Objective To explore the Kano model analysis in the application of midwife outpatient service quality management. Methods Kano questionnaire was consisted of 24 items, including five parts, environment facilities, service evaluation, service technology, the team service, delivery service′quality. Using the Kano model analysis, the impact factors of the midwife outpatient service quality in five different quality attributes were determined. It included property and had the opposite answer to the question, charisma, essential properties and one property. Results By identifing the quality index classification of the pregnant women with satisfactory service quality to midwife outpatient service, attributable to a property were 1,2,3,4,8,9,10,14,20,21;attributable to mandatory attributes were 13, belonging to the charm of the property had 5,6,7,11,12,15,16,17,18,19,22,23,24. Midwives outpatient had most of charisma attribute, 54.2%(13/24) of the total;The second was one attribute, 41.7% (10/24) of the total. The technology level of midwife was essential attribute. Conclusions Kano mode analysis technology will be introduced to the midwife outpatient service quality management to provide decision reference for improving the quality of the hospital management level, improve maternal satisfaction, improve the obstetric operation efficiency.

Local focal adhesion kinase (FAK) is a non-receptor intracellular tyrosine kinase that plays an important role in tumor initiation, development, metastasis and invasion, and is considered to be an important target for the development of antineoplastic drugs. It has both kinase-dependent and non-kinase-dependent scaffolding functions. However, traditional small molecular inhibitors can only inhibit its kinase-dependent activity, so it is difficult to target the kinase-independent scaffolding function. Therefore, there is an urgent need for novel strategies to enhance FAK targeting to lay the foundation for determining the druggability and discovery of FAK inhibitors. Proteolysis targeting chimera (PROTAC) is a new drug development strategy that can recruit E3 ligase to specifically ubiquitinylate target proteins for degradation through the proteasome system. The unique mechanism of action of the PROTAC system could be used to target and degrade the FAK protein, thus eliminating the scaffolding function of FAK. In this review, FAK protein, the signaling pathway, and small molecule inhibitors are briefly described, and the latest research progress in targeting the degradation of FAK using PROTAC technology is summarized.

Objective To construct replication-deficient recombinant adenoviruses AdHNF4?that co-expresse human hepatocyte nuclear factor 4?(HNF4?) and green fluorescent protein(GFP) gene,and to evaluate the effect of HNF4?up-regulation on hepatocyte gene expression.Methods The HNF4?cDNA was obtained through RT-PCR from human hepatocyte.The recombinant adenoviral plasmid- pAdHNF4?was established using AdEasy system and packed in 293 cells.After transfection of human hepatoma cell lines HepG2 and Hep3B with AdHNF4?,the expression of HNF4?and other liver-associ- ated functional genes were evaluated by RT-PCR and Western blot.Results The recombinant plasmid pAdHNF4?was confirmed by restriction endonuclease digestion and sequencing.GFP expression was observed on the fourth day after packing the linearized pAdHNF4?in 293 cells.Stable transfection of AdHNF4?with a titer of 1?10~(10) efu/ml was obtained after repeated amplification.More than 90% of human hepatoma cells had GFP expression in 72 hours after transfection of AdHNF4?.The expression of HNF4?mRNA and protein were significantly up-regulated compared with the control group(3.4 folds in HepG2 infected with AdHNF4a and 5.2 folds in Hep3B infected with AdHNF4?).Furthermore,the transcriptional expressions of some liver-associated functional genes such as apolipoprotein,cytochrome P450 families,glutamine synthetase,phosphoenolpyruvate carboxykinase and glucose-6-phosphatase also increased after transfection of the virus,and the apoptosis ratio of the cells increased.Conclusions Up- regulating the expression of HNF4?in human hepatoma cells with AdHNF4?could enhance normal liver- specific function.Our study would provide a new idea for the researches on gene regulation of transplan- ted hepatocytes.

