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Objective:To investigate the predictive ability of Glypican-3 (GPC3) positive hepatocellular carcinoma based on the hepatobiliary specific contrast agent gadoxetate disodium enhancement of the liver imaging reporting and data system version 2018 (LI-RADS v2018) imaging features, and to assess the relevant clinical imaging features for postoperative recurrence in GPC3 positive HCC patients.Methods:This study was a cohort study. A total of 122 hepatocellular carcinoma patients who underwent gadoxetate disodium enhanced MRI examination with hepatic tumor resection in Henan Provincial People′s Hospital from January 2017 to December 2021 were retrospectively collected, including 96 GPC3 positive and 26 GPC3 negative patients. The imaging features defined by LI-RADS v2018 of HCC lesions were analyzed. Patients were followed up for 40 months to determine recurrence free survival (RFS). The logistic regression was used to analyze the risk factors of GPC3 positivity. An imaging model, and a clinical-imaging model which combined the patient′s alpha-fetoprotein levels were constructed. The efficacy of the model for predicting GPC3 positivity was assessed using receiver operating characteristic curves. Kaplan-Meier method was used to draw the survival curve, and the log-rank test was used to compare the RFS between GPC3 positive and negative patients. Risk factors affecting the recurrence of GPC3 positive HCC were assessed by Cox regression.Results:The results of logistic multivariate regression analysis confirmed that rim enhancement ( OR=5.685, 95% CI 1.229-26.287, P=0.026) and irregular tumor margin at hepatobiliary phase ( OR=4.431, 95% CI 1.684-11.663, P=0.003) were independent risk factors for GPC3 positive HCC. The area under the curve for predicting GPC3 positivity was 0.745 (95% CI 0.636-0.854) for the imaging model and 0.776 (95% CI 0.677-0.876) for the clinical-imaging model. The mean RFS in the GPC3 positive group was 22 months, and it was 32 months in the negative group. There was a statistically significant difference in RFS between the two groups ( χ2=5.15, P=0.023). The multivariate Cox regression analysis showed that the arterial rim enhancement ( HR=5.460, 95% CI 1.966-15.162, P=0.001), microvascular invasion ( HR=2.402, 95% CI 1.210-4.769, P=0.012), portal vein tumor thrombus ( HR=3.226, 95% CI 1.114-9.344, P=0.031) were independent risk factors for recurrence after hepatic tumor resection for GPC3-positive HCC. Conclusions:A model based on the LI-RADS v2018 imaging features of hepatobiliary specific contrast agent gadoxetate disodium enhancement can effectively predict GPC3 positive HCC. The arterial rim enhancement, microvascular invasion and portal vein tumor thrombus are independent risk factors for postoperative recurrence of GPC3 positive HCC.
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The integration of regional medical centers and community health service centers is an effective way to improve the professional ability of general practitioners in post-practice training. Its major advantage lies in the establishment of a regional general practitioner ability improvement system integrating assessment, practice and teaching under the unified health administrative department. This article introduces the path of general practitioner post-training developed by Shanghai Tongren Hospital in forms of a regional medical center combined with the community health service center under the "integrated dual-drives" model, which was carried out in Shanghai Changning District; and its preliminary accomplishment is also discussed. It may provide reference for regional medical centers to improve the ability of general practitioners through practice-driven and teaching-driven.
