Consideration of Ethical Protection in Drug Clinical Trials for Rare Diseases in Children / 中国医学伦理学

Children with rare disease belong to a vulnerable group. When China’s current medical security system cannot provide comprehensive health care, they not only face physical and mental torture, but also have a higher risk of children participating in clinical trials than adults. So, adequate protection of children’s safety and rights is the key to ethical review. This paper analyzed the current status of drugs clinical trials for rare disease in children, including trial difficulties and guarantee system; explained the ethical principles that should be followed in clinical trials, such as the principle of informed consent and the principle of no harm; and discussed the path of protecting children’s safety and rights, so as to raise awareness and attention of the importance of ethical review of clinical trials.

Transfer learning enhanced graph neural network for aldehyde oxidase metabolism prediction and its experimental application

Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from 13C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

BFGF attenuates aortic valvular interstitial cell calcification by inhibiting endoplasmic reticulum stress-mediated apoptosis.

The potential protective effect of basic fibroblast growth factor (BFGF) on the cardiovascular system has been proposed previously, however, its effect on calcific aortic valve disease (CAVD) and underlying mechanisms have not been elucidated. The valvular interstitial cell (VIC) were isolated from porcine aortic valve leaflets. To investigate the effect of BFGF on osteogenic differentiation of VIC, the osteogenic induced medium (OIM) and BFGF were added. The protein expression level was detected by Western blot, and apoptosis was determined by flow cytometry. The effect of BFGF on CAVD process in vivo was assessed by a rat CAVD model, which was identified by echocardiography and Alizarin red staining. The expression level of BFGF in the aortic valve and serum were significantly upregulated in CAVD patients compared to control group. In addition, exogenous BFGF injection attenuates CAVD process in vivo. The protein markers of osteogenic differentiation, endoplasmic reticulum stress (ERS), and apoptosis were significantly upregulated by culture with OIM. On the contrary, the aforementioned proteins were suppressed after adding 100 ng/mL of BFGF. Inhibition of PI3K/Akt and ERK1/2 pathways by specific inhibitors abolished the protective effect of BFGF. In conclusion, BFGF could alleviate the VIC calcification by inhibiting ERS-mediated apoptosis, which is partly regulated by activation of the PI3K/Akt and ERK1/2 signaling pathways. BFGF may provide a potential avenue for CAVD therapy.

CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules / 中国肺癌杂志

BACKGROUND@#Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules.@*METHODS@#122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed.@*RESULTS@#Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples.@*CONCLUSIONS@#CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.

Summary of best evidence for exercise rehabilitation for stroke / 中国实用护理杂志

Objective:To summarize the relevant evidence of motor rehabilitation of stroke at home and abroad, so as to provide reference for medical staff to carry out motor rehabilitation.Methods:The related evidence on exercise management for patients with stroke in BMJ Best practice, UpToDate, Joanna Briggs Institute (JBI) Evidence-Based Health Care Center Database, National Guideline, American Heart Association/American Stroke Association, European Stroke Organization, National Institute for Health and Care Excellence, Registered Nurses Association of Ontario, Canadian Medical Association, American Association of Critical Care Nurses, National Stroke Foundation, Chinese Stroke Association, Medlive, Cochrane library, PubMed, Web of Science, Embase, OVID, Medline, China National Knowledge Infrastructure, Wanfang, VIP, SinoMed were searched by computer. The retrieval time limit was from 2012 to June 30, 2022. Two to four investigators independently assessed the quality of the included article, and extracted and summarized the evidence that met the quality standards.Results:A total of 22 articles were included, including 5 guidelines, 2 summary of evidence, 2 expert consensus, and 13 systematic evaluations. A total of 42 pieces of evidence related to exercise rehabilitation were extracted and integrated, including 11 aspects such as multidisciplinary teams, exercise goals, exercise timing, exercise evaluation, exercise venue, exercise style, exercise intensity, exercise time and frequency, safety monitoring, exercise behavior maintenance, and health education.Conclusions:The best evidence summarized in this study can provide a reference for clinical medical staff to implement exercise rehabilitation, but in clinical practice, it is necessary to select and apply evidence in a targeted manner in combination with specific circumstances, so as to improve the safety and effect of exercise rehabilitation.

Altered Caffeine Metabolism Is Associated With Recurrent Hypoglycemia in Type 2 Diabetes Mellitus: A UPLC-MS-Based Untargeted Metabolomics Study.

