Objective To synthesize N-(4-fluorophenyl)-N-(4-phenoxyphenyl) cyclopropane-1,1-dicarboxamide (NFNPDB) as small molecular c-Met kinase inhibitor analogue.Methods N-( 4-fluorophenyl )-N-( 4-phenoxyphenyl ) cyclopropane-1, 1-dicarboxamide was synthesized by nucleophilicsubstitution, amidation, etherification, reduction and condensation from diethyl malonate.Results The total yield of target compound was 3.79%, its structure was confirmed by 1 H-NMR.Conclusion The synthesis method of NFNPDB in our research can be easily operated with lost cost and short direction, which lays the foundation for designing the synthetic process of newly small molecular c-Met kinase inhibitor.

Objective To design and synthesize compounds with protein tyrosine kinase(PTK)inhibitory activity with L029 as the lead compound. Methods L029 derivatives were designed and synthesized from L029 by reduction and/or substitution with the 3-dimethylamino-1-propyl,methyl acetate,methyl propionate in its active H and other sites. PTK activity was measured by enzyme-linked immunosorbent assay(ELISA). The inhibitory rate was calculated to screen out the compounds with PTK inhibitory activity. Re-sults Five target compounds were synthesized and their structures were confirmed by 1H NMR and MS. Three compounds T2,T3 and T5 were screened out with strong PTK inhibitory activity. Conclusion The synthetic routes of the target compounds are simple with mild reaction condition,and 3 compounds show strong inhibitory activity by ELISA. These results can provide reference for the further design and synthesis of this kind of molecules.

Objective To design and synthesize novel 2-indolone derivatives as the c-Met kinase inhibitors. Methods With c-Met kinase inhibitor SU11274 as lead compound,a series of 2-indolone derivatives were designed according to the concept of bioiso-sterism. Then the target compounds(10a-10r)were synthesized from 2-indolone through 5-chlorosulfonation with chlorosulfonic acid, sulfonamidation with intermediate 3,condensation with 6a-6h,7a-7h and 4a-4b,respectively. Their inhibitory activity against c-Met and proliferation of MCF-7 cells were evaluated. Results and Conclusion The designed compounds were successfully prepared and their structures were confirmed by 1H NMR and ESI-MS. Some compounds had certain inhibitory activity against c-Met and prolif-eration of MCF-7 cells. An initial structure-activity relationship analysis of these compounds was performed to provide useful informa-tion for further optimization of their structures.

Dyslipidemia is one of the most common complications of primary biliary cholangitis (PBC). This article reviews the latest research on lipid profile, the risk of cardiovascular diseases, and treatment of PBC with hyperlipidemia. Different from other liver diseases, PBC with hyperlipidemia has a unique lipid profile, which changes dynamically with disease progression. It is generally not considered that there are increased risks of atherosclerosis and cardiovascular disease. For those who have indications for treatment, statins are recommended as the first choice. In the future, more in-depth systematic studies are needed to clarify its diagnosis, treatment, and management processes.

Objective:To translate the Efficacy of Self-Efficacy for Managing Symptoms (SEMSX) based on the Patient-Reported Outcomes Measurement Information System (PROMIS) into Chinese, and to test the reliability and validity of the scale among Chinese patients with nasopharyngeal carcinoma.Methods:The English version of PROMIS-SEMSX was translated into Chinese according to the FACIT translation method. The reliability and validity of the scale were evaluated. From January to April in 2021, the convenient sampling method was adopted to select 205 patients with nasopharyngeal cancer in Zhejiang Cancer Hospital for investigation.Results:The Chinese version of PROMIS-SEMSX scale consisted of 28 items in 4 dimensions, which were consistent with confidence level(with 7 items), symptom management(with 5 items), the impact of symptoms on life(9 items), seeking and understanding support(7 items). The calibration correlation validity was 0.935. The total Cronbach α coefficient of the scale was 0.966, and the half-reliability of the total scale was 0.891. The Cronbach α coefficient of each dimension was 0.910-0.938, and the total retest reliability coefficient of the scale was 0.757.Conclusions:The Chinese version of PROMIS-SEMSX has good reliability and validity in patients with nasopharyngeal carcinoma, and provides a new tool for patients with nasopharyngeal carcinoma to evaluating self-efficacy symptom management.

Objective:To explore the status quo of symptom management self-efficacy based on patient reported outcomes of nasopharyngeal carcinoma patients and analyze its related factors.Methods:From January to April 2021, 230 patients with nasopharyngeal carcinoma who were treated in Zhejiang Cancer Hospital were selected as the study subject by convenient sampling. The General Information Questionnaire and Patient-Reported Outcome Measurement Information System-Self-Efficacy for Managing Symptoms (PROMIS-SEMSX) were used to investigate. Single factor analysis and multiple linear regression analysis were used to explore the influencing factors of symptom management self-efficacy in patients with nasopharyngeal carcinoma.Results:A total of 230 questionnaires were distributed, 220 were recovered, and 205 were valid. The score of symptom management self-efficacy of patients with nasopharyngeal carcinoma was (97.74±20.00) , which was above the middle level, and the lowest score dimension was confidence, which was (23.52±5.91) . Multiple linear regression showed that gender, education level, medical expense payment method, economic level, tumor stage, course of disease, tumor recurrence and metastasis were the influencing factors of symptom management self-efficacy of nasopharyngeal carcinoma patients ( P<0.05) . A total of 41.5% of the total variation was explained. Conclusions:The self-efficacy of symptom management in patients with nasopharyngeal carcinoma needs to be improved. The medical and nursing staff should focus on the patients with low educational level, heavy economic burden, late tumor, recurrence and metastasis, and focus on providing specific health guidance to alleviate their discomfort symptoms during treatment, and improve their self-efficacy of symptom management.

Objective To understand the situation of college students' knowledge, attitude and practice (KAP) of innovation and entrepreneurship activities and analyze their influencing factors, in order to provide a scientific basis for further promotion of innovation and entrepreneurship activities. Methods A self-administered questionnaire survey using cluster sampling method was conducted among 850 undergraduates in a medical university in May, 2018. The demographic characteristics and questions pertaining to the KAP of innovation and entrepreneurship activities were collected, The weighted scores of KAP were calculated using the Delphi method. Chi-square test, multivariate logistic regression and linear regression analysis were used to analyze the data. Results A total of 850 questionnaires were sent out and 800 valid questionnaires were collected. The average scores and pass rates for the knowledge, attitude and practice of the 800 college students were (0.54 ±0.14), 38.1％; (0.56 ±0.23), 51.5％; and (0.37 ±0.19), 12.6％, respectively. Knowledge: the pass rate for the concepts related to innovation and entrepreneurship was 70.5％, and the pass rate for the policies related to innovation and entrepreneurship was 17.2％. The pass rate of senior students and excellent students were higher than those of junior students and students of lower academic competence (P=0.000, P=0.004). Attitudes: the pass rate for attitude towards the relationship between innovation and entrepreneurship and personal development was 63.6％, the pass rate for attitudes towards participation in innovation and entrepreneurship was 49.8％, and the pass rate for attitudes towards the school continuing to carry out innovation and entrepreneurship related activities was 23.8％. Practice:the pass rates for participation in scientific research and academic activities and social practice , voluntary cultivation of innovation ability and self-employment were 8.5％, 62.9％, 11.9％and 27.3％, respectively. The pass rate of senior grades was higher than that of junior grades (P=0.001). Scores for knowledge and those of attitude are positively correlated. Scores for practice and those of knowledge and attitude are positively correlated. Conclusion The higher pass rates for medical college students' attitude toward innovation and entrepreneurship activities as compared to those for knowledge and practice indicates high eagerness toward participation in innovation and entrepreneurship activities; a high rate knowledge is conducive to the cultivation of attitudes and the improvement of participation in activities . Therefore , it is necessary to strengthen the efforts in carrying out innovation and entrepreneurship activities , improve publicity and education, and promote the awareness-raising of innovation and entrepreneurship.

Objective To analyze the current status and trends of chronic kidney disease (CKD) burden in China from the global perspective, and to provide reference for the prevention and control of CKD in China. Methods The incidence, prevalence, mortality and disability adjusted life year (DALY) rate of China and other regions were retrieved from GBD 2019. Comparative analyses were carried out to reflect the burden of CKD. Results In 2019, the incidence and the prevalence in females were higher than those in males, while the mortality and the DALY rates in females were lower than those in males. There were obvious distinctions in different age groups and people over 65 years old had a higher CKD burden. The burden of CKD mainly came from hypertensive nephropathy and type 2 diabetic nephropathy. From 1990 to 2019, the DALY rate of CKD in China showed an overall upward trend. After eliminating the differences in age composition, the standardized DALY rate of CKD in China was higher than that in Japan, Korea and Ukraine although lower than the global. The main influencing factors of the burden of CKD were metabolic factors. Conclusion The burden of CKD in China is continuously rising. It is still necessary to pay attention to the three-level prevention and control, and focus on the key people groups and high-risk factors to further reduce the burden of CKD in China.

Objective: To investigate the role of human papillomavirus (HPV) 16 early genes E2 and E6 and heterogeneous nuclear ribonucleoprotein (hnRNP) E2 and their interaction effects in the progression of the cervical cancer. Methods: Women with normal cervix (NC), low cervical intraepithelial neoplasia (CIN Ⅰ) and high cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ) from the cervical lesions cohort in Jiexiu County of Shanxi Province from June 2014 to September 2014, and patients with cervical squamous cell carcinoma (SCC) treated at the Second Hospital of Shanxi Medical University in the same period were enrolled in this study. There were 257 participants, about 67 NC cases (26.07%), 69 CIN Ⅰ cases (26.85%), 68 CIN Ⅱ/Ⅲ cases (26.46%), and 53 SCC cases (20.62%), respectively. The information of demographic characteristics, life health habits and cervical lesions were collected by using the structured questionnaire. Cervical exfoliated cells and cervical biopsy tissues were collected to detect the infection of HPV16 and the protein expression levels of hnRNP E2, HPV16 E2 and E6. According to the median-value of the protein expression levels of hnRNP E2, HPV16 E2 and E6 and E2/E6 ratio in the NC group, the study participants were divided into the high and low expression groups/ratio groups. The multivariate logistic regression model was used to analyze the correlation between HPV16 early gene E2 and E6, hnRNP E2 and cervical cancer. The interaction effect was analyzed by using the generalized multifactor dimensionality reduction (GMDR) model. Results: The ages of NC, CIN Ⅰ, CIN Ⅱ/Ⅲ and SCC groups were (47.00±9.07), (47.64±7.35), (46.37±8.67) and (51.26±8.03) years old, respectively. The multivariate logistic regression model analysis showed that the HPV16 E2 low expression, E6 high expression and E2/E6 low ratio could increase the risk of CIN Ⅱ/Ⅲ, about OR (95%CI) values 11.11 (1.63-75.56), 8.00 (1.28-50.04), and 9.75 (1.22-77.72), respectively and SCC, about OR (95%CI) values 14.22 (2.11-95.88), 10.33 (1.67-64.00), and 12.38 (1.56-97.91), respectively. The hnRNP E2 low expression could increase the risk of CIN Ⅱ/Ⅲ and SCC, about OR (95%CI) values 3.35 (1.39-8.10) and 5.53 (1.54-19.88). The result of GMDR showed that there were interaction effects of the hnRNP E2 low expression, HPV16 E2 low expression and HPV16 E6 high expression in both CIN Ⅱ/Ⅲ and SCC groups. Conclusion The HPV16 E2 low expression, HPV16 E6 high expression and hnRNP E2 low expression could increase the risk of high-grade cervical intraepithelial neoplasia and cervical cancer, and they might have an important interaction effect in the progression of the cervical cancer.

Objective:To explore the value of tacrolimus blood concentration and other related indexes in evaluating early postoperative infection in patients with liver transplantation.Methods:Patients with complete medical records who underwent liver transplantation in the First Affiliated Hospital of Nanjing Medical University from January 2014 to December 2019 were screened. Cohort study was used, and demographic data, laboratory test results, tacrolimus blood concentration and other data of patients with liver transplantation were collected. All patients with postoperative infection were divided into four groups, inculding two to four weeks, five to 12 weeks, 13 to 52 weeks and >52 weeks groups, and uninfected patients in each group were matched 1∶1 according to age ± 3 years old. Independent sample t test and rank sum test were used to analyze the differences in clinical data between postoperative infected and uninfected patients with liver transplantation patients. Logistic regression analysis was used to explore the influencing factors of infection in the early postoperative period (two to four weeks after operation). The relative safe value of tacrolimus blood concentration in the early postoperative period was evaluated by receiver operating characteristic curve. Results:A total of 150 patients with infection after liver transplantation were included, including 65 patients in the two to four weeks group, 31 patients in the five to 12 weeks group, 27 patients in the 13 to 52 weeks group, and 27 patients in the >52 weeks group. There were 52, 30, 32, and 39 uninfected patients in the four groups, respectively. There were 247 males (81.52%) in 303 patients with liver transplantation, and the age ranged from 10 to 78 years old. Hepatitis B cirrhosis and hepatocellular carcinoma were the main primary diseases, accounting for 41.91%(127/303) and 47.52%(144/303), respectively. The tacrolimus blood concentration and alanine aminotransferase in patients with infection in the two to four weeks group were (11.46±4.94) μg/L and 118.20(38.80, 215.80) U/L, respectively, which were both higher than those in the uninfected group ((7.12±2.33) μg/L and 39.40(23.40, 142.70) U/L, respectively). The differences were both statistically significant ( t=6.26, Z=2.66, respectively, both P<0.05). Sputum sources accounted for the largest number of samples, accounting for 61.6%(98/159). A total of 174 pathogens were isolated, of which gram-negative bacteria (55.2%(96/174)) were the majority, mainly Klebsiella pneumoniae (20.1%(35/174)) and Acinetobacter baumannii (13.8%(24/174)). Multivariate analysis showed that tacrolimus blood concentration (odds ratio ( OR)=1.634, 95% confidence interval ( CI) 1.298 to 2.058, P=0.001) was a risk factor for infection at two to four weeks after liver transplantation, while lymphocyte count ( OR=0.165, 95% CI 0.057 to 0.474, P=0.010) was a protective factor. The area under the curve of tacrolimus blood concentration in evaluating the infection at two to four weeks after liver transplantation was 0.817. The cut-off value was 8.7 μg /L ( P<0.05), with the sensitivity of 0.708 and the specificity of 0.846. Conclusions:The main site of infection in patients with liver transplantation is respiratory system. Gram-negative bacilli are the main pathogens. When tacrolimus blood concentration is below 8.7 μg/L at two to four weeks after liver transplantation, the probability of infection in the early postoperative period may be reduced.