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Objective:To analyze the clinical knowledge and training needs of general practitioners from subjective perception and objective assessment, and to analyze their relationship.Methods:A survey was conducted among general practitioners from community health service centers in Shanghai Changning district from September to December 2020. Based on the general practitioner competency indicator system designed by the project team, 17 clinical knowledge competency evaluation indicators were developed through expert consultation, and used for subjective perception and objective assessment of clinical knowledge and learning needs among general practitioners. The influencing factors of objective assessment scores were analyzed, and the relationship between subjective perception and objective assessment scores was analyzed using the four quadrant method.Results:A total of 136 general practitioners participated in the study with the mean age of (39.25±5.90) years, most of whom were attending physician (67.65%, 92/136) and had undergraduate education (88.20%, 122/136). The average daily application frequency score was (1.55±0.21), and the training needs score was (1.65±0.09) for 17 clinical knowledge items; the average objective evaluation score was (74.21±14.0) points. The older the age ( OR=1.25, 95% CI:1.14-1.37), the higher the educational level ( OR=2.11, 95% CI:1.57-2.83), and the longer the working years ( OR=1.16, 95% CI:1.04-1.30) were significantly correlated with the higher objective evaluation scores (all P<0.05). The objective evaluation scores of endocrine diseases such as diabetes, cerebrovascular diseases and respiratory diseases are the highest, and the daily application frequency and learning needs are high (the first quadrant); The objective evaluation scores of common orthopedic diseases, common psychological diseases, and planned immunity indicators were relatively low, but their daily application frequency and learning needs were relatively high (second quadrant). The objective evaluation scores of indicators such as common malignant tumors, common dermatology diseases and health problems, and common ENT diseases were low, and the daily application frequency and learning needs were also low (the third quadrant). The objective evaluation scores of indicators such as hospice and palliative care are relatively high, but their daily application frequency and training needs are relatively low (listed in the fourth quadrant). Conclusions:The clinical knowledge levels of general practitioners are correlated with age, education level, and years of practice. There is a certain overlap between the objective evaluation results of clinical knowledge and the frequency of knowledge usage and training needs of general practitioners, and a targeted training mechanism should be established.
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Objective:To construct an evaluation scale for post competence of family doctors based on knowledge-skill-management model.Methods:The evaluation dimensions and indicators for post competency of family doctors were preliminarily developed through literature review, internal group meeting and brainstorming, and in-depth interviews of experts. And 16 experts in the fields of general practice and health management were invited for 2 rounds of Delphi consultation from December 2020 to April 2021. A competency evaluation scale for family doctors based on the dimensions of knowledge, skills and management was finally constructed.Results:The age of the experts was (47.9±7.3) years with a working experience of (24.6±7.8) years. The Cronbach′s α of the questionnaires was 0.891 and the KMO was 0.844. The positive coefficients for 2 rounds of expert consultation were 100%; the familiarity level of experts was 0.86 and authority level was 0.89 in the first round consultation, and those were 0.84 and 0.90 in the second round consultation. After 2 rounds of consultation, the coordination coefficient of expert opinions in the knowledge and skill dimensions was>0.5, and that in the management dimension and overall evaluation system was>0.3. After discussion 2 indicators were deleted in the first round of consultation. The finally constructed family doctor post competency evaluation scale included 3 dimensions, 8 secondary indicators and 61 tertiary indicators. Conclusion:Through the Delphi consultation, we have successfully constructed an evaluation scale for post competence of family doctors based on the three dimensions of knowledge, skills and management.
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AIM: To observe the clinical efficacy of Fuzheng Xiaoliu Granules in the treatment of stage II primary liver cancer and to explore its mechanism of action from the perspective of metabolomics. METHODS: Sixty patients with stage II primary liver cancer who achieved complete remission (CR) after comprehensive interventional therapy were randomly divided into treatment group and placebo group, with 30 patients in each group. They were treated for one year and observed for one year. The one-year recurrence rate, traditional chinese medicine (TCM) syndrome score, alpha-fetoprotein and child-pugh grade were compared between the two groups. The serum metabolites of the two groups before and after treatment were screened by ultra-high liquid chromatography-mass spectrometry technology, and the metabolic pathways and related biological pathways were analyzed. RESULTS: The one-year recurrence rate of the treatment group was significantly lower than that of the placebo group, and the overall improvement rate of TCM syndrome score was significantly better than that of the placebo group (P0.05). Metabolomics results showed that there were 39 and 33 different metabolites in the treatment group before and after treatment and in the two groups after treatment, respectively. After enrichment analysis and topological analysis of the different metabolites, it was found that Fuzheng Xiaoliu Granules could affect amino acid metabolism, fatty acid metabolism and purine metabolism and other metabolic pathways. Before and after treatment in the treatment group and after treatment in the two groups, there were the same differential metabolites and metabolic pathways in the two comparison results. The same differential metabolites with FOLD CHANGE>1 include Stearic acid, Hypoxanthine, Kynurenic acid, Arachidonic acid, and N-Arachidonoyl Dopamine. The same metabolic pathways with Impact>0.1 include Arachidonic acid metabolism and Histidine metabolism. CONCLUSION: Fuzheng xiaoliu granules can effectively reduce the recurrence rate of stage II liver cancer patients after comprehensive intervention and improve the TCM syndrome. It may inhibit the activation of PI3K/Akt and ERK signaling pathways by regulating the content of metabolites involved in metabolic pathways such as amino acids and fatty acids, thereby delaying tumor recurrence.
