Objective:Our aim was to To clarify the roles of p16 and p15 proteins in the genesis of acute lymphoblastic leukemia(ALL).Methods:Twenty-three samples of ALL were studied by the method of indirect immunofluorescence.Flow cytometer was used to estimate the cellular fluorescent intensity to determine the levels of p16 and p15 proteins.Results:Negative expression for p16 protein was found in 10 of 23 samples,and 8 of 23 were p15 negative expression.Both kinds of proteins were abscent in 6 samples.2 of 3 cases of T-ALL were negative expression of p16,p15 protein.In non T-ALL,6 of 13 were negative expression for p16 protein,5 of 13 were p15 protein deficient.The expression rates of p16,p15 protein in high leukocyte group were lower than those of non-high leukocyte group(P<0.05).The expression rates of p16,p15 proteins in HR-ALL were lower than those of SR-ALL(P<0.05).Conclusion:The p16 and p15 proteins take part in the genesis of ALL.Negative expression of p16,p15 proteins might imply the poor clinical outcome.

Objective To investigate the association between the nutritional status and related factors in patients with Parkinson's disease (PD).Methods Seventy-two patients with PD (PD group) and 71 age-and sex-matched healthy controls (control group) were enrolled in this study from September 2014 to November 2017 at the First Affiliated Hospital of Sun Yat-sen University.Their serum nutritional indices,including serum albumin,prealbumin,transferrin,free fatty acid and retinol conjugated protein,were collected.The PD participants were interviewed and assessed using motor and non-motor scales,including Hoehn and Yahr stage,Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS),Non-Motor Symptoms Questionnaire for Parkinson's Disease (NMSS),Mini-Mental State Examination (MMSE),Unified Dyskinesia Rating Scale (UDysRS) and 39-item Parkinson's Disease Questionnaire (PDQ-39).Their medication dosage was indicated by daily levodopa equivalent doses (LEDD).Body mass index (BMI) was used to determine their nutritional status,with abnormal nutritional status defined as BMI lower than 20 kg/m2.Results Levels of serum albumin (41.60 (40.28,43.98) g/L vs 44.00 (42.30,46.20) g/L,Z=4.500,P＜0.01),transferrin ((2.32±0.34) g/L vs (2.51±0.34) g/L,t=-3.305,P=0.001),and free fatty acid (418.00 (289.75,637.25) μmol/L vs 547.00 (386.00,699.00) μmol/L,Z=2.079,P=0.038) of the PD group were significantly lower than those of the control group.There was a significant negative correlation between serum albumin and MDS-UPDRS-Ⅱ score (r=-0.254,P=0.031),MDS-UPDRS-Ⅳ score (r=-0.256,P=0.030),years of dyskinesia (r=-0.240,P=0.043),years of motor fluctuation (r=-0.304,P=0.009) and LEDDs (r=-0.321,P=0.006).Disease duration was negatively correlated with serum albumin (r=-0.285,P=0.015) and transferrin (r=-0.275,P=0.019),and age (r=-0.252,P=0.032) was negatively correlated with prealbumin.The forward binary Logistic regression model indicated that abnormal nutritional status was closely associated with rigidity (OR=1.171,95％CI 1.013-1.354,P=0.032),akinesia (OR=1.070,95％CI 1.000-1.144,P=0.048),UDysRS score (OR=1.051,95％CI 1.004-1.099,P=0.032),MDS-UPDRS-Ⅳ score (OR=1.177,95％CI 1.018-1.360,P=0.027) and MMSE score (OR=0.821,95％CI 0.678-0.994,P=0.043),but not correlated with tremor and axial symptoms.Compared with PD patients with abnormal nutritional status,PD patients with normal nutritional status had higher MMSE scores (28.00 (27.00,29.00) vs 28.00 (25.00,28.00),Z=-2.060,P=0.039),lower rigidity (9.60±3.83 vs 12.00±4.29,t=-2.264,P=0.027),akinesia (19.98 ± 8.00 vs 24.42:±:8.06,t=-2.071,P=0.042) and MDS-UPDRS-Ⅳ scores (8.00 (5.00,11.00) vs 10.00 (9.00,13.00),Z=2.642,P=0.008).Conclusions PD patients tend to have a lower serum nutritional indices.PD patients with lower levels of serum nutritional indices are characterized by more severe motor complication,longer disease duration,older age and higher LEDD.PD patients with abnormal nutritional status have worse cognition and more severe motor symptoms (rigidity,akinesia and motor complication).

OBJECTIVE To prov ide reference for improving the participation mechanism of stakeholders in the process of medical insurance negotiation for oncology drug in China. METHODS Based on the stakeholder theory ，combined with literature research，case analysis （taking the review of reimbursement of Bentuximab as an example ）and other methods ，analysis and research were conducted on the Canadian oncology drug review process and the participation mechanism and role of stakeholders. The suggestions were put forward for our country. RESULTS & CONCLUSIONS Canadian oncology drug reimbursement review process was composed of four stages ：the pre-submission planning stage ，the formal submission stage of application，the review stage，and the stage of forming reimbursement recommendations. As the role of stakeholders ，drug manufacturers ，patient representative advisory group ， clinical review expert advisory groups and provincial advisory groups participated in the reimbursement review process of oncology drug by providing suggestions and feedback to CADTH. The participation of stakeholders had improved the transparency of the review of oncology drugs in Canada and made the reimbursement results of oncology drugs more scientific ，reasonable and accurate. In China ，it is recommended to define rights ，responsibilities and interests as well as the participation mechanism of stakeholders in the medical insurance negotiation process ，attach importance to the role of patients in the medical insurance negotiation process of oncology drug ，improve information disclosure and increase the transparency of the negotiation mechanism and process so as to increase the participation of stakeholders.

OBJECTIVE To compare the effect between drug donation model and national drug negotiated model on drug sales，and to provide reference for pharmaceutical enterprises to optimize their business strategies . METHODS Based on medical insurance statistics and settlement data of city A in Jiangsu province from 2013 to 2018，trastuzumab was selected as the representative drug . The sales and utilization of trastuzumab were compared during the implementation of the two models . At the same time ，the changes of medication behavior of some patients were analyzed . RESULTS After the implementation of drug donation model ，sales volume and turnover of trastuzumab increase by 193.87% and 155.71% in that year compared with the previous year ，and then the growth trend became stable ；after including the national negotiated drug list ，the number of users of trastuzumab in the year increased by 87.68% compared with the previous year ，and the sales volume increased by 48.06%；turnover increased by 22.81% even though the unit price decreased significantly . Both models could improve drug sales ，and the results of multiple linear regression also proved that different models had a significant impact on the consumption sum of trastuzumab in patients. CONCLUSIONS Under the condition that the unit price level of drugs is approximately the same ，both drug donation model and national drug negotiated model can increase the sales volume and expand the coverage of drugs . The latter reduces the drug threshold of patients ，and plays a positive role in improving the drug accessibility of patients and the sales and development of enterprises.

OBJECTIVE：To eval uate the effectiveness ，safety and economy of chimeric antigen receptor T cells （CAR-T） therapy for the treatment of B-lymphoblastic hematologic malignancy ，and to provide evidence-based reference for clinical decision. METHODS：Rapid health technology assessment （HTA）was adopted. PubMed ，Embase，Cochrane Library ，CNKI，Wanfang databases and foreign HTA official websites were systematically searched during the inception-Mar. 20th，2021. After inclusion ， data extraction and quality evaluation of literatures according to the inclusion and exclusion criteria ，descriptive analysis was performed for the effectiveness ，safety and economy of CAR-T therapy for the treatment of B-lymphoblastic hematologic malignancy. RESULTS ：A total of 2 HTA reports ，5 systematic reviews/Meta-analysis ，and 5 economics studies were included. In terms of effectiveness ，CAR-T therapy showed good efficacy in the treatment of B-lymphoblastic hematologic malignancy ；overall remission rate （ORR）of CAR-T therapy in the treatment of acute lymphoblastic leukemia was more than 63.5％，and the complete remission rate （CR）was 77.1％（95％CI：62.8％-87.1％）；ORR of CAR-T therapy in the treatment of chronic lymphoblastic leukemia was 70.0％（95％CI：53.0％-80.0％），and the CR was 25.5％（95％CI：13.9％-42.1％）；ORR of CAR-T therapy in the treatment of B-cell lymphoma was more than 44.4％. In terms of safety ，the incidence of cytokine release syndrome was more than 20％ during the treatment of CAR-T therapy ，and 1/3 or more （9％ believed in some studies ）patients suffered from neurotoxicity ； the incidence of infection was 12.2％-33.3％，and the incidence of graft-versus-host disease was 23.4％（95％CI：8.6％-49.8％）. In terms of economy ，most of the included studies believed that CAR-T therapy possessed economic advantages ，which were the results of evaluation in developed countries such as the United States and Japan. CONCLUSIONS ：CAR-T，as a new product of treatment for hematological malignancy ，shows good effectiveness and low level of ADR ，which is basically controllable ；its economy needs to be further evaluated by relevant researches combined with domestic reality.