Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Encapsulated papillary carcinoma(EPC)of the breast is a rare,low grade malignant tumor which is more common in postmenopausal women.The clinical manifestations of EPC are non-specific and easily confused with other benign breast tumors,leading to misdiagnosis and delayed diagnosis.There is currently no consensus on the diagnosis and treatment plan for EPC,and few clinical trials have been conducted on it.Therefore,this article reviews the diagnostic characteristics and therapeutic approaches of EPC.

[Purpose]To analyze the incidence and mortality of thyroid cancer in Gansu cancer registration areas in 2019 and the trends from 2010 to 2019.[Methods]The data of thyroid can-cer from 2010 to 2019 were collected from 23 cancer registries in Gansu Province and the data quality was evaluated.The crude incidence/mortality rates,age-standardized incidence/mortality rates by Chinese standard population(ASIRC,ASMRC)and world standard population(ASIRW,ASMRW)and cumulative rate(0～74 years old)were calculated.The annual percentage change(APC)and average annual percentage change(AAPC)were calculated with Joinpoint software to analyze the trends of the incidence and mortality from 2010 to 2019.[Results]In 2019,the crude incidence of thyroid cancer was 6.89/105,the ASIRC was 5.50/105,the ASIRW was 5.33/105 and the cumulative rate(0～74 years old)was 0.48％in 2019.The crude mortality rate of thy-roid cancer was 0.42/105,ASMRC was 0.27/105,ASMRW was 0.31/105,cumulative rate(0～74 years old)was 0.03％.Incidence and mortality rates gradually increasing at age 30 and 55,re-spectively,reaching the peaks in the 45～49 and 60～64 age groups,respectively.Chengguan Dis-trict of Lanzhou City had the highest incidence rate,and Gulang County had the highest mortality rate.From 2010 to 2019,the AAPC of ASIRC of thyroid cancer was 17.12％(95％CI:7.52％～30.42％,P＜0.05)showing an upwards trend;while that of ASMRC was-3.64％(95％CI:-15.67％～10.10％,P＞0.05)showing a downward trend,but the change was not statistically significant.[Conclusion]The overall incidence of thyroid cancer in Gansu cancer registration areas is on the rise,and the prevention of high-risk groups should be strengthened.

OBJECTIVE To provide re ference for accurate measurem ent of population health status ，pharmacoeconomic evaluation and guidance of health resource allocation. METHODS Using quota and convenient sampling ，five administrative villages were selected from the rural areas under the jurisdiction of Liuzhi special zone ，Qianxi city and Jianhe county of Guizhou province from July to September 2020. Based on the gender and age ratio quota of rural population in the results of the national census，330 respondents were selected for questionnaire survey. The contents of the questionnaire included the self-made scale containing sociodemographic characteristics and general health information ，five-level EuroQoL five-dimension questionnaire （EQ-5D-5L，hereinafter referred to as the “new dimension scale ”）with cognitive dimensions （including attention ，memory， computing ability and learning ability ）and mini-mental state examination （MMSE）. The effects of reliability ，validity and new dimensions of new dimension scale on respond ents’quality of life were investigate ，and its measurement characteristics were verified；the application value of it in pharmacoeconomic hy_cheer@126.com evaluation and guiding the allocation of health resources were explored. RESULTS A total of 330 questionnaires weredistributed，320 were recovered and 320 were effective. The recovery rate and effective rate were 96.97％ and 100％ respectively. The ceiling effect of new dimension scale was 13.44％，the split-half reliability was 0.821，and the overall Cronbach ’s α was 0.852. Exploratory factor analysis showed that the new dimension scale was loaded with physiological ，cognitive and psychological factors ，and the cumulative contribution rate was 69.35％. The correlation coefficient between the new dimension and the dimension of MMSE scale were 0.19-0.61，showing a moderate or medium to strong correlation （P＜0.01）. Compared with EQ- 5D-5L，after adding each dimension ，the interpretation ability of the regression model was improved by 5.00％-17.50％. CONCLUSIONS The new dimension scale has high feasibility ，good reliability and validity ，significantly reduces the ceiling effect of EQ- 5D-5L，has higher sensitivity to the evaluation of people ’s quality of life，and can better evaluate the quality of life of rural population. It is suggested that it can be applied for quality of life evaluation，intervention effect analysis and related economic evaluation.

OBJECTIVE To provide the suggestions for improving t he enthusiasm of the public to report adverse drug reactions （ADRs），promoting pharmaceutical manufacturers to improve the smoothness of ADR reporting channels by the public and the enthusiasm of assuming the main responsibility for drug safety ，and to provide reference for the performance of drug safety supervision by regulatory departments in China. METHODS Taking 180 pharmaceutical manufacturers that had entered the top 1 000 in the world as the objects ，the questionnaire was prepared to investigate the smoothness of ADR reporting channels through 4 channels：contact number ，e-mail，official website and new media （including Wechat and microblog ） of enterprise . The questionnaire involved the establishment of public reporting channels ，the records and the feedback of enterprises. The existing problems were analyzed and suggestions were put forward. RESULTS & CONCLUSIONS More than 70％ of pharmaceutical manufacturers in China had established the channels for reporting ADR by the public ，which were mainly regular channels such as contact numbers and e-mail ，and each channel had the phenomenon that ADR information couldn ’t be reported. More than 60％ of the public channels established by manufactures lacked inquiry and supplement for the miss ing part of th e reported information ； only 24 pharmaceutical manufacturers provided feedback on ADR information ，and the feedback contents were monotonous. gywf2021-11It is suggested that pharmaceutical manufacturers should pay more attention to ADR monitoring among the public ，consider increasing multiple reporting channels while ensuring the smoothness of channels ，strengthen the training of employee ’s information collection ability to improve the quality of information ，timely feed back the ADR information reported by the public ， and increase the feedback content concerned by the public.

Objective:To screen the factors that were conducive to prolonging the effective half-life of 131I, and to provide a basis for selecting more suitable patients for the treatment of hyperthyroidism with lithium carbonate assisted radioactive 131I. Methods:Between July 2017 and March 2019, a total of 61 patients (23 males, 38 females, age: 13-73 (37.7±1.9) years) who received lithium carbonate adjuvant therapy before 131I treatment in the First Affiliated Hospital of Zhengzhou University were collected into this prospective study. Clinical parameters (serum free triiodothyronine (FT 3), serum free thyroxine (FT 4), iodine uptake rate (2 h, 12 h, 24 h) and ratio of iodine uptake rate (2 h/24 h, 4 h/24 h) before and after taking lithium carbonate were compared by using paired t test. The factors which were conducive to prolonging the effective half-life of 131I were analyzed by linear and multiple regression analyses. Results:Compared with the pretreatment results, lithium carbonate treatment significantly improved the 24 h iodine uptake rate ((74.82±2.69)% vs (82.38±2.33)%; t=2.674, P=0.010), decreased the ratio of 4 h/24 h iodine uptake rate ((88.96±2.85)% vs (82.12±2.27)%; t=2.644, P=0.010), prolonged the effective half-life of 131I ((123.03±3.09) vs (130.38±2.49) h; t=2.656, P=0.010), and decreased serum FT 3 ((26.46±1.65) vs (21.31±1.42) pmol/L; t=3.421, P=0.001) and serum FT 4 ((56.59±2.12) vs (49.24±2.19) pmol/L; t=3.289, P=0.002). Linear regression analysis showed that 2 h and 4 h iodine uptake rate, the ratios of 2 h/24 h and 4 h/24 h iodine uptake rate, and effective half-life of 131I before lithium carbonate treatment were related to the effective half-life of 131I after lithium carbonate treatment ( b values: from -0.576 to 0.642, all P<0.05). Multiple linear regression analysis showed that the ratio of 4 h/24 h iodine uptake rate was the main factor affecting the effective half-life of 131I after taking lithium carbonate ( b=0.642, 95% CI: 0.453-0.832, P<0.001). Multiple linear regression equation was y=-49.785+ 0.642 x. Lithium carbonate treatment could prolong the effective half-life of 131I if the ratio of 4 h/24 h iodine uptake exceeded 77.55%. Conclusion:The ratio of 4 h/24 h iodine uptake rate is the main factor affecting the change of the effective half-life of 131I after lithium carbonate treatment, and patients with hyperthyroidism whose ratio of 4 h/24 h iodine uptake rate exceeds 77.55% can effectively prolong the effective half-life of 131I after taking lithium carbonate.

Family physicians contracted service is an important choice to deepen the reform of China′s healthcare reform and achieve the strategic goal of " health for all" . In order to effectively promote the contracted service, the central government has successively issued a number of policy documents, which are echoed by the localities in their proactive explorations, achieving remarkable results. But there are also multiple roadblocks hindering the contracted service to progress. This article referred to the three-circle theory and studied policy implementation from the three dimensions of policy value, policy resources, and policy impetus. A thorough analysis of the problems in the implementation process revealed such main problems as insufficient family physicians, inadequacy of supporting policies and low level of policy acceptance among the young healthy age groups. The follow-up work will promote the long-term implementation of the family physicians contracted service policy by enriching the family physicians team, enriching supporting policies, and focusing on promotions to key age groups.

Objective:To develop an evaluation index system for dynamic adjustment effect of medical service prices in public hospitals, as a set of quantitative evaluation tools for management departments to keep track of the trend in time, implement dynamic monitoring and guide decision-making.Methods:Based on the evaluation system of price adjustment effect, through the importance assessment of expert consultation and multiple index percentile method, the scoring criteria were formulated and the empirical analysis was carried out.Results:The total scores of hospital A and hospital B were 71.31 and 77.94 respectively, classified as " average" . The evaluation could basically reflect the effect of dynamic adjustment of medical service price in public hospitals.Conclusions:The evaluation has the functions of displaying differences, witnessing achievements and tracing causes. It can be used to evaluate the effect of dynamic adjustment of regional prices, to assist the regulators to keep track of trends, monitor dynamically and guide decision-making in time, and be used by hospitals in self-evaluation to find problems, improve their own operation and promote the healthy development of hospitals.

Objective: To construct an index system for evaluating the effectiveness of dynamic pricing adjustment of medical services, for the purpose of providing a set of evaluation tools for price regulatory authorities to evaluate the effectiveness of pricing adjustment of medical services, to keep track of pricing trends, to implement dynamic monitoring and to guide decision-making. Methods: Oriented to public hospitals in Guangdong province, literature analysis and Delphi method were used to construct the index system for evaluating the effectiveness of dynamic adjustment of medical service price. Descriptive analysis, consistency test and index importance evaluation were applied to statistical analysis. Results: Thirty-two experts evaluated the importance of 41 alternative indicators. The index system for evaluating the effectiveness of dynamic adjustment of medical service price was finally constructed, including six structural indicators, six process indicators and six result indicators. Conclusions Experts are representative, authoritative and well-coordinated. The consultation results are reliable. The evaluation index system has high reliability and validity, and can be used to objectively evaluate the dynamic adjustment effect of medical service price.