Hepatocellular carcinoma is the most common malignancy of the liver and poses serious health burdens on China and the whole world. However， most patients with hepatocellular carcinoma are already in the advanced stage at the time of diagnosis， with fewer opportunities for surgery and limited treatment options. In recent years， the advances in molecular targeted therapies have brought new hope for patients with advanced hepatocellular carcinoma. Among these therapies， lenvatinib is the second first-line drug after sorafenib approved by the US Food and Drug Administration for the treatment of advanced hepatocellular carcinoma， and it has attracted widespread attention for its powerful anti-tumor properties. However， the efficacy of lenvatinib is severely limited by its drug resistance. This article reviews the research advances in the molecular mechanisms of lenvatinib resistance in hepatocellular carcinoma and discusses possible ways to improve the efficacy of lenvatinib， so as to improve its efficacy.

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*

Objective:To evaluate the safety of two inactivated COVID-19 vaccines in a large-scale emergency use.Methods:Based on the "Vaccination Information Collection System", the incidence data of adverse reactions in the population vaccinated with the inactivated COVID-19 vaccines developed by Beijing Institute of Biological Products Co., Ltd and Wuhan Institute of Biological Products Co., Ltd, respectively, in emergency use were collected, and the relevant information were analyzed with descriptive epidemiological and statistical methods.Results:By December 1, 2020, the vaccination information of 519 543 individuals had been collected. The overall incidence rate of adverse reactions was 1.06%, the incidence rate of systemic adverse reactions was 0.69% and the incidence rate of local adverse reactions was 0.37%. The main systemic adverse reactions included fatigue, headache, fever, cough and loss of appetite with the incidence rates of 0.21%, 0.14%, 0.06%, 0.05% and 0.05%, respectively; the main local adverse reactions were injection site pain and injection site swelling with the incidence rates of 0.24% and 0.05%, respectively.Conclusion:The two inactivated COVID-19 vaccines by Beijing Institute of Biological Products Co., Ltd and Wuhan Institute of Biological Products Co., Ltd showed that in the large-scale emergency use, the incidence rate of general reactions was low and no serious adverse reactions were observed after the vaccinations, demonstrating that the vaccines have good safety.

Objective: The connectivity alterations in the putamen were found in revealing the neural correlates of attention-deficit/hyperactivity disorder (ADHD), but whether the effective connectivity of the putamen is atypical in ADHD remains unclear. Investigating this abnormality contributes to describing the neural circuit of ADHD at the level of macrostructural organization. Methods: Data were acquired from thirty-two boys with ADHD and fifty-two matched typically developing controls (TDC) from Peking University (Peking) dataset deposited at the Neuroimaging Informatics Tools and Resources Clearinghouse (NITRC) platform. We examined the effective connectivity of the putamen using Granger causality analysis (GCA) and then determined whether these connections could differentiate ADHD from TDC. Results: Compared with TDC, the ADHD group showed decreased effective connectivity from the left ventral rostral putamen (VRP) to left calcarine (CAL), right medial part of the superior frontal gyrus, left orbital part of superior frontal gyrus and left middle occipital gyrus (MOG). Increased effective connectivity from the left inferior occipital gyrus and right lingual gyrus to left VRP was also found in ADHD. The result of the classification accuracy showed that 72.3% of participants were correctly classified using support vector machine. Moreover, GCA values from the left VRP to left CAL and left MOG were significantly correlated with hyper/impulsive scores of patients with ADHD. Conclusion The findings may help extend our understanding of the ADHD-related neural loops.

Objective: The connectivity alterations in the putamen were found in revealing the neural correlates of attention-deficit/hyperactivity disorder (ADHD), but whether the effective connectivity of the putamen is atypical in ADHD remains unclear. Investigating this abnormality contributes to describing the neural circuit of ADHD at the level of macrostructural organization. Methods: Data were acquired from thirty-two boys with ADHD and fifty-two matched typically developing controls (TDC) from Peking University (Peking) dataset deposited at the Neuroimaging Informatics Tools and Resources Clearinghouse (NITRC) platform. We examined the effective connectivity of the putamen using Granger causality analysis (GCA) and then determined whether these connections could differentiate ADHD from TDC. Results: Compared with TDC, the ADHD group showed decreased effective connectivity from the left ventral rostral putamen (VRP) to left calcarine (CAL), right medial part of the superior frontal gyrus, left orbital part of superior frontal gyrus and left middle occipital gyrus (MOG). Increased effective connectivity from the left inferior occipital gyrus and right lingual gyrus to left VRP was also found in ADHD. The result of the classification accuracy showed that 72.3% of participants were correctly classified using support vector machine. Moreover, GCA values from the left VRP to left CAL and left MOG were significantly correlated with hyper/impulsive scores of patients with ADHD. Conclusion The findings may help extend our understanding of the ADHD-related neural loops.

Objective:To analyze the usage intention and key issues of medical staff to use telemedicine, for improving telemedicine service system in China.Methods:From October to November 2019, medical workers of both the inviting party and invited party who experienced telemedicine in seven provinces of Fujian, Hainan, Henan, Hunan, Guizhou, Sichuan and Qinghai were selected for an online questionnaire survey. Areas covered included their usage intention, satisfaction and cognitive appraisal of telemedicine. Descriptive statistical analysis and non-parametric test were used to discuss the intention of further use, satisfaction and challenges of medical workers in various provinces and regions.Results:1 084 valid questionnaires were recovered. The data found the overall satisfaction was 98.62%, and the proportion of their intention of further use was 98.25%, and those from the eastern and western provinces presented higher intention of usage. The top challenges as reflected by these medical workers were named as follows: timeliness of consultation progress and information feedback; long latency time; low Internet speed, poor and interrupted Internet signal; inadequate system equipments and inconvenient operation; difficulties in remote physical checkup and overall understanding of patient conditions; as well as substandard, incomplete and poor medical records.Conclusions:These medical workers are satisfied with the telemedicine services and willing to continue to use telemedicine.For those existing problems, it is suggested to strengthen the infrastructure and optimize the process of telemedicine services, so as to encourage them in greater use of telemedicine.

Objective:To analyze the actual and expected incentives and key issues of telemedicine providers in China and to provide important references for optimizing telemedicine incentive policies.Methods:The sample data came from a questionnaire survey of 1 084 providers in 7 provinces of Fujian, Hainan, Henan, Hunan, Guizhou, Sichuan and Qinghai in October and November 2019 and a semi-structured interview data at 6 hospitals in Henan province in January 2020. Descriptive analysis was used to sort such data into text data for classified summation.Results:The greatest gaps were found between actual incentives and expected ones in expense subsidies, title promotion and excellence awards, with such gaps as high as 18.65, 28.26, 29.28 percentages among providers of junior, deputy senior and senior academic titles respectively. Hospitals fall short in providing adequate incentives for telemedicine providers, not to mention lack of differentiation and diversification in personnel incentives, and poor implementation of incentive policies.Conclusions:It is suggested to strengthen incentive demand analysis, break the homogenization bottleneck of incentive policies, and consolidate internal publicity and implementation of incentive policies.

Objective:To assess the antibody persistence 3-5 years following vaccination of measles and rubella combined live-attenuated vaccine (MR) at 8 months of age and measles, mumps and rubella combined attenuated live vaccine (MMR) at 18 months of age.Methods:In 2016, 18-month-old children who were vaccinated with one dose of MR vaccine at the age of 8 months were recruited in Hebei Province as group 1; 4-, 5- and 6-year-old children who were vaccinated with one dose of MR vaccine at the age of 8 months and one dose of MMR vaccine at 18 months of age were recruited in Shanxi, Inner Mongolia and Beijing as group 2, group 3 and group 4, respectively. Serum samples were collected to detect IgG antibodies against measles, mumps and rubella by ELISA. Geometric mean concentrations (GMCs) of measles, mumps, and rubella antibodies were compared among groups by analysis of variance or non-parametric test. Seropositive rates were compared among groups by Chi-square test or Fisher′s exact test. Results:A total of 650 children were included in this study. Seropositive rates of measles, mumps and rubella antibodies 30 d after vaccination of 150 18-month-old children with one dose of MMR vaccine were 100%, 91.33% and 100%, respectively, and the GMCs were 1 846.87 mIU/ml, 299.91 IU/ml and 111.33 IU/ml, respectively. Seropositive rates of measles, mumps and rubella antibodies 3-5 years after vaccination one dose of MR vaccine at 8 months of age and one dose of MMR vaccine at 18 months of age were above 94%, 79% and 71%, respectively, and the GMCs were above 830 mIU/ml, 240 IU/ml and 31 IU/ml. No significant difference in the seropositive rates of the three antibodies was observed among groups 2, 3 and 4 ( P>0.05). There was no significant difference in the GMCs of measles or mumps antibodies among the three groups ( P>0.05), but the differences in the GMCs of rubella antibodies were statistically significant ( P=0.034). Conclusions:Measles, mumps and rubella antibodies persisted for 3-5 years without significant decrease after vaccination one dose of MR vaccine at 8 months of age and one dose of MMR vaccine at 18 months of age.

Objective: To investigate the influencing factors of the implementation of precision medical services based on clinician cognition, and provide a scientific reference for the implementation and advancement of precision medical services. Methods: Using electronic questionnaires, clinicians from 48 hospitals in 12 provinces(autonomous regions and municipalities directly under the Central Government) were surveyed from July to September 2019, with 341 valid questionnaires collected. Descriptive statistics and factor analysis were performed on the survey data. Results: Three dimensions that affect precision medical services were identified from the recovered questionnaires, namely external support factors, hospital drive capabilities, patient information provision and protection. The contribution rate of variance after orthogonal rotation was 35.157%, 22.234% and 16.343% respectively. Conclusions The external supporting factors should be developed, the hospital driving ability should be strengthened, and the patient information reception and privacy information security should be ensured to provide an important basis and guarantee for the implementation of precision medical service.

Telemedicine can optimize deployment of medical resources and minimize diagnosis discrepancies.Formulation of a rational project pricing and scientific compensation policy will be conducive to its future development. The concept of human resource consumption in RBRVS was used as reference to improve the activity-based costing ( ABC ) method. The authors sorted out the resource cost repository, identified the activity system, classified the motivation resources into respective activity cost repositories, and calculated the cost of respective cost object distribution.The cost of three telemedicine service items(remote single discipline consultation, remote image consultation and remote pathology consultation were 119.69, 147.03 and 161.61 yuan respectively) was calculated by the improved ABC.It can better indicate project costs than that calculated by the traditional ABC(137.30, 147.17 and 144.08 yuan), and proves more consistent with the existing prices of other province(134.00, 150.00 and 174.00 yuan).