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Objective:To develop an occupational internal driving force measurement scale for general practitioners receiving residency training, and to investigate its reliability and validity.Methods:A pool of items was constructed for the scale based on the literature analysis and qualitative interview results of occupational internal driving force and the current development status of general practitioners, and then expert Delphi consultation was conducted to form the initial version of the scale. A questionnaire survey was conducted among 403 general practitioners to test the reliability and validity of the scale.Results:There were 11 items in the occupational internal driving force scale for general practitioners receiving residency training, which were divided into three dimensions. The scale had a Cronbach's α coefficient of 0.945, and each dimension had a Cronbach's α coefficient of above 0.850; the KMO coefficient of the Bartlett's sphericity test was 0.925. The factor analysis showed that all items had a factor load of ≥0.4 and a commonality of >0.2, and thus 11 items were retained. Three common factors were extracted by the factor analysis and the correlation analysis showed a correlation coefficient of >0 between the common factors of the total score of the scale and a significant positive correlation ( P<0.01). Based on the contents, theoretical research, and expert suggestions of each factor, they were named subject affiliation, development expectations, and identification needs, which contained 3 items, 3 items, and 5 items, respectively. Conclusions:The occupational internal driving force scale for general practitioners receiving residency training has a reasonable structure and good reliability and validity and is suitable for evaluating the occupational internal driving force of general practitioners, which provides guidance for the vocational education of residents.
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Objective:To investigate the effect of low-frequency ultrasound combined with hydroxychloroquine (HCQ) on the growth and invasion of 4T1 breast cancer in mice.Methods:4T1 cells in logarithmic growth phase were divided into 4 groups: control group, ultrasound group, HCQ group and ultrasound combined with HCQ group. Western blot was performed to detect the effects of ultrasound combined with HCQ on the protein expression levels of autophagy-related proteins LC3, p62 and matrix metalloproteinase 9 (MMP-9). Transmission electron microscopy was used to observe the formation of autophagic vesicles. The cell proliferation and cell viability were determined by EdU and CCK-8. Transwell assay was performed to detect the effect of ultrasound combined with HCQ on the invasive ability of 4T1 cells. Flow cytometry was performed to detect the effect of ultrasound combined with HCQ on the apoptosis of 4T1 cells. The transplantation tumor model of 4T1 breast cancer in BALB/c mice was constructed.The mice were randomly divided into 4 groups ( n=5 for each group), including control group, ultrasound group, HCQ group, ultrasound combined with HCQ group. The tumor volume and mice body weight were evaluated and measured in each group every 2 days. Results:The expression of LC3-Ⅱ and p62 protein levels increased in the ultrasound combined with HCQ group, and intracellular autophagosome accumulation was evident by transmission electron microscopy. In cellular experiments, compared with the other groups, the ultrasound combined with HCQ group showed stronger growth inhibition, significantly decreased cell proliferation rate, decreased expression of MMP-9, and significantly inhibited invasion (all P<0.050). In the in vivo experiments, compared with the control group, the tumor growth rate of all 3 inter vention groups of mice decreased (all P<0.050), and the ultrasound combined with HCQ group had better therapeutic effects than the ultrasound and HCQ groups. The treatment effect of ultrasound combined with HCQ group was better than that of ultrasound and HCQ groups (all P<0.001). Conclusions:The combination of low-frequency ultrasound and hydroxychloroquine could synergistically inhibit tumor cell proliferation, promote apoptosis, and significantly inhibit tumor growth in 4T1 tumor-bearing mice.
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Objective:To detect the changes of liver stiffness before and after chemotherapy in postoperative breast cancer patients using the two-dimensional shear wave elastography (2D-SWE) technique, and analyze its correlation with liver serum indexs, then discuss the application value of 2D-SWE technique in the quantitative diagnosis for chemotherapeutic liver injury.Methods:Sixty breast cancer patients underwent postoperative chemotherapy in Qilu Hospital of Shandong University from January 2021 to November 2021 were included. Conventional two-dimensional ultrasound, 2D-SWE and the serum tests including alanine aminotransferase(ALT), aspartate aminotransferase(AST), γ-glutamyltransferase(γ-GT), alkaline phosphatase(AKP) were performed before and after chemotherapy, respectively. The medians of ElastQ Imaging stiffness (EQI meds) of the whole liver and different liver segments (S4, S5/S6, S7/S8) before and after chemotherapy were measured and compared. The EQI meds of different liver segments (S4, S5/S6, S7/S8) after chemotherapy were compared. The correlation between EQI med of the whole liver and serum indexes after chemotherapy was analyzed. Results:①Compared with before chemotherapy, the EQI meds of the whole liver and different liver segments after chemotherapy were significantly decreased ( P<0.001, respectively). ②The EQI meds among different liver segments were different after chemotherapy ( F=7.489, P=0.001). Moreover, the EQI meds of S5/S6 and S7/S8 were significantly lower than those of S4 after chemotherapy ( P=0.002, 0.001). ③The EQI med of the whole liver was negatively correlated with ALT, AST, and γ-GT ( r=-0.776, P<0.001; r=-0.656, P<0.001; r=-0.428, P=0.010), while there was no correlation between the EQI med of the whole liver and AKP ( r=-0.146, P=0.267). Conclusions:2D-SWE is expected to be a new, real-time, noninvasive and quantitative method to evaluate the changes of liver stiffness before and after chemotherapy in postoperative patients, thus provides a promising method for the early clinical diagnosis of chemotherapy-induced liver injury in breast cancer patients.
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Objective:To evaluate the value of quantitative analysis of the relative signal intensity (SI) of liver gadolinium disodium enhanced MRI in the grading of liver fibrosis.Methods:From January 2018 to October 2020, the relevant data of 131 patients who underwent gadoxetate disodium enhanced MRI examination were retrospectively analyzed in Henan Provincial People′s Hospital. All patients had histopathological results. According to the Laennec grading system of liver fibrosis, the patients were classified in F0-F1 (27 cases), F2 (19 cases), F3 (17 cases) and F4 (68 cases). The signal intensity of the liver, erector spinae and spleen were measured before and after the enhancement; and 5 post-contrast relative SI parameters were calculated, including the relative enhancement (RE), liver-to-muscle contrast ratio (LMC), liver-to-spleen contrast ratio (LSC), LMC increase rate, LSC increase rate. The differences of 5 post-contrast relative SI parameters among the different fibrosis grades were compared using one-way analysis of variance. The receiver operating characteristic (ROC) curves were drawn to evaluate the diagnostic efficacy of 5 post-contrast relative SI parameters in the diagnosis of clinically significant liver fibrosis (F2-F4), advanced liver fibrosis (F3-F4) and liver cirrhosis (F4).Results:The differences of RE, LMC, LSC, LMC increase rate, LSC increase rate among different liver fibrosis grades were statistically significant (all P<0.001). With the increasing of the degree of liver fibrosis, the RE, LMC increase rate and LSC increase rate showed decreased. ROC results showed that the area under the curve (AUC) of RE, LMC increase rate, LSC increase rate in diagnosing liver fibrosis in all levels were greater than those of LMC and LSC. The AUC values of RE, LMC increase rate, LSC increase rate in the diagnosis of significant fibrosis (F2-F4) were 0.89, 0.86, 0.83, with the sensitivity as 81.7%, 71.2%, 81.7%, and the specificity as 96.3%, 85.2%, and 74.1%, respectively. The AUC values of RE, LMC increase rate, LSC increase rate in the diagnosis of advanced liver fibrosis (F3-F4) were 0.93, 0.88, 0.86, with the sensitivity as 84.7%, 72.9%, 91.8%, and the specificity as 91.3%, 87.0 %, 71.7%; and the AUC values for diagnosing liver cirrhosis (F4) were 0.92, 0.86, 0.85, with the sensitivity as 82.4%, 76.5%, 92.7%, and the specificity as 88.9%, 81.0%, 65.1%, respectively. Conclusion:Gadoxetate disodium enhanced MRI relative SI parameters including RE, LMC increase rate and LSC increase rate might be used as a useful imaging marker in liver fibrosis grading.
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Objective:To investigate the clinical features, diagnosis and treatment of febrile infection-related epilepsy syndrome.Methods:The data of 3 children with febrile infection-related epilepsy syndrome admitted to the First Affiliated Hospital of Zhengzhou University from May to June 2019 were collected retrospectively, and their clinical characteristics, diagnosis, treatments and prognosis were summarized in combination with relevant literature.Results:The age of onset was 6-9 years old.The time interval from fever to first convulsion was 4-7 days, and they progressed to status epilepticus within 24 hours.The seizures were mainly multifocal seizures.Cerebrospinal fluid laboratory examination was normal.Electrocardiogram shows diffuse slow wave activity as the background, and epileptic waves dominated by the temporal area.Cranial magnetic resonance imaging showed signs of edema in 2 cases during the acute phase.All patients were resistant to multiple (4-5) anti-epileptic drugs, but high-dose anesthetic drugs can effectively terminate status epilepticus.All cases developed into refractory epilepsy, 2 cases had cognitive impairment and 1 case had movement impairment after 1 year.Conclusion:Febrile infection-related epilepsy syndrome often occurs in school-age children who have been physically healthy, which was included by fever.The seizures are explosive and refractory in febrile infection-related epilepsy syndrome, and it lacked specific laboratory indicators.High-dose anesthetics can effectively terminate status epilepticus, but it always has a poor prognosis.
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Objective:To evaluate the effect of inhibition of interleukin-6 (IL-6) trans-signaling on sepsis-associated encephalopathy (SAE) in mice.Methods:Eighty healthy male C57BL/6J mice, aged 8-10 weeks, weighing 22-24 g, were divided into 4 groups using a random number table method: sham operation group (Sham group, n=10), SAE group ( n=35), SAE plus sgp130Fc group ( n=25) and sgp130Fc group ( n=10). Sepsis was induced by cecal ligation and puncture (CLP) in anesthetized animals.Sham and sgp130Fc groups received no CLP.In group sgp130Fc and group SAE+ sgp130Fc, sgp130Fc 0.5 mg/kg was intraperitoneally injected at 1 h after sham operation or CLP.The survival rates, body weight and neurological function scores were recorded within 1-10 days after sham operation or CLP.Four mice in each group were selected at 24 h after sham operation or CLP to detect the expression of occlusin in hippocampus by Western blot.Five mice in each group were selected to measure cognitive function using Morris water maze test at day 4 after sham operation or CLP. Results:Compared with group Sham, the survival mice, body weight and neurological function scores on days 2-10 after CLP were significantly decreased, the expression of occludin was down-regulated, the frequency of crossing the original platform was decreased, and the time spent in target quadrant was shortened in group SAE ( P<0.05), and no significant change was found in the indexes mentioned above in group sgp130Fc ( P>0.05). Compared with group SAE, the survival rate and neurological function scores on days 3-10 after CLP were significantly increased, the expression of occludin was up-regulated, the frequency of crossing the original platform was increased, and the time spent in target quadrant was prolonged ( P<0.05), and no significant change was found in body weight in group SAE+ sgp130Fc ( P>0.05). Conclusions:Inhibition of IL-6 trans-signaling can reduce the damage to the blood brain barrier and SAE in mice.
