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 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 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 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 urodynamic characteristics in Parkinson's disease(PD)versus multiple system atrophy(MSA)patients with lower urinary tract symptoms(LUTS).Methods:We performed a retrospective study in PD and MSA patients admitted to the First Affiliated Hospital of Zhengzhou University and undergone urodynamic examinations from January 2016 to June 2019.A total of 178 patients, mean age(59.2±9.7)years were enrolled, with 64 PD patients, 74 MSA patients and 40 normal controls.Urodynamic parameters included maximum flow rate(Qmax), post-voided residual urine volume(PVR), bladder compliance(BC), overactive bladder(OAB), maximum cystometric capacity(MCC)and detrusor pressure at maximum flow rate(PdetQmax). Bladder function was assessed.Results:Frequent urination(68.8%)was the most common LUTS in PD patients, as opposed to urinary retention(91.9%)in MSA patients.The Qmax, PdetQmax and incidence of OAB were higher and the PVR were lower in PD patients than in MSA patients [free-flow(FF)-Qmax: (13.5±7.1)ml/s vs.(10.1±5.2)ml/s, U=26.98, P<0.01]; pressure-flow study(PFS)-Qmax: [(13.6±5.7)ml/s vs.(10.5±3.3)ml/s, U=34.90, P<0.01]; PFS-PdetQmax: [(23.9±11.3)cm H 2O vs.(16.3±8.6)cmH 2O, U=35.04, P<0.01]; OAB: (46.9% vs.27.0%, χ2=5.85, P<0.01); FF-PVR: [(30.4±20.0)ml vs.(161.7±79.8)ml, U=-71.81, P<0.01]; PFS-PVR: [(65.9±30.7)ml vs.(212.6±83.0)ml, U=-65.29, P<0.01]. Compared with the control group, the incidences of OAB and PFS-PVR were increased and the MCC and PdetQmax were decreased in the PD group(OAB: 46.9% vs.7.5%, χ2=6.15, P<0.018); PFS-PVR: [(65.9±30.7)ml vs.(22.2±10.4)ml, U=47.25, P<0.01]; MCC: [(305.1±79.7)ml vs.(389.6±65.2)ml, U=-52.13, P<0.01]; PdetQmax: [(23.9±11.3)cmH 2O vs.(37.3±10.3)cmH 2O, U=-49.88, P<0.01]. Compared also with the control group, the MSA group had a lower Qmax, PdetQmax and MCC, FF-Qmax: [(10.1±5.2)ml/s vs.(16.3±4.7)ml/s, U=-50.11, P<0.01]; PFS-Qmax: [(10.5±3.3)ml/s vs.(13.1±5.0)ml/s, U=-27.54, P<0.05]; PdetQmax: [(16.3±8.6)cmH 2O vs.(37.3±10.3)cmH 2O, U=-84.92, P<0.01]; MCC: [(284.3±71.8)ml vs.(389.6±65.2)ml, U=-39.31, P<0.01], a higher PVR, lower bladder compliance(BC)and a higher incidence of OAB(FF-PVR: [(161.7±79.8)ml vs.(22.0±13.0)ml, U=84.82, P<0.01]; PFS-PVR: [(212.6±83.0)ml vs.(22.2±10.4)ml, U=112.54, P<0.01]; BC: (28.4% vs.7.5%, χ2=6.81, P<0.01); OAB: (27.0% vs.7.5%, χ2=17.62, P<0.01). Conclusions:PD and MSA patients with LUTS have bladder dysfunction.MSA patients have more serious bladder dysfunction than PD patients.

Objective:To investigate the urodynamic characteristics in parkinsonian-type multiple system atrophy (MSA-P) and Parkinson′s disease (PD) patients with lower urinary tract symptoms (LUTS) and to identify the differential diagnostic ability of urodynamic study.Methods:Sixty-eight MSA-P patients and 85 PD patients with LUTS who underwent urodynamic studies and were hospitalized in the First Affiliated Hospital of Zhengzhou University from February 2017 to December 2020 were reviewed. The receiver operating characteristic (ROC) curve was used to evaluate the discriminatory power of urodynamic parameters.Results:Compared with PD, patients with MSA-P had shorter disease duration [2.70 (2.05, 3.00) years vs 5.00 (4.00, 6.00) years, Z=-7.44, P<0.001]. In free uroflowmetry (UFM) and pressure-flow study (PFS), patients with MSA-P showed lower maximal flow rate [Qmax; UFM-Qmax 6.00 (3.00, 8.75) ml/s vs 9.00 (6.00, 14.00) ml/s, Z=-4.31, P<0.001; PFS-Qmax[6.00 (3.00, 8.75) ml/s vs 9.00 (6.00, 14.00) ml/s, Z=-4.03, P<0.001] and larger postvoid residual [PVR;UFM-PVR 207.50 (113.75, 280.00) ml vs 45.00 (10.00, 117.50) ml, Z =-6.03, P<0.001; PFS-PVR 269.00 (148.75, 337.50) ml vs 75.00 (20.00, 167.50) ml, Z=-6.55, P<0.001)] with decreased compliance [42.65% (29/68) vs 14.12% (12/85), χ 2=15.68, P<0.001], decreased detrusor pressure at maximun flow rate [PdetQmax; 13.00 (6.00, 27.75) cmH 2O vs 27.00 (15.00, 39.50) cmH 2O, Z=-4.65, P<0.001; 1 cmH 2O=0.098 kPa] and impaired contractility [43.00 (34.00, 59.25) vs 79.00 (46.50, 100.00), Z=-5.44, P<0.001]. Compared with the MSA-P patients, detrusor overactivity (DO) was prominent in PD [54.41% (37/68) vs 78.82% (67/85), χ 2=10.34, P=0.001]. The ROC curve results showed that PFS-PVR had highest area under the curve (AUC), which was 0.81 (95% CI 0.74-0.88, P<0.001), followed by UFM-PVR, bladder contractility index and PdetQmax (0.78, 0.76 and 0.72, respectively). Conclusions:Patients with MSA-P showed lower Qmax and larger PVR with decreased bladder compliance and impaired contractility, while patients with PD had higher incidence of DO. The ROC results showed that PFS-PVR had the highest AUC and specificity in the differential diagnosis of MSA-P and PD,indicating that urodynamic study is a useful tool in differential diagnosis of patients with MSA-P and PD with lower urinary tract symptoms.