Background: Recurrent hypoglycemia (RH) is well known to impair awareness of hypoglycemia and increase the risk of severe hypoglycemia; the underlying mechanism requires further understanding. We aimed to investigate the metabolic characteristic profile for RH in type 2 diabetes mellitus (T2DM) patients and explore the potential metabolic mechanism and prevention strategies. Methods: We screened 553 community-based T2DM patients. T2DM with RH (DH group, n=40) and T2DM without hypoglycemia (DC group, n=40) were assigned in the case-control study, matched by propensity score matching. Non-targeted, global metabolite profiling was conducted using ultra-high performance liquid chromatography-mass spectrometry. Principal component analysis and supervised projections to latent structures-discriminant analysis were constructed to evaluate the potential biomarkers. Metabolites with a fold change of >2.0 or <0.5, a t-test q-value <0.05, and variable importance in projection value of >1 were identified as significantly differential metabolites. MetaboAnalyst was performed to analyze the related metabolic pathways. Results: We identified 12 significantly distinct metabolites as potential biomarkers of RH, which were enriched in five pathways; the caffeine metabolic pathway was the most dominant related one. Caffeine and its main downstream metabolites (theophylline and paraxanthine, all q <0.05) were significantly lower during RH. The combination of these metabolites can serve as a reliable predictor biomarker for RH (area under the curve = 0.88). Regarding lipid metabolism, triglyceride was upregulated (P=0.003) and the O-Acylcarnitine was downregulated (q < 0.001). Besides, RH was accompanied by lower phenylalanine (q=0.003) and higher cortisone (q=0.005) levels. Conclusions: RH in T2DM is accompanied by caffeine, lipolysis, phenylalanine, and cortisone metabolism abnormalities. Caffeine might be a reliable candidate biomarker and potential prevention strategy for RH, but further validation studies are needed. Clinical Trial Registry: Chi CTR 1900026361, 2019-10-3.

Influencing factors of coronary artery lesions in children with Kawasaki disease / 西安交通大学学报(医学版)

【Objective】 To study the influencing factors of blood source indicators related to coronary artery lesions in children with Kawasaki disease (KD). 【Methods】 Clinical data of children diagnosed with KD admitted to our hospital from January 1, 2015 to December 31, 2019 were retrospectively analyzed. Baseline data comparison and multivariate Logistic regression analysis were used to compare the differences in blood source indicators between the coronary artery lesion (CAL) group and the non-coronary artery lesion (nCAL) group, and the receiver operating characteristic (ROC) curve was drawn. 【Results】 There were significant differences in sex, erythrocyte sedimentation rate (ESR), lymphocyte count (L#) and red blood cell distribution width (RDW) between the CAL group and the nCAL group (P<0.05). Male, lower ESR, lower L#, and higher RDW were independent risk factors for CAL. OR values and their 95% confidence intervals (95% CI) were 0.279 (0.117, 0.669), 0.973 (0.955, 0.992), 0.675 (0.513, 0.889), and 2.433 (1.313, 4.506), respectively. The sensitivity and specificity of RDW for predicting CAL were 37.3% and 86.4%, the best cutoff value was 13.45%, the area under curve (AUC) was 0.616, and 95% CI was (0.514, 0.718) (P<0.05). ESR and L# had no predictive value for CAL. 【Conclusion】 Blood source indicators of children with Kawasaki disease, including blood routine and inflammatory indicators, especially RDW, have certain predictive value for coronary artery lesions. They can be combined with echocardiography to evaluate disease progression.

Exploration and practice of constructing a risk-based quality management model for clinical trials / 中华医学科研管理杂志

Objective:To conduct a quantitative and qualitative analysis of the issues found in quality management, establish a risk-based whole-process quality management model, and improve the quality of clinical trials.Methods:Based on the risk-based quality management theory, the issues found in the quality control of drug clinical trials in Beijing Cancer Hospital in 2020 were structured and classified by severity (mild to moderate to severe) and 10 categories, and the risk matrix was graded by a semi-quantitative method. Targeted quality control strategies for different levels of risk were carried out according to visual analysis of the informative quality analysis platform. Chi-square tests of the severity of quality control issues in our hospital in 2020 and 2021 and non-parametric tests of the number of issues per capita in each category were used to evaluate the effectiveness of the management model.Results:A risk matrix was established according to the severity and frequency of the issues found in the quality control in 2020. The issues with severe risks were categorized as protocol compliance and serious adverse events, and categories with moderate risks included informed consent, biological sample related, original records, and investigator folders. After using visual analysis and adopting the risk-based quality control strategy, the proportion of severe issues found in quality control in our hospital in 2021 was 0.92%, lower than that of 1.39% in 2020, and the difference was statistically significant. The average number of issues detected per capita in each category for each trial in 2021 was lower than that in 2020 with a statistical difference, indicating that the management model was effective.Conclusions:Using information technology to adopt risk-based quality management is helpful to improve the quality of hospital clinical trials.

