Objective:To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial.Methods:We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models.Results:The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD 3) after induction therapy was independently associated with relapse risk ( HR=2.535, 95% CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk ( HR=1.869, 95% CI 1.034-3.379, P=0.039). Based on MRD 3 and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD 3-negative and IKZF1 gene deletion-negative) and high-risk (MRD 3-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % ( P<0.001) and (61.6±8.3) % vs (25.5±6.5) % ( P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS ( HR=3.937, 95% CI 1.975-7.850, P<0.001) and CIR ( HR=4.037, 95% CI 2.095-7.778, P<0.001) . Conclusion:The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.

Objective:To investigate the acute and long-term toxicity of GJ-4 extracted from Gardenia jasminoides J.Ellis, and to provide safety basis for its development as a new drug for the treatment of dementia. Methods:In the acute toxicity experiment, 30 ICR mice were randomly divided into control group, gardenia extract 2.5 g/kg group and gardenia extract 5.0 g/kg group, 10 mice in each group. The mice in the 2.5 g/kg and 5.0 g/kg gardenia extract groups were administrated with GJ-4 suspension. The control group was given 0.5% sodium carboxymethyl cellulose (CMC-Na) by gavage. The mice were given continuous gavage for 7 days. The mortality, body weight and general condition of mice were recorded. The levels of ALT, ALP, BUN and creatinine (CRE) in serum were measured by automatic biochemical detector. In the long-term toxicity experiment, 75 ICR mice were divided into control group and gardenia extract 100, 250, 500, 1 000 mg/kg group according to the random number table method, 15 mice in each group. The GJ-4 suspension of Gardenia extract 100, 250, 500 and 1 000 mg/kg were administrated to the stomach respectively in the gardenia extract 100, 250, 500 and 1 000 mg/kg groups, and 0.5% CMC-Na of the same volume was administrated to the stomach in the control group once a day for 30 days. The mortality, weight and mental state of mice were recorded. The organ index and the levels of ALT, ALP and BUN in serum were observed.Results:In the acute toxicity experiment, the mental state and diet of mice in each group were good, and there was no death within 7 days. Compared with the control group, there was no significant differences in body weight, heart index, liver index and kidney index between the two groups ( P>0.05). Compared with the control group, the level of BUN (10.17 ± 0.82 mmol/L vs. 11.25 ± 0.47 mmol/L) in the gardenia extract 2.5 g/kg group significantly decreased ( P<0.05), and the level of ALP (116.0 ± 10.75 U/L vs. 148.0 ± 25.73 U/L) in the gardenia extract 5.0 g/kg group significantly decreased ( P<0.05). In the long-term toxicity experiment, the mice were in good mental state and had good diet, and no death occurred. Compared with the control group, there was no significant differences in body weight, heart index, kidney index, spleen index and serum ALT, ALP and BUN levels between the two groups ( P>0.05). The liver index (4.9 ± 0.56 vs. 4.38 ± 0.49) in the 250 mg/kg gardenia extract group significantly increased ( P<0.01), and the thymus index (0.09 ± 0.02 vs. 0.14 ± 0.04) significantly decreased ( P<0.05). Conclusions:The Gardenia jasminoides extract GJ-4 has no obvious toxicity in acute and long-term toxicity experiment, indicating that GJ-4 is safe.

Wutou-Gancao herb-pair is extensively used to attenuate the toxicity and enhance the efficacy of aconite. In this study, potential synergic mechanism of the herb pair was investigated by utilizing multiple ap-proaches. In silico and in vitro Caco-2 cell models were applied to study the potential binding mode of bioactive ingredients existing in liquorice with P-glycoprotein (P-gp), as well as the inhibition effects on P-gp. Additionally, anti-inflammatory activity of aconitine (AC) combined with active ingredients of liquorice, as well as pharmacokinetic patterns of AC after co-administration was investigated. Anti-inflammatory effect of AC (1 mg/kg) in rats was enhanced in combination with bioactive ingredients of liquorice (10 mg/kg). In the meanwhile, the exposure of AC in vivo was altered, in terms of Cmax and AUC. For instance, the Cmax and AUC were increased to 1.9 and 1.3 folds, respectively, when used in combination with liquiritigenin. The in silico study revealed the potential binding mode with outward facing conformation of P-gp. The resulting data obtained from transport of rhodamine-123 (Rh-123) across Caco-2 cell monolayer further indicated that the function of P-gp was inhibited by chemicals in liquorice. The synergic effect was therefore proposed to be attributed to inhibition of P-gp by liquorice since AC has been demonstrated to be the substrate of P-gp. The resuls revealed that potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting function of key efflux transporter P-gp to enhance the exposure of AC in systematic circulation, and further the anti-inflammatory effect, which helps clarify the compatibility rationale of these two herbs.

Objective To study the inhibitory effects ofberberine on human organic cation transporter (OCTs) including OCT1,OCT2,OCT3,OCTN1 and OCTN2.Methods Using animal cell transgenic method mediated by transporter Lipo 3000,the drug transporters over expression cell lines S2-OCT1,S2-OCT2,S2-OCT3,S2-OCTN1 and S2-OCTN2 were obtained by selective medium culture.The OCTs evaluation model was established by detecting the trans-membrane transport of radioactive substrate in vitro.Wild type (WT) cells were used as control group,activity of OCTs was verified by adding its inhibitor.The inhibition of berberine on the transporters was investigated in vitro.The IC50 of inhibitory effect of berberine on various drug transporters was also calculated.Result The transport activity of transporter cell lines was increased by more than 5 times compared to the WT cell line respectively,what's more,their transport activity decreased significantly by their corresponding inhibitor.The ICs0 of berberine to OCT1,OCT2,OCT3,OCTN1 and OCTN2 were respectively 7.63,6.80,2.25,4.66 and 210.34 μmol/L.Conclusion Berberine significant inhibition to OCT1,OCT2,OCT3,OCTN1 and OCTN2.The inhibition on OCT1,OCT2,OCT3,OCTN1 is stronger compared to OCTN2.

Objective To study the inhibition of berberine on organ anion transporters (OATs) and its bidirectional trans-membrane transport.Method The transgene cell lines of the organ anion transporters including OAT1,OAT2,OAT3,OAT4,OAT7,and URAT1 were constructed and selected by animal cell transgenic method mediated by transporter Lipo 3000.Wild type (WT) cells were used as control group,and activity of OATs was verified by adding their radiolabeled substrates and inhibitors.The inhibition of 100 μmol/L berberine on the transporters was investigated in vitro.The IC50 of berberine on URAT1 was also determined.The bidirectional transport of berberine was studied through the Caco-2 model.Result The results showed that 100 μmol/L berberine inhibited the activity of OAT1,OAT2,OAT3,OAT4,OAT7 and URAT1 to (70.48±4.23)％,(69.13±1.28)％,(72.12±3.28)％,(79.77±6.49)％,(69.51 ±5.99)％ and (38.4 ± 2.67)％ respectively,the IC50 of berberine to URAT 1 was 13.19 μmol/L,the Papp (A-B) of 50 μmol/L and 100 μmol/L berberine were separately 0.28 × 10-6 and 0.40 × 10-6 cm/s,and the effiux rates were separately 3.18 and 3.15.Conclusion Berberine shows a stronger inhibition to URAT1 compared to OAT1,OAT2,OAT3,OAT4 and OAT7.Berberine may be the substrate of some effiux transporters.This study provides theoretical basis for explaining the low bioavailability ofberberine and forecasting the possible drug-drug interaction.

Objective:To analyze pharmaceutical procurement model of hospital, and explore better pharmaceutical procurement model so as to suit the development of modern hospital.Methods: Combined with the current situation of pharmaceutical procurement in domestic medical organization in recent years to analyze the current problems that existed in pharmaceutical procurement of hospital management.Results: Aimed at the problems that existed in procurement management model in current hospital, the reasonable suggestions have been proposed, and these suggestions have provided reference and experience forpharmaceutical management and procurement in hospital.Conclusion: Pharmaceutical procurement is the material basis of pharmaceutical supply of pharmaceutical trading enterprise, and it is the start point of pharmaceutical circulation and distribution, and it also is the first important step. Especially, aimed at the institutional reform of separating pharmacy from clinic in Beijing, the normalization of pharmaceutical procurement management will be very important effect in working practice.

Objective To establish a method for the quantitative analysis of multi-component with a single-marker (QAMS) to determine the contents of four rhubarb anthraquinones inShanzha Xiaozhi capsules; To conduct methodology investigation.Methods Emodin was set as the internal reference substance, and the relative correlation factors of aloe emodin, rhein, chrysophanol to emodin were calculated and evaluated. The contents of these four anthraquinones were determined by the external standard method and QAMS, respectively. Rationality, feasibility and repeatability of the QAMS method were verified by comparing the results obtained from the two different methods. Results The QAMS method and HPLC method did not show significant difference in results.Conclusion QAMS method can be used as a quality assessment model for quantity evaluation of anthraquinones inShanzha Xiaozhi Capsules.

Objective To study the relationship among the angiotensinogen (AGT)gene T174M,M235T polymorphisma,blood glucose level and atherosclerotic cerebral infarction.Methods The polymerase chain reaction-restriction fragment length polymor-phism (PCR-RFLP)method was adopted to detecte the gene polymorphisms of AGT gene 174,235 sites and the fully automatic bi-ochemical analyzer was used to detect the biochemical indexes of GLU,etc.in 396 patients with atherosclerotic cerebral infarction and 360 normal controls.Results The GLU level in the patients of the ACI group carrying genotype TT and TM at AGT gene T174M site was higher than that in the normal control group with statistical differences(P <0.05),the glucose level had no statisti-cal difference between the different 2 kinds of genotype (P >0.05);the glucose level in the patients carrying genotypes MM,MT and TT at M235T site in the ACI group was higher than that in the normal group,and the difference was statistically significant(P<0.05).The blood glucose level between the two groups carrying 2 different kinds of genotype showed no statistically significant difference (P >0.05 ).Conclusion No correlation is found among AGT gene T174M,M235T polymorphism,blood glucose level and atherosclerotic cerebral infarction;hyperglycemia is one of the risk factors of atherosclerotic cerebral infarction occurrence.

Objective To Investigate the relationship between an in sertion (I)/deletion (D) polymorphism for angiotensin converting enzyme (ACE) and A(1166)C Polymorphism of angiotensin type 1 receptor(AT 1R) genes in patients with vertebro basilar insufficiency(VBI). Methods In this study, We examined 120 patients with VBI and 146 normal controls. The genotype for I/D of ACE and A(1166)C of AT 1R was assessed using polymerase chain reaction (PCR) and refrained fragment length polymorphism(RFLP), respectively. Then we compared the genotype frequency distribution among subjects.Results As a whole, there was significant difference in the distribution of ACE (I/I, I/D and D/D) and AT 1R (A/A and A/C), respectively. D allele frequency was higher in patients compared with the normal controls. Our study also revealed that Ⅱ AA and DD AA genotype frequency in VBI was higher than that in the normal controls.Conclusion The D allele for ACE and C(1166) allele of AT 1R may correlated with VBI.Ⅱ genotype for ACE and AA genotype had a positive con influence on the VBI. The affection of DD AA genotype on VBI was negative.

OBJECTIVETo establish three orthotopically transplanted model of human primary malignant spleen lymphoma in the nude mice.

METHODSOrthotopic transplantation of histologically intact human primary malignant splenic lymphoma tissue obtained from patients was introduced into the splenic parenchyma of nude mice. Tumorigenicity, invasion, metastasis and morphological characteristics of the transplanted tumor were studied by light microscopy, electron microscopy and immunohistochemical methods.

RESULTSThe first kind, a strain of human primary malignant spleen lymphoma (non-Hodgkin's, cleaved B cell, BFNHL-HMN-1) screened from 11 patients which had been passaged in vivo for 41 generations, a second kind, a liver metastasis model of human primary malignant spleen lymphoma (non-Hodgkin's, cleaved B cell, LM-BFNHL-HMN-2) which had been passaged for 47 generations and a third kind of human primary malignant spleen lymphoma (non-Hodgkin's, T-immunoblastic cell, TINHL-HMN-3) having passaged for 37 generations were all successfully transplanted in 611 nude mice. Models of BFNHL-HMN-1 and TINHL-HMN-3 tumor gave nodular growth and lymph node metastasis in the spleen hilum but without any metastasis in the abdominal lymph nodes or organs. In the LM-BFNHL-HMN-2 model, not only did the tumor cells grow in the spleen, but in spleen hilum, lymph nodes and liver also. The orthotopically transplanted tumor cells were similar to the original human tumor in light histopathology, ultrastructure features, DNA content and chromosomal karyotype.

CONCLUSIONThese three models are able to serve as useful tools for the study of biologic characteristics and experimental treatment of human primary malignant lymphoma.

Animals ; Disease Models, Animal ; Humans ; Lymphoma ; pathology ; Mice ; Mice, Nude ; