Objective To investigate the induction of B-cell specific phenotype in classical Hodgkin lymphoma (cHL)upon all-trans retinoic acid(ATRA)incubation. Methods To construct B-cell specific promoter(CD19, CD79a,CD79b)driven reporter plasmid with NEO cassette to realize stable transfection and selection of cHL reporter cells. To verify the intact integration by amplification of the promoter and luciferase sequences,and to functionally validate the B-cell specific promoter by ABF1 interference and luciferase assay. Repoter cells were incubated with various doses of ATRA and luciferase activity was detected at 24,48 and 72 hours. Reporter cells were treated alone or in combination with 5-Aza and ATRA followed by luciferase assay. Endogenous B-cell specific genes(CD19, CD20, CD79a and CD79b) transcription and expression levels were detected by real-time PCR and immunoblot, respectively. The expression level of CD30 antigen on Hodgkin lymphoma cell membrane upon ATRA was assessed by flow cytometry. Results ATRA treatment stimulated B-cell specific signature in cHL cells including CD19,CD79a and CD79b while down-regulated their CD30 expression. Conclusions ATRA induces B-cell phenotype deficient cHL cells to regain their B-cell transcriptional program while abolishes their Hodgkin-specific machinery.

Objective To investigate the diagnostic value of dual-energy CT virtual non-contrast (VNC) technology for osteoporosis(OP). Methods Dual-energy CT images of 50 patients with lumbar traumas were collected prospectively.Patients who suffer from vertebral bodies fractures between lumbar 1 to 4, have internal metal fixations or underwent percutaneous vertebroplasty, or presented tumors or compromised bone metabolism induced by diseases or medications were excluded.The scanning range was from the upper edge of the 12th thoracic vertebral body to the lower edge of the first sacral vertebral body. The voltages of tubes A and B were 90 kV and Sn 150 kV,and the reference tubes currents were 220 mAs and 138 mAs. Image reconstruction was performed using Advanced Modeled Iterative Reconstruction (ADMIRE)with iterative strength of 3 and convolution kernel of Qr 40.The default parameters of the virtual non-contrast software were corrected by the standard recommended by the Bone Marrow software of the post-processing platform Syngo.via,and the CT value of calcium(contrast media CM),the CT value of mixed energy images(regular CT value,rCT),the calcium density(CaD)and the fat fraction(Fat)were measured. The bone mineral density (BMD) and T score of each lumbar vertebra from lumbar 1 to lumbar 4 were measured by dual energy X-ray absorptiometry(DXA).With T score less than or equal to the 2.5 standard deviation as the gold standard for the diagnosis of OP,correlations between CT measurements and vertebral BMDs were analyzed using Pearson correlation analysis and linear regression and the diagnostic values of different CT measurements for OP were compared using receiver operating characteristic curve. Results Each of the vertebral bodies was analyzed as a single unit.Fifty of them were osteoporotic and the rest 116 were non-osteoporotic.Except for Fat,the CT measurement parameters of the osteoporotic vertebral bodies were lower than those of the ones without osteoporosis, and the difference was statistically significant (P<0.01).CM,rCT and CaD were significantly correlated with BMD(r were 0.75,0.65,0.71,all P<0.01)and there was a linear relationship(F were 209.91,120.24,167.69,all P<0.01).Meanwhile,CM,rCT,CaD and T score were also significantly correlated (r were 0.74, 0.65, 0.70, all P<0.01) with a linear relationship (F were 195.04,120.29,156.37,all P<0.01).CM,rCT and CaD had relatively high concordance rates against the OP diagnosis gold standard (respectively 81.9%, 62.2% and 81.9%). CM and CaD had higher concordance rates than rCT,the difference being statistically significant(P<0.01),and by the CM less than 239.5 HU or CaD less than 10.9 mg/cm3standard, their sensitivities of diagnosing osteoporosis were respectively 86.0% and 84.0%,while the specificities,80.2% and 81.0%.After superimposing CM and CaD, the results did not improve the diagnosis efficiency of OP (pre-superposition diagnostic performance better than post-superposition (P<0.05). Conclusion The VNC technology on DECT can do both vertebral fractures diagnosis and osteoporosis assessment at the same time, thus optimizing the clinical examination process.