Objective To investigate the intervening effect of transcutaneous electrical nerve stimulation plus auricular plaster therapy on depression and self-esteem in elderly patients with coronary heart disease. Methods One hundred and twenty-eighty patients with coronary heart disease were randomized to groups A, B, C and D, 32 cases each. Group A received conventional medication and health education. In addition to those given to group A, group B received auricular plaster therapy; group D, transcutaneous electrical nerve stimulation; group C, transcutaneous electrical nerve stimulation plus auricular plaster therapy. The Hamilton Depression Scale (HAMD) score and the Rosenberg self-esteem scale (RSES) score were recorded in every group before and after treatment. Results There were statistically significant pre-/post-treatment differences in the HAMD score and RSES score in all the four groups (P<0.05, P<0.01). After the intervention, the HAMD score and RSES score in group D were significantly different from those in group A (P<0.05). Conclusion Transcutaneous electrical nerve stimulation plus auricular plaster therapy and conventional medication helps to relieve depression and raise self-esteem in elderly patients with coronary heart disease.

BACKGROUNDLiver targeting drug delivery systems can improve the curative effects and relieve the cytotoxicity of the chemotherapy drugs in the treatment of liver diseases. Nanoparticles carrying therapeutic drugs are currently under hot investigation with great clinical significance. This study was aimed to investigate the different tissue distribution of the adriamycin polybutylcyanoacrylate nanoparticle (ADM-PBCA-NP) in the mice body after an injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in different diameters on normal mice liver.

METHODSOne hundred and eighty Kunming mice were randomly divided into 6 groups with 30 mice in each group (5 treatment groups of ADM-PBCA-NP in the different diameter ranges, non-conjugated free adriamycin injection was employed as the control group). A single dose of either conjugated or free adriamycin equaled 2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30 minutes, 1, 5 and 12 hours postinjection, respectively. The adriamycin concentrations in the respectively collected liver, kidney, spleen, heart, lung and plasma were demonstrated using a high performance liquid chromatography with fluorescence detector.

RESULTSCompared with the control group, adriamycin was hardly detected in the heart muscle of the treatment groups (P < 0.05). The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissue. The adriamycin concentrations of the mice liver and spleen in the experimental groups were significantly higher than that in the control group, except for the group with the nanoparticles diameters of (22.3 +/- 6.2) nm (P < 0.05). The ADM-PBCA-NP in (101.0 +/- 20.3) nm diameter had the highest liver distribution, and the second highest adriamycin distribution in liver was the group of (143.0 +/- 23.5) nm diameter (P < 0.05). Moreover, adriamycin was released slowly in the liver during the detection period in the experimental groups. ADM-PBCA-NP in (22.3 +/- 6.2) nm diameter was not distributed in the tissue of the liver, kidney, heart, spleen, and lung.

CONCLUSIONSADM-PBCA-NP in 100 - 150 nm diameter range has the best liver targeting with a characteristic of slow medicine release. It also decreases the medicine distribution in the heart, kidney and lung. In the treatment of liver cancer, the polybutylcyanoacrylate nanoparticles system has a good liver targeting ability, which increases the anticancer activity and markedly decreases the toxicity of adriamycin.

Animals ; Antineoplastic Agents ; administration & dosage ; Doxorubicin ; administration & dosage ; Drug Delivery Systems ; Enbucrilate ; administration & dosage ; Liver ; metabolism ; Mice ; Nanostructures ; Tissue Distribution

OBJECTIVETo observe the therapeutic effects of beta-elemene combined DC/Dribble vaccine in treating mice with hepatic cancer, thus exploring their anti-tumor mechanisms.