Expression of MAD2L1 in Lung Adenocarcinoma and Its Effect on Immune Microenvironment / 肿瘤防治研究

Objective To investigate the expression of MAD2L1 in lung adenocarcinoma and its effect on the prognosis and immune microenvironment of patients. Methods The difference of MAD2L1 expression in lung adenocarcinoma tissue and normal lung tissue was analyzed by TCGA and GEO database. Survival analysis was carried out to evaluate the prognostic significance of MAD2L1 gene expression in lung adenocarcinoma patients. StarBase database was used to construct miRNA-MAD2L1 regulatory network of lung adenocarcinoma. The relation between the expression of MAD2L1 and immune cell infiltration in lung adenocarcinoma was analyzed by TIMER database. Results The expression of MAD2L1 was up-regulated in lung adenocarcinoma, and the high expression of MAD2L1 was significantly correlated with pathological stage and lymph node metastasis of lung adenocarcinoma. The patients with high expression of MAD2L1 had a poor prognosis. miR-101-3p/MAD2L1 axis was identified as the most potential upstream regulation pathway of MAD2L1 in lung adenocarcinoma. The expression level of MAD2L1 was significantly correlated with tumor immune cell infiltration and immune checkpoint expression. Conclusions MAD2L1 is highly expressed in lung adenocarcinoma, which is related to poor prognosis and tumor immune infiltration. MAD2L1 can be used as a potential target for the treatment of lung adenocarcinoma.

Drug target inference by mining transcriptional data using a novel graph convolutional network framework

A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or off-target effects. Recently, the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology. Here, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, and the biological networks under different experiment conditions further complicate the situation, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. On a benchmark set and a large time-split validation dataset, the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map. Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound, or reversely, in finding novel inhibitors of a given target of interest.

Study on the contamination level and dietary exposure of 9,10-anthraquinone in different types of teas in Wuhan / 公共卫生与预防医学

Objective To investigate the pollution level of 9,10-anthraquinone in teas sold in Wuhan, and to assess the dietary exposure of 9,10-anthraquinone ingested through tea. Methods The content of 9,10-anthraquinone in teas collected from local tea markets in Wuhan was analyzed by GC-MS/MS. Results 9,10-anthraquinone was detected in all 36 tea samples with a concentration ranging from 0.0080 mg/kg to 0.137 mg/kg. The standard limit for 9,10-anthraquinone has not yet been set in China. Referring to EU standards, the total over-standard rate was 86.11% (31/36). Generally, the concentration of residual 9,10-anthraquinone was higher in highly fermented teas. The highest average concentration of residual 9,10-anthraquinone was found in fully/post-fermented tea (0.0762 mg/kg), and the over-standard rate was 100%. The second highest was in semi-fermented tea (0.0452 mg/kg), and the over-standard rate was 86.7%. The concentration of 9,10-anthraquinone in non-fermented tea was 0.0262 mg/kg, and the over-standard rate was 42.9%. According to people’s tea-drinking habits, tea samples were brewed with boiling water（1:50）for 5 minutes, and the concentration of 9,10-anthraquinone in tea soup was 0.0004 mg/kg～0.01 mg/kg, with an average leaching rate of 7.2%. The average daily intake exposure of tea for an adult was 0.0551μg/kg bw/day. Conclusion There was a certain degree of 9,10-anthraquinone pollution in the teas sold in Wuhan, and the rate exceeding the standard was high. Since the acceptable daily intake (ADI) for 9,10-anthraquinone has not been established, it is impossible to assess the health risks of 9,10-anthraquinone ingested through tea.