OBJECTIVE：To analyze the clinical manifestations and characteristics of adverse drug reactions （ADR）induced by EGFR-TKI，and to provide reference for safe use of drugs in clinic. METHODS ：The relevant data of EGFR-TKI-induced ADR reports which were reported to Shandong ADR Monitoring Center from January 2018 to December 2020 were summarized ，and analyzed statistically in respects of age ，gender，drug variety ，ADR classification ，usage and dosage ，occurrence time ，involved organs/systems，clinical manifestations and prognosis of patients. RESULTS & CONCLUSIONS ：A total of 120 ADR reports induced by EGFR-TKI were included ，involving 120 patients. Among 120 patients，the female （60.83％）was more than the male （39.17％），and the age was mainly 50-79 years old （79.16％）. A total of 5 drugs including gefitinib ，ositinib，afatinib，ektinib and erlotinib were involved. ADR occurred in 72，11，15，6 and 16 patients using the above drugs respectively ；the main ADR was general ADR （70.83％），followed by severe ADR （22.50％），new general ADR （5.00％）and new severe ADR （1.67％）. All patients were given drugs orally ，off-label use was found in 2 patients who used ektinib ，and the rest met the medication requirements of the drug instructions. ADR occurred in 61 patients（50.83％）within 1 month after medication ，34 patients （28.33％）within 1-3 months after medication ，25 patients（20.83％）within 4-12 months after medication ，and no ADR occurred after 12 months. ADR of organs/systems involved were mainly the lesion of skin and its appendant injury，gastrointestinal system injury and hepatobiliary system injury. The main clinical manifestations were rash ，diarrhea and abnormal liver function ；in addition，some patients developed severe or new severe ADR such as interstitial pneumonia ，bone marrow suppression ，tongue swelling and cerebral infarction. Totally 102 patients recovered or improved after drug withdrawal or symptomatic treatment ，12 patients had unknown outcome ，and 6 patients did not improve. It is suggested that pharmaceutical care should be strengthened within 1 month after EGFR-TKI administration ，so as to guard against the occurrence of new and serve ADR and ensure the safety of clinical medication.

OBJECTIVE：To investigate the occurrence and characteristics of new adverse drug reactions （ADR）in Shandong province，so as to provide reference for the safety of drug use in the clinic. METHODS ：The data of new ADR reports were collected from Spontaneous Reporting System of Shandong ADR Monitoring Center during Oct. 2019 to Mar. 2020. Those reports were analyzed statistically in respects of report types ，reporting institution ，reporters’occupation，gender and age of patients ，drug type ，organs/ systems involved ，clinical manifestations. RESULTS & CONCLUSIONS ：A total of 8 566 new ADR reports were screened out ， accounting for 10.81％ of the effective ADRs. Among them ，there were 7 961 new and general ADR （92.94％）and 605 new and serious ADRs （7.06％）. For the new ADR ，the reporting institutions were mainly medical institutions （98.42％），and the reporters ’ occupation were mainly doctors （78.44％）. Female （4 860 cases）was slightly more than male （3 698 cases）；most of them were 45 years old and above （70.00％），and intravenous drip （47.67％）was the main route of administration. The top five ADR suspected drugs were TCM preparations （34.50％），anti-microbials（13.75％），circulatory system drugs （11.41％），nervous system drugs （6.39％）and blood system drugs （4.81％），involving 517，91，64，53，50 types，respectively，among which Levofloxacin injection caused the most serious ADR （24 cases）. The new and general ADR mainly involved gastrointestinal system ，skin and its appendant ； their clinical manifestations were nausea ，vomiting，rash，etc. New and serious ADR mainly caused systemic damage ；their clinical manifestations were anaphylactic shock ，chest tightness and shivering ，etc. It is suggested to strengthen the ADR monitoring of TCM preparations，anti-microbials，circulatory system drugs and other drugs ，so as to ensure the safety of clinical drug use.

OBJECTIVE To prepare Angelica•Cinnamomum（Angelica sinensis-Cinnamomum cassia ）self•microemulsion drug delivery system （AC•SMEDDS），and to optimize its formulation and characterize its preparation . METHODS Using Angelica• Cinnamomum mixed volatile oil as oil phase and model drug ，on the basis of selecting emulsifier and co -emulsifier and the optimization of their mass ratio range ，the formulation was optimized with central composite design •response surface methodology using the ratio of oil phase （Angelica•Cinnamomum mixed volatile oil ），mass ratio of emulsifier and co -emulsifier as factors ，the comprehensive score of volatile oil content ，particle size and emulsifying time as index . Morphology，particle size ，drug loading ， entrapped efficiency and stability of optimized AC•SMEDDS were characterized . RESULTS The optimum formulation of AC•SMEDDS contained the ratio of oil phase was 30%，and the mass ratio of emulsifier （EL•40）and co -emulsifier（ethanol）was 9∶1. Results of validation tests showed that the average particle size of AC•SMEDDS was （148.33±1.53）nm，and emulsifying time was （18.44±0.11）s. The comprehensive score was 0.68，relative deviation of which from the predicted value （0.70）was 2.86%. AC•SMEDDS prepared by optimal formulation was faint yellow ，uniform and transparent liquid ，and spherical particals with translucent edge were observed under transmission electron microscope . Calculated by ligustilide and cinnamaldehyde ，the drug loading was （7.58±0.03） and （4.17±0.01） mg/g，and entrapped efficiency was （93.25±0.01）% and （88.89±0.02）% ， respectively. No stratification or precipitation occurred after centrifugation at the speed of 10 000 r/min or placing within 7 （No.2019-0520） days at 4 and 25 ℃ . The contents of ligustilide and cinnamaldehyde were stable . Its particle size had no significant change after 50，100 and 200 times dilution by purified water . CONCLUTIONS AC•SMEDDS is prepared successfully and its formulation is optimized . The stability of the preparation is good .