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Retrospective analysis of the clinical data of a child with type 102 mental retardation caused by DDX3X gene mutation in the pediatric diagnosis of the First Affiliated Hospital of Zhengzhou University in April 2019.A 2 years and 3 months old girl with " delay for more than 1 year" , using second-generation sequencing technology for full exon detection, and the result is DDX3X gene 13 th exon c. 1463G>A hybridization mutation, this is a new mutation.There are no Chinese cases reported with DDX3X gene mutations, and there are 8 related cases were reported in foreign literature, all children have different degrees of intellectual disability.So patients with unexplained intellectual disability(especially female patients) need to be wary of the possibility of DDX3X gene mutation.
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Muscarinic acetylcholine receptor (M-AChR) is a type of cholinergic receptor. In recent years, there have been many studies on the mechanism of various types of M-AChR in depression. Therefore, this review intends to focus on M-AChR related mechanisms in the onset and treatment of depression, and the research of related drugs is summarized and prospected. The results show that M1-AChR and M2-AChR play important roles in antidepressant, and its possible mechanism involves the mammalian target of rapamycin complex 1 (mTORC1) signal pathway activation in the hippocampus and prefrontal cortex (PFC), release of excitatory neurotransmitter and brain-derived neurotrophic factor (BDNF) and other factors, at the same time protein kinase A -α-amino the activation of the α-amino-3-hydroxy-5-methylisoxazole-4-propionieacid (AMPA) pathway plays an important regulatory role in the antidepressant effect mediated by M2-AChR, but the specific mechanisms and the interactions between various type of M-AChR are still to be explored, which may also become the focus of future research. At present, clinical trials of related drugs are mainly focused on scopolamine. With the progress of clinical trials, the dose-effect curve and side effects tolerance of scopolamine will be more clearly and it is believed that more patients can benefit from it.
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From March 2019 to May 2019, panel interviews were conducted with 39 representatives of 10 community health service centers in Shanghai Changning District, each took 30 to 90 min. The relevant information of interviews was coded, classified, streamlined, and the interview topics were sorted out. The interviews showed the following problems of continuing education in community health care setting currently: there were lack of updated disease-related clinical guidelines and other knowledge, lack of uniform regulations on rational drug use; the contents or forms of training did not match the needs of the community; and training in psychology and nutrition therapy could not be transformed into practical application. The participants made the following suggestions for continuing medical education: to build a database of clinical guidelines for diseases; to provide information-based support and guidance for rational drug use; to design training contents and training forms based on community needs; to provide training support in psychology, nutrition and other subjects; to increase trainings in research, teaching and health management and other aspects. Continuing medical education for community general practioners faces problems from knowledge users, knowledge providers, and the policy environment. The contents and forms of training needs should be optimized. These can be strengthened by communicating with the community and following up with the needs of the community in establishing diversified training forms, supporting assessment and incentive mechanisms for different types of training contents.
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Based on literature analysis and conference discussion, the index system of the competence and performance of general practitioners (GPs) was developed, which consisted of 4 dimensions and 59 indicators. Based on the indicator system, the questionnaire was designed. From March 2019 to May 2019, a questionnaire survey on the ability, performance and training needs of GPs was conducted among the managers of 10 community health service centers in Shanghai Changning District. The dependent variables were analyzed through descriptive analysis, correlation analysis and quadrant mapping methods. The median of overall evaluation score of the performance of GPs in 10 community health service center was 2.7(2.4,2.9); and the mean of training demand score was (1.4±0.5). The performance scores was negatively correlated with the degree of training needs ( r=-0.654, P<0.01). Among the 59 capacity assessment indicators, there were 25 (42.4%) with poor performance but high training demand. The overall ability of general practitioners was common from the perspective of the community health service center managers, suggesting that it is important to strengthen the capacity development for community GPs, and those with poor performance and high training needs should be included in training priority, such as disease diagnosis and treatment, emergency management ability, rehabilitation service ability and medical law.