METHODSDentritic cells were derived from Balb/c mice's spleen and their phenotypes were identified. Using hepatic cancer cell line BNL1MEA.7R.1 (abbreviated as BNL) originated from Balb/c mice as target cell, DC/Dribble vaccine was prepared via raising the antigen representing carrier autophagosomes (DRips in Blebs, DRibbles), which were rich in tumor antigen information. The mice previously immunized were divided into 4 groups, i.e., the control group, the beta-elemene group, the vaccine group, and the combined group. The PBS was subcutaneously and intraperitoneally injected to mice in the control group. The beta-elemene was intraperitoneally injected at the daily dose of 50 mg/kg to mice in the beta-elemene group and the combined group for 7 successive days. DC/Dribble vaccine was injected into the lymph node of mice in the vaccine group and the combined group on the 1st day, and DC/Dribble vaccine was subcutaneously injected on the 3rd day and the 5th day. All the mice were sacrificed on the 10th day. Their spleens were obtained sterilely, and the suspension was incubated with or without Dribble. The cells were inoculated for 72 h. The contents of IFN-gamma in the supernatant were measured by ELISA. In addition, the spleen cells obtained from the combined group were incubated with different stimulations for 72 h, which were then divided into the control group, the DRibble group, the DC group, and the DC/Dribble vaccine group. The supernatant of cultured cells were collected and the contents of IFN-gamma were measured by ELISA. The liver tumor-bearing mouse model was established, and then the BNL bearing mice were randomly divided into 4 groups, i.e., the control group, the beta-elemene group, the vaccine group, and the combined group. The treatment ways were the same as the immune ways. The tumor size and the survival period were observed in each group. On the 23rd day the mice were sacrificed. The tumor tissue was stripped and stained by HE staining. The pathomorphological manifestations of the tumor tissue were observed by light microscope.

RESULTSIn vitro detection of mice immunized previously by different ways showed that the secretion of IFN-gamma was significantly higher in the combined group than in the rest groups (P < 0.01). The secretion of IFN-gamma was significantly higher in the beta-elemene group and the vaccine group than in the control group (P < 0.01). The spleen cells could be stimulated to secrete a large amount of IFN-gamma in the vaccine group and the Dribble group (P < 0.01). When the beta-elemene was 10 microg/mL as the stimulating dose, the secretion of IFN-gamma obviously increased (P < 0.01). In vivo observation showed that the growth velocity of tumors in mice of the combined group was slowed down. There was statistical difference in the tumor area or the survival period of mice in the combined group, when compared with the other groups (P < 0.01). In HE staining, the surrounding connective tissues of the tumor were wrapped tightly and compactedly, with infiltration of a large amount of inflammatory cells.

CONCLUSIONSbeta-elemene combined DC/Dribble vaccine could induce specific immune cells to secrete secretory cells, thus exerting its anti-tumor effect. Its immunological effects might be associated with enhancing the DC antigen presenting function.

Animals ; Cancer Vaccines ; immunology ; Cell Line, Tumor ; Dendritic Cells ; drug effects ; immunology ; Female ; Liver Neoplasms ; drug therapy ; immunology ; Mice ; Mice, Inbred BALB C ; Sesquiterpenes ; pharmacology

OBJECTIVETo evaluate the relationship between plasma trough level of imatinib and clinical outcomes in Chinese CML patients.

METHODSPlasma trough levels in 416 CML patients who received imatinib orally in six general hospitals were assessed. The correlations of imatinib plasma trough level with baseline characteristics including age, weight and BSA, and clinical response were evaluated.

RESULTS(1) Effects of age, body weight and BSA on imatinib plasma trough levels were not to be clinically significant. (2) Median imatinib plasma trough levels was 1271 (109-4329). Imatinib plasma trough level was related to dose of imatinib administration. Plasma trough levels at imatinib of dose < 400, 400 and > 400 mg were (969 ± 585), (1341 ± 595) and (1740 ± 748) µg/L (P < 0.01), respectively. (3) There was no statistic difference in imatinib plasma trough level with complete cytogenetic response [CCyR (1337 ± 571) µg/L vs no CCyR (1354 ± 689) µg/L, P = 0.255]. (4) Imatinib plasma trough level might be important for a good clinical response in some CML patients.

CONCLUSIONThere was a large interpatient variability in imatinib plasma concentration in Chinese CML patients. No correlation of imatinib plasma trough level with CCyR was observed. However, higher doses of imatinib were shown to attain greater trough plasma concentration, suggesting that imatinib plasma trough level might be important for a good clinical response in some CML patients.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Benzamides ; blood ; therapeutic use ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; drug therapy ; Male ; Middle Aged ; Piperazines ; blood ; therapeutic use ; Pyrimidines ; blood ; therapeutic use ; Treatment Outcome ; Young Adult

Objective To evaluate the diagnostic value of endoscopic ultrasonography (EUS) in staging of rectal cancer (RC).Methods From January 2015 to January 2017,the clinical data of 204 patients with RC and received EUS and surgery were retrospectively analyzed.Patients were divided into surgery alone group (155 cases) and preoperative neoadjuvant chemoradiation therapy (CRT) plus surgery group (49 cases).The preoperative staging by EUS and postoperative pathological staging of two groups were compared.Kappa test was performed for statistical analysis.Results Compared with postoperative pathologic diagnosis,the accuracy rate of EUS in the evaluation of invasion depth of RC in surgery alone group was 81.9％ (127/155),and the accuracy rates in the diagnosis of Tis,T1,T2,T3 and T4 were 3/4,11/13,82.1％(32/39),91.1％(41/45) and 74.1％(40/54),respectively,with a good consistency (kappa=0.751,P＜0.01).However,the accuracy rate of EUS in the invasion depth of RC in CRT plus surgery group was 34.7％ (17/49),and the accuracy rates in the diagnosis of T2,T3 and T4 were 1/13,2/7 and 14/16,respectively,with a poor consistency (kappa =0.107,P=0.850).Compared with postoperative pathologic diagnosis,the diagnostic accuracy rate of EUS in evaluating regional lymph node metastasis in surgery alone group was 70.3％ (109/155),and the accuracies in the diagnosis of cases with or without regional lymph node metastasis were 40.7％ (24/59) and 88.5％ (85/96),respectively,with a poor consistency (kappa=0.317,P＜0.01).The diagnostic accuracy rate of EUS in evaluating regional lymph node metastasis of preoperative CRT plus surgery group was 51.0％ (25/49),and the accuracies in the diagnosis of cases with or without regional lymph node metastasis were 5/11 and 52.6％ (20/38),respectively,with a poor consistency (kappa =0.014,P =0.911).Conclusions EUS can accurately evaluate the depth of tumor invasion and lymph node metastasis in preoperative staging of RC,which may be helpful for determining clinical treatment strategy.However,for patients received CRT treatment,EUS has a limited value in diagnosing and staging the tumor.

Objective To measure the transaction costs of compact county medical alliance and propose counter-measures.Methods Based on Williamson-Zhang Wuchang analysis paradigm,it established the measure matrix of transaction cost of compact county medical alliance.Through the typical sampling method,the medical community of D city in Haixi Prefecture,Qinghai Province was selected as a research example to carry out an empirical study.Results The total transaction cost of the compact county medical community was 6 292 500.00 yuan,the transac-tion cost of the leading hospital was 6 234 300.00 yuan,accounting for 99.07％,and the special investment of the leading hospital reached to 5 887 100.00 yuan,accounting for 94.43％.The total transaction cost of the 298 referred patients was 308 400.00 yuan,and the average transaction cost per patient was 1 035.05 yuan.Conclusion The transaction costs of compact county medical alliance was generally high,most of which was borne by the leading hospital,and the patients also had to bear the corresponding transaction costs.In the next stage,the transaction costs should be dealt with from three aspects,including recognizing the secrecy and universality of the transaction costs,establishing economical system supply and establishing a sound compensation mechanism.

Objective To measure the transaction costs of compact county medical alliance and propose counter-measures.Methods Based on Williamson-Zhang Wuchang analysis paradigm,it established the measure matrix of transaction cost of compact county medical alliance.Through the typical sampling method,the medical community of D city in Haixi Prefecture,Qinghai Province was selected as a research example to carry out an empirical study.Results The total transaction cost of the compact county medical community was 6 292 500.00 yuan,the transac-tion cost of the leading hospital was 6 234 300.00 yuan,accounting for 99.07％,and the special investment of the leading hospital reached to 5 887 100.00 yuan,accounting for 94.43％.The total transaction cost of the 298 referred patients was 308 400.00 yuan,and the average transaction cost per patient was 1 035.05 yuan.Conclusion The transaction costs of compact county medical alliance was generally high,most of which was borne by the leading hospital,and the patients also had to bear the corresponding transaction costs.In the next stage,the transaction costs should be dealt with from three aspects,including recognizing the secrecy and universality of the transaction costs,establishing economical system supply and establishing a sound compensation mechanism.