropium bromide powder for inhalantion,Salmeterol xinafoate and fluticasone propionate powder for inhalantion and Budesonide and formoterol fumarate powder for inhalantion were selected from our hospital during Apr. to Nov. 2015. The reasons for poor com-pliance of handling inhaler devices were analyzed by QCC. The countermeasures were formulated to improve the compliance,in-cluding clinical pharmacist education,follow-up,issuing education manuals,developing WeChat consulting. Operation step score of inhaler devices,compliance score and activity ability score of QCC members were analyzed statistically before and after QCC. RESULTS:After the development of QCC,operation step score of inhaler devices and compliance score in 90 asthma/COPD outpa-tients increased from 7.7 and 7.7 before activity to 8.8 and 9.3 after activity,the achievable rate of compliance was 114.3%,and the improvement rate was 20.8%. The sense of honor,responsibility,self-confidence,QCC techniques,communication and coordi-nation,team cohesion of all members were all improved obviously. CONCLUSIONS:QCC activity improves the compliance of asthma/COPD outpatients handling inhaler devices and shows the professional service level of clinical pharmacists,which is of sig-nificance to the improvement of pharmaceutical care.

Evaluation and analysis of inhaler drug device adherence in asthma and COPD patients / 中国药学杂志

OBJECTIVE: To investigate the factors influencing the adherence of asthma and chronic obstructive pulmonary disease (COPD) patients with inhaler drug device, and improve patients adherence. METHODS: One hundred patients were collected and randomly divided into intervention group and control group. By seven steps form England in combination with the usage of Chinese patients with inhaler drug device, the suction operation was into ten steps and the reasons of the poor adherence were analyzed. Observed two groups of devices adherence, adverse reactions, the number of exacerbations greater than or equal to 2 times. RESULTS: Compared with control group, 6 months after evaluation, the devices adherence of intervention group increased by 24.82%-35.09%. Incidence of adverse reactions decreased by 8.00%. The number of exacerbations greater than or equal to 2 times was reduced by 12.00%. CONCLUSION: The adherence of inhaler drug device is associated with incidence of adverse reactions and the number of exacerbations. The pharmacists can improve patients adherence by intervene the operation of device. And the device adherece brought into the assessment of medication adherence is necessary.

Analysis of the relationship of DNA mismatch repair with clinicopathologic features and prognosis of colon cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the relationship between DNA mismatch repair (MMR) and clinicopathologic features and prognosis in patients with stages II and III colon cancers.</p><p><b>METHODS</b>The clinical and pathological data of 440 patients with stage II/III colon cancer after radical resection were retrospectively reviewed and analyzed. Immunohistochemical staining was used to assess the expression of MMR proteins (MLH1, MSH2, MSH6 and PMS2), and the correlation between DNA MMR and clinicopathological features and prognosis of colon cancers was analyzed.</p><p><b>RESULTS</b>Of the 440 tumor samples tested for DNA mismatch repair status, 90 (20.5%) demonstrated defective DNA mismatch repair and 350 (79.5%) had proficient DNA mismatch repair. Defective DNA mismatch repair (dMMR) was associated with young patients (≤ 60), proximal colon cancer, stage II, poorly differentiated adenocarcinoma and mucinous adenocarcinoma (P<0.05 for all). Among the 440 patients, 126 (28.6%) cases had recurrence or metastasis and 93 (21.1%) died during the median follow-up of 61.0 months. The five-year disease-free survival (DFS) rate was 82.2% among the patients with tumor exhibiting dMMR, significantly higher than that in patients with tumors exhibiting pMMR (68.9%, P=0.02). The univariate and mutlivariate analyses showed that the MMR status is an independent factor affecting 5-year disease-free survival and overall survival (OS) in colon cancer patients (P<0.05 for both).</p><p><b>CONCLUSIONS</b>Defective DNA mismatch repair (dMMR) is associated with patients with proximal colon cancer, stage II and poorly defferentiated adenocarcinoma and mucinous adenocarcinoma. The prognosis for patients with dMMR is better than those with pMMR. dMMR may be a useful biomarker for the prognosis of colon cancer.</p>

Correlations between DNA mismatch repair (MMR) and prognosis and prediction of treatment efficacy in stage II/II colon cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the role of DNA mismatch repair (MMR) as a prognostic indicator of radical resection and a predictor of fluorouracil-based adjuvant therapy benefit in patients with stage II/III colon cancer.</p><p><b>METHODS</b>The clinicopathological characteristics of 172 patients with stage II/III colon cancer who underwent radical resection were retrospectively analyzed. Immunohistochemical staining was used to detect the expression of DNA mismatch repair (MLH1/MSH2/MSH6/PMS2) in the tumor tissues.</p><p><b>RESULTS</b>Among a total of 172 patients, there were 38 (22.1%) cases with defective DNA mismatch repair (dMMR) and 134 (77.9%) cases with proficient DNA mismatch repair (pMMR). Among the 115 patients who did not receive adjuvant chemotherapy, those with tumor displaying dMMR had a better 5-year overall survival (OS) rate and disease-free survival (DFS) rate than the patients with proficient DNA mismatch repair (pMMR) (88.0% vs. 66.7%, P = 0.040; 84.0% vs. 60.0%, P = 0.034). The benefit of adjuvant chemotherapy differed significantly according to the MMR status. Adjuvant 5-Fu chemotherapy improved the 5-year overall survival rate among 134 patients with pMMR (86.4%) than that in patients treated by surgery alone (66.7%, P = 0.012). By contrast, there was no benefit of adjuvant 5-Fu chemotherapy in the patients with dMMR (61.5% vs. 86.4%, P = 0.062), which was even more clear the 5-year disease-free survival rate (53.8% vs. 84.0%, P = 0.038).</p><p><b>CONCLUSIONS</b>MMR status is a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II/III colon cancer. Patients with stage II/III colon cancer displaying dMMR have a better prognosis than those with pMMR.</p>

Famitinib in metastatic renal cell carcinoma: a single center study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Famitinib is a novel and potent multitargeting receptor tyrosine kinase inhibitor. The phase I clinical study showed that famitinib was well tolerated and had a broad anti-tumor spectrum. The purpose of this study was to examine the efficacy and safety of famitinib for the treatment of metastatic renal cell carcinoma (mRCC).</p><p><b>METHODS</b>The data of famitinib in treating patients with mRCC from the single-center phases I and II clinical trials were analyzed. Famitinib was administered orally at the dose of 13-30 mg once daily until tumor progression, occurrence of intolerable adverse reactions or withdrawal of the informed consent.</p><p><b>RESULTS</b>A total of 24 patients with mRCC were treated including 17 patients at a dose of 25 mg once daily, 4 patients at a dose of 27 mg and 1 patient each at a dose of 13 mg, 20 mg and 30 mg, respectively. Twelve (50.0%) patients achieved partial response (PR) and 9 patients achieved stable disease (SD). Progressive disease was found in 3 (12.5%) patients. The disease control rate was 87.5%. The median follow-up time was 17.6 months; the median progression free survival (PFS) was 10.7 (95% CI 7.0-14.4) months; and the estimated median overall survival (OS) time was 33.0 (95% CI 8.7-57.3) months. The adverse drug reactions mainly included hypertension (54.1%), hand-foot skin reactions (45.8%), diarrhea (33.3%), mucositis (29.2%), neutropenia (45.8%), thrombocytopenia (29.2%), hyperlipidemia (41.7%) and proteinuria (41.7%). The incidence rate of grades 3 and 4 adverse events was low, mainly including hypertension 12.5%, hand-foot skin reactions 4.2%, neutropenia 4.2%, thrombocytopenia 4.2%, hyperlipidemia 4.2% and proteinuria 12.5%.</p><p><b>CONCLUSIONS</b>Famitinib has significant anti-tumor activity in mRCC. The common adverse reactions are generally manageable.</p>

A phase II trial of oxaliplatin plus S-1 as a first-line chemotherapy for patients with advanced gastric cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Palliative chemotherapy has been shown to have a survival benefit for patients with recurrent or metastatic gastric cancer. We conducted a Phase II trial to determine the efficacy and safety of S-1 plus oxaliplatin (SOX regimen) as first-line chemotherapy for patients with unresectable locally advanced or metastatic gastric cancer.</p><p><b>METHODS</b>Eligible patients had measurable lesions and no previous history of chemotherapy (except adjuvant chemotherapy). Oxaliplatin was administered intravenously at a dose of 130 mg/m(2) on day 1. S-1 was administered orally in doses of 80, 100, or 120 mg/d according to body surface areas of <1.25 m(2), 1.25-1.5 m(2), or >1.5 m(2) respectively; the total dose was divided into two daily doses on days 1-14. Treatments were repeated every 3 weeks until disease progression or intolerable toxicity occurred.</p><p><b>RESULTS</b>Forty-three patients were enrolled in the study. All were assessable for efficacy and adverse events. The objective response and disease control rates were 55.8% and 76.7% respectively. The median follow-up time was 16.5 months. The median progression-free survival time was 7 months (95% CI, 5.8-8.2 months) and the median overall survival time was 16.5 months (95% CI, 9.7-23.3 months). The one-year survival rate was 54.2%. Major adverse reactions were grade 3/4 neutropenia (9.3%) and thrombocytopenia (20.9%).</p><p><b>CONCLUSION</b>The SOX regimen with oxaliplatin at a dose of 130 mg/m(2) was found to be effective and safe as a first-line chemotherapy in Chinese patients with advanced gastric cancer.</p>

Analysis of prognostic factors after radical resection in 628 patients with stage II or III colon cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the clinicopathologic factors related to recurrence and metastasis of stage II or III colon cancer after radical resection.</p><p><b>METHODS</b>The clinical and pathological data of 628 patients with stage II or III colon cancer after radical resection from Jan. 2005 to Dec. 2008 in our hospital were retrospectively reviewed and analyzed.</p><p><b>RESULTS</b>The overall recurrence and metastasis rate was 28.5% (179/628). The 5-year disease-free survival (DFS) rate was 70.3% and 5-year overall survival (OS) rate was 78.5%. Univariate analysis showed that age, smoking intensity, depth of tumor invasion, lymph node metastasis, TNM stage, gross classification, histological differentiation, blood vessel tumor embolus, tumor gross pathology, multiple primary tumors, preoperative and postoperative serum concentration of CEA and CA19-9, and the regimen of adjuvant chemotherapy were correlated to recurrence and metastasis of colon cancer after radical resection. Multivariate analysis showed that regional lymph node metastasis, TNM stage, the regimen of postoperative adjuvant chemotherapy, and preoperative serum concentration of CEA and CA19-9 were independent factors affecting the prognosis of colon cancer patients.</p><p><b>CONCLUSION</b>Regional lymph node metastasis, TNM stage, elevated preoperative serum concentration of CEA and CA19-9, the regimen of postoperative adjuvant chemotherapy with single fluorouracil type drug are independent risk factors of recurrence and metastasis in patients with stage II-III colon cancer after radical resection.</p>

Association of Lipoprotein-Associated Phospholipase A2 with Characteristics of Vulnerable Coronary Atherosclerotic Plaques

PURPOSE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory enzyme expressed in atherosclerotic plaques. We investigated the association of circulating Lp-PLA2 with characteristics of vulnerable coronary atherosclerotic plaques. MATERIALS AND METHODS: We recruited 113 patients with either unstable angina (UA, n=59) and stable angina (SA, n=54) by coronary angiography. Thirty-six healthy subjects served as controls. Intravascular ultrasound (IVUS) was used to evaluate the characteristics of coronary atherosclerotic plaque, and serum Lp-PLA2 concentration was measured as well. RESULTS: Lp-PLA2 concentration was significantly higher in both UA and SA patients [(396+/-36) microg/L and (321+/-39) microg/L, respectively] compared with the controls [(127+/-49) microg/L, p<0.01], and higher in UA than SA group. IVUS findings showed that remodeling index (RI) (0.91+/-0.15 vs. 0.85+/-0.11, p=0.005) and eccentricity index (EI) (0.73+/-0.16 vs. 0.65+/-0.22, p=0.039) were larger in UA than in SA group, and fibrous caps were thicker in SA than UA group [(0.91+/-0.23) mm vs. (0.63+/-0.21) mm, p=0.032]. Moreover, Lp-PLA2 correlated positively with EI (r=0.439, p<0.01) and RI (r=0.592, p<0.05) in UA group. There was an inverse relationship between Lp-PLA2 and fibrous cap thickness in both UA (r=-0.587, p<0.001) and SA (r=-0.318, p<0.05) groups. The independent risk factors in UA group were Lp-PLA2 (OR=1.055, 95% CI: 1.03-1.08, p=0.013), LDL-cholesterol (OR=0.032, 95% CI: 0.00-0.05, p=0.041) and fibrous cap thickness (OR=0.008, 95% CI: 0.00-0.45, p=0.019). Lp-PLA2 was strongly associated with both EI and fibrous cap thickness in both groups. CONCLUSION: Serum level of Lp-PLA2 is associated with both eccentricity index and fibrous cap thickness in both UA and SA groups. Elevated levels of circulating Lp-PLA2 might to be a strong risk factor and more serious for unstable angina than stable angina.

siRNA inhibits efgl7 expression in human endothelial cell line HUVEC / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the effects of small interference RNA (siRNA) on epidermal growth factor-like domain 7 (egfl7) gene expression in human endothelial cell line HUVEC.</p><p><b>METHODS</b>siRNA targeting egfl7 (siRNA1, siRNA2, siRNA3 and siRNA4) was constructed through online design of Amnion company and transfected into human endothelial cell line HUVEC with lipofectamine. The nontransfected cells and cells treated with control siRNA were taken as controls. At 24, 48 and 72 hours post various interventions, cell viability was determined by MTS method as well as LDH and ATP releasing tests. egfl7 expressions at protein and mRNA levels were detected by Western blot and RT-PCR respectively.</p><p><b>RESULTS</b>Cell survival rate, LDH and ATP release were significantly reduced in siRNA treated cells compared to control cells (P < 0.05). Similarly, egfl7 expression at protein and mRNA levels was also significantly reduced in siRNA treated cells (P < 0.01), especially in siRNA1 treated cells.</p><p><b>CONCLUSION</b>siRNA inhibited egfl7 gene expression and cell survival in HUVEC.</p>