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Comprehensively and continuously improving the ability is the goal of continuing medical education for practicing general practitioners (GPs). It is urgent to carry out systematic planning for improvement of the training content, training methods and evaluation methods in current continuing education system. Therefore, based on the survey of the training requirements of the community GPs in Shanghai Changning District, this study proposed a pathway of establishing continuing education mechanism for community GPs in regional medical centers. This continuing education mechanism planned to build a talent evaluation system reflecting the competency of the community GPs, to develop training contents based on the community situation and the needs of the GPs, to establish the practice support and the collaboration platform of science, education and research, to promote the sustaining improvement of GPs.
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Objective To investigate the selective targeting ability of a novel folate-modified nanobubbles with two-fold amount of folate [(FOL)2-NBs] . Methods DSPE-PEG2000-AD-(FOL)2with two-fold of folate per DSPE-PEG2000 chain was synthesized and then tested by 1 H nuclear magnetic resonance (1H NMR) . The novel (FOL)2-NBs was prepared using the mechanical shaking method based on lipid-stabilized perfluoropropane . The bubble size was measured by Malvern laser particle size analyzer and the contrast enhancement ability was also detected with imaging machine using a self-made agarose mold . The experiment of selective targeting ability was also carried out in human breast cancer MCF-7 cell with over-expression of folate receptor ( FR) using fluorescence activated cell sorting ( FACS) . Results The result of 1H NMR proved that DSPE-PEG2000-AD-( FOL )2was successfully synthesized ,and the purity reached up to 90% . The novel prepared ( FOL) 2-NBs showed superior contrast enhancement ability with a particle size of ( 286 .87 ± 22 .96) nm . Compared with the conventional NBs ,the novel ( FOL) 2-NBs exhibited improved selective cellular targeting ability proven by FACS . Conclusions A novel nanobubble with improved selective targeting ability is successfully prepared and shows great potential in extravascular imaging and curation in FR overexpressed tumors .
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Objective To evaluate the effect of methylprednisolone on endoplasmic reticulum stress in rats with ventilator-induced lung injury ( VILI ) and the relationship with phosphatidylinositol 3-kinase∕serine-threonine protein kinase ( PI3K∕Akt) signaling pathway. Methods One hundred clean-grade male Sprague-Dawley rats, aged 4-5 months, weighing 270-320 g, were divided into 5 groups ( n=20 each) using a random number table method: control group ( C group) , VILI group ( V group) and different doses of methylprednisolone groups ( M1-3 groups) . Group C received no mechanical ventilation and kept spontane-ous breathing for 4 h. Rats were mechanically ventilated ( tidal volume 40 ml∕kg, respiratory rate 15-17 breaths∕min, inspiratory∕expiratory ratio 1 : 1, positive end-expiratory pressure 0, fraction of inspired oxy-gen 21% during OLV) in group V. Methylprednisolone 2, 10 and 30 mg∕kg were intravenously injected at 20 min before mechanical ventilation in M1-3 groups, respectively, and the equal volume of normal saline was given in group V. Blood samples and lung tissues were taken at 4 h of ventilation for measurement of the lung permeability index ( LPI) and wet∕dry lung weight ratio ( W∕D ratio) , for examination of pathological changes, and for determination of apoptosis index ( AI) in lung tissues ( by TUNEL) , expression of Akt, phosphorylated Akt (p-Akt), glucose-regulated protein 78 (GRP78), CCAAT∕enhancer-binding protein homologous protein (CHOP) and caspase-12 in lung tissues (by Western blot). Injured alveoli rate (IAR) was calculated. Results Compared with group C, the W∕D ratio, LPI, IAR and AI were significantly in-creased, the expression of p-Akt was down-regulated, and the expression of GRP78, CHOP and caspase-12 was up-regulated in V and M1 groups ( P<0. 05) , and no significant change was found in the indexes mentioned above in M2 and M3 groups ( P>0. 05) . Compared with group V, the W∕D ratio, LPI, IAR and AI were significantly decreased, p-Akt expression was up-regulated, and the expression of GRP78, CHOP and caspase-12 was down-regulated in M2 and M3 groups ( P<0. 05) . Conclusion Methylprednisolone in-hibits endoplasmic reticulum stress, thus inhibiting cell apoptosis, and the mechanism is related to activa-ting PI3K∕Akt signaling pathway in rats with VILI.
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Objective To explore the bioeffect of different parameters on 4 cell lines by ultrasoundmediated microbubble destruction.Methods The orthogonal experimental design was used to investigate the effect of three factors on the bioeffects of four cell lines under three levels.Three factors included microbubble concentration,sound intensity,irradiation time.Human breast tumor (MCF-7) cells,ovarian tumor (A2780) cells,liver tumor (Bel7402) cells and thyroid tumor (ARO) cells were exposed to ultrasound in the presence of SonoVue.The cell survival rate was determined by MTT methods and the cell luminosity factor was detected by flow cytometry.Results The optimum parameters for Bel7402 and ARO cell were the same (A2B3C2),and they were different from those from MCF-7 (A3B1C1) and A2780 (A1B3C3) cell.The cell survival rates for 4 cell lines were above 75%,and the cell luminosity factors were different among 4 cell lines.Conclusions The optimum parameters by ultrasound-mediated microbubble destruction for different cell lines are different,and under the optimum parameters the bioeffects of different cell lines are different.
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Objective To investigate the relationship between the expression of imprinted gene CDKN1C in placenta and the birth weight of neonates.Methods Twenty-nine term small for gestational age (SGA) neonates admitted to Peking University Third Hospital from January 1,2014 to December 31,2014 were recruited,and 29 appropriate for gestational age (AGA) neonates with a difference of not more than one week in gestational age served as controls.Fresh placental tissue was collected and the expression of imprinted gene CDKN1C mRNA in the placenta were detected by real-time fluorescence quantitative-polymerase chain reaction,and its protein expression was estimated by Western-blot.Chi-square test,independent-sample t test,Pearson's correlation analysis were used for statistical analysis.Results The CDKN1C mRNA expression level in SGA was significantly higher than that in AGA (0.133± 0.059 vs 0.100±0.046,t=2.401,P=0.020),so was the CDKN1C protein expression (0.280±0.043 vs 0.190±0.041,t=8.410,P=0.000).The CDKN1C mRNA expression levels were negatively correlated with birth weight in both groups (SGA group,r=-0.587,P=0.001;AGA group,r=-0.569,P=0.001),and the correlation was slightly stronger in SGA (r2=0.344) than in AGA (r2=0.324).The CDKN1C protein expression levels of the two groups were negatively correlated with birth weight (SGA group,r=-0.579,P=0.001;AGA group,r=-0.497,P=0.006),the correlation being stronger in SGA group (r2=0.335) than in AGA group (r2=0.247).The CDKN1C mRNA and protein expression levels of the two groups were negatively correlated with birth weight for gender,especially in males [mRNA:r2=0.293(male)vs r2=0.185(female);protein:r2=0.730 (male) vs r2=0.601(female)].Neither CDKN1C mRNA nor protein expression level was correlated to the placenta weight (mRNA:SGA group,r=0.119,P=0.540;AGA group,r=-0.069,P=0.722;protein:SGA group,r=0.126,P=0.515;AGA group,r=-0.247,P=0.196).Conclusions The expressions of CDKN1C mRNA and protein may be related to birth weight of term SGA neonates,especially in male infants.