Chronic inflammatory response syndrome in the elderly / 中华老年医学杂志

Chronic inflammatory response syndrome(CIRS)is a chronic, low-grade, systemic inflammatory response, resulting from sustained long-term stimulation of the innate immune system.CIRS is not only associated with certain chronic diseases, but also associated with aging, the development and progression of a variety of diseases in the elderly, and functional decline.Additionally, it is closely related to adverse clinical outcomes and is not uncommon in the elderly.Here we review the characteristics of CIRS and their clinical implications and consider whether CIRS can be classified as a geriatric syndrome, in order to identify new targets for the prevention and treatment of diseases and functional decline in the elderly.

Research progress of mTOR in digestive system neoplasms / 中国医师杂志

Mammalian target of rapamycin (mTOR) is involved in a variety of cellular signaling pathways, which is related to cell growth, proliferation, autophagy, apoptosis and cell cycle progression.mTOR signaling pathway is usually activated in tumors and is closely related to the occurrence, progression and metabolism of tumors.Therefore, mTOR signaling pathway is a hot spot in anti-tumor therapy research.In recent years, with the research of the mechanism of mTOR signaling pathway in digestive system tumors and the exploration of inhibitors, new ideas have been provided for clinical diagnosis and treatment, prognosis assessment and targeted drug development.

A survey and an intervention study on Chinese medical students' willingness to pursue a career in geriatrics / 中华老年医学杂志

Objective:To explore the attitudes of Chinese medical students toward the elderly and their willingness to practice in geriatrics, and to investigate the influence of geriatrics education on their attitudes.Methods:Medical students studying diagnostics in four medical universities were enrolled in a cross-sectional survey and, for the intervention study, graduate trainees from non-geriatrics specialties taking a geriatrics course were interviewed before and after the course.An electronic questionnaire was used to collect general information, the experience of interacting with the elderly, attitudes towards the elderly and the willingness to develop careers in geriatric medicine.Changes in attitudes towards the elderly and their willingness to practice in geriatrics before and after the 40-hour geriatric medicine course were compared.Results:A total of 648 medical students completed the cross-sectional survey, with the highest score in compassion for the elderly(3.54±0.54)and the lowest score for medical services for elderly patients(3.36±0.78). Only 2.2%(14/648)of the students showed strong interest in geriatric medicine.The results of the intervention from 42 graduate trainees showed that the average scores of revised Geriatric Attitude Scale(r-GAS)were 3.80±0.43 and 3.92±0.40 before and after the course, respectively, and the difference was statistically significant( t=2.148, P=0.038). At the end of the course, 7 trainees(16.7%, 7/42)showed great interest in geriatrics, significantly different from 2 trainees(4.8%, 2/42)before the course( χ2=8.211, P=0.025). Conclusions:Chinese medical students show a serious lack of interest in geriatrics, and geriatrics education can improve their attitudes towards the elderly and their willingness to work in geriatrics.With the rapid population aging in China, it is urgent to strengthen the education of geriatric medicine.

Research progress of exercise rehabilitation in women with perimenopausal syndrom / 中国实用护理杂志

Perimenopausal syndrome is a common uncomfortable symptom in women during the perimenopausal period, with a high incidence, a long duration, and adverse effects on physical and psychological, patients bear a heavy burden of symptoms, and increase the risk of adverse events in the elderly stage, increase the social medical burden. With the development of sports rehabilitation research, more and more attention has been paid to the effect of exercise on human health. This paper reviews the studies on exercise rehabilitation in women with perimenopausal syndrome, including exercise forms, exercise intensity, exercise time and exercise effect, in order to provide basis for the relevant research and practice.

Correlation between hypophosphatemia and the severity of Corona Virus Disease 2019 patients

ObjectiveRetrospectively analyze the clinical data of Corona Virus Disease 2019 (COVID-19) patients and explore the value of serum phosphorus level in evaluating the severity and prognosis of the disease. MethodsCOVID-19 patients transferred from the first emergency ward of Taiyuan fourth peoples Hospital from February 8 to March 3, 2020 were enrolled. The information of general conditions, clinical manifestations, laboratory indexes, nucleic acid detection and treatment were collected. The changes of blood phosphorus level and absolute value of lymphocytes in ordinary and severe/critical patients were recorded and compared. ResultsA total of 32 patients with COVID-19 were collected, including 12 cases of common type and 20 cases of severe/critical type. Before treatment, the serum phosphorus levels of the two groups were significantly lower than the normal level, and the serum phosphorus levels of the severe/critical patients were lower than those of the common type patients (t = 2.767, P < 0.010). After treatment, the serum phosphorus levels of the two groups reached normal, and there was no significant difference between the two groups (t = 0.231, P >0.819). The level of lymphocytes in severe/critical patients was lower than that in normal patients (t = 4.636, P < 0.001) before treatment. After treatment, the absolute value of lymphocytes in the two groups reached normal, and there was no significant difference between the two groups (t=1.208,P=0.237). There was a positive correlation between lymphocytes and serum phosphorus, and the correlation coefficient was 0.479. Conclusionhypophosphatemia is related to the severity of COVID-19, and strengthening the monitoring of serum phosphorus level of COVID-19s severe/critical patients and correcting hypophosphatemia in time are of significance to improve the prognosis.

Analysis of the Rules of Pulmonary Nodule Prescriptions Based on TCMISS / 中国药房

OBJECTIVE：To provide reference for improving TCM treatment of pulmonary nodule. METHODS ：The experience of famous TCM doctors in the TCM treatment of pulmonary nodule was searched by computer ，the formulations of the cases were sorted out ，and the data were recorded into the TCMISS V 2.5 for data analysis ，and the medicine frequency was counted. Apriori algorithm and association rules were used for statistical analysis of core combination of formulations （support degree was 16，confidence degree was 0.65）. Inner core combination and new combination were extracted according to the entropy clustering method of complex system （correlation was 6，penalty was 2）. RESULTS ：A total of 25 literatures were input ，including 64 formulations in total ，166 medicinal materials. For the prescriptions of pulmonary nodule ，the frequency of single ingredient from high to low was Bolbostemma paniculatum ，Glycyrrhiza uralensis ，Astragalus membranaceus ，Prunella vulgaris ，Ostrea gigas，Angelica sinensis ，Pinellia ternate ，Ligusticum chuanxiong ，Mori Corlex ，etc. The main compatibility of the drug model is to invigorate Qi ，dissipate phlegm ，invigorate Qi and activate blood circulation ，and promote Qi and softness ，such as “G. uralensis，B. paniculatum ”“A. membranaceus ，B. paniculatum ”“A. membranaceus ，G. uralensis ”，etc；10 core combinations of the drug were found out ， such as Begonia fimbristipula-Rhodiola rosea-Bupleurum Chinense ， Cervus elaphus Clematis chinensis-Buffalo Horn，etc. There were 5 new prescriptions ，i.e. B. fimbristipula-R. rosea-B. chinense-Setaria italic ，C. elaphus-C. chinensis-Buffalo Horn-French chalk ，A. sinensis-L. chuanxiong-Morus alba- Mori Corlex -P. vulgaris-Ganoderma lucidum ，Hedyotis diffusa-Prunus persica-Trichosanthes kirilowii-Achyranthes bidentata-Eupolyphaga sinensis- Cinnamomi Ramulus ，A. bidentata-E. sinensis-Ephedra sinica-Curcuma aromatica-Curcuma longa-Concretio silicea . CONCLUSIONS ：Most modern doctors believe that the interaction of phlegm and blood stasis is the main pathogenesis of pulmonary nodule ，and the treatment is mainly based on the treatment of lung ，spleen，liver and kidney ，focus on the elimination of symptoms and phlegm ，the elimination of blood stasis and the soft and hard treatment ，pay attention to the weak body of the patient. TCM treatment of pulmonary nodule has a good prospect.

Discussion on the management mode of real-time reimbursement of testing expense in clinical trials / 中华医学科研管理杂志

Objective:To explore the management mode of the real-time reimbursement of testing expenses in clinical trials, dealing with the possible disadvantages of manual reimbursement and improving work efficiency.Methods:Based on hospital information system, the GCP center integrates the clinical trial information system, optimizes the trial reimbursement process, and explores a unique " clinic-GCP-finance" streamlined clinical trial real-time settlement management model.Results:This management mode of real-time reimbursement of testing expenses has been adopted for 3 years. This management model enables human subjects to complete the reduction or exemption of clinical trial-related medical testing expenses before making the payments, which is also highly praised by both investigators and subjects.It complied with informatization and technology development in the era of big data, realized full process dynamic supervision over clinical trial lab testing expenses and avoided management delay. It also had advantages in simplifying reimbursement process, reducing work load and mistakes, complying with inspection and improving trial quality.Conclusions:Clinical trial real-time reimbursement management mode of testing expenses works better in compliance with GCP, safeguards the rights and interest of human subject, and can provide a certain reference for other GCP centers.

On the current situation of the knowledge-attitude-practice of clinical scientific research ability of pediatric residents in standardized residency training / 中华医学教育探索杂志

Objective:To understand the clinical research knowledge, attitude and practice of pediatrics residents in standardized residency training, and to provide scientific basis for improving their capability of clinical medical scientific research.Methods:A self-complied questionnaire survey including demographic information, knowledge and attitudes toward capability of medical scientific research as well as personal interview was conducted in 22 pediatric residents during the standardized residency training from April to July, 2017. Data were analyzed by (mean±standard deviation) and percentage for description, and qualitative data were analyzed by classification and induction. SPSS 18.0 was used to analyze the data.Results:Firstly, the total score of basic knowledge in clinical scientific research was (54.14±23.06), with the scores between 31 and 60 being the most. Secondly, all these residents believed that capability of clinical medical scientific research was very important for them and clinical research training was necessary for them during the standardized residency training. Thirdly, the residents had the scientific research practices but no article published during the standardized residency training. Fourthly, the residents hoped to improve their capability of clinical scientific research by various means during the training.Conclusion:It is indicated that basic knowledge on capability of clinical medical research is still insufficient in standardized residency training of pediatrics residents, so relevant measures should be taken to cultivate their capability of clinical scientific research.

Expressions of transforming growth factor β 1 and dimethylarginine dimethylaminohydrolase 2 in early-stage lung adenocarcinoma and their clinical significances / 肿瘤研究与临床

Objective:To investigate the expressions and significances of transforming growth factor β 1 (TGF-β 1) and dimethylarginine dimethylaminohydrolase 2 (DDAH2) in different stages of early-stage lung adenocarcinoma, and to provide basis for accurate pathological diagnosis of lung adenocarcinoma. Methods:Sixty-two surgical specimens from patients with early-stage lung adenocarcinoma in Shanxi Bethune Hospital from January 2012 to June 2019 were selected. Most of the specimens contained more than one pathological type. According to the pathological types, they were divided into three groups: 18 cases of atypical adenomatous hyperplasia (AAH), 60 cases of adenocarcinoma in situ (AIS), and 55 cases of invasive carcinoma (CA) component in minimally invasive adenocarcinoma (MIA) and lepidic predominant adenocarcinoma (LPA), and the wall attached growth patterns were selected as control group. Immunohistochemistry was used to detect the expressions of TGF-β 1 and DDAH2 proteins in different pathological types of lesions and control tissues, and the correlation among them was analyzed. Results:TGF-β 1 and DDAH2 proteins were expressed in normal lung tissue epithelial cells, and the positive rates were high [46.8% (29/62) and 98.4% (61/62)]. The positive rates of TGF-β 1 and DDAH2 proteins in epithelial cells of AAH, AIS and CA increased gradually, the positive rate of TGF-β 1 protein was 16.7% (3/18), 31.7% (19/60) and 70.9% (39/55), the positive rate of DDAH2 protein was 66.6% (12/18), 81.7% (49/60) and 90.1% (49/55), and the differences of positive rates among different pathological types were statistically significant (all P < 0.01). The positive rates of TGF-β 1 and DDAH2 protein in interstitial fibroblasts of normal lung tissue, AAH, AIS and CA increased gradually, the positive rate of TGF-β 1 protein was 11.3% (7/62), 61.1% (11/18), 72.3% (44/60), and 83.6% (46/55), the positive rate of DDAH2 protein was 0 (0/62), 22.2% (4/18), 65.0% (39/60), and 98.2% (54/55), and the differences of positive rates among different pathological types were statistically significant (all P < 0.01). In lung adenocarcinoma tissues, there was a positive correlation between the expression of TGF-β 1 in epithelial cells and the expression of DDAH2 in interstitial fibroblasts ( r = 0.221, P = 0.011). Conclusions:The expression trend of TGF-β 1 and DDAH2 proteins in different pathological types of early-stage lung adenocarcinoma lesions may relate to the degree of lesions. The combined detection of TGF-β 1 and DDAH2 proteins is expected to be a biomarker for the auxiliary diagnosis of early-stage lung adenocarcinoma with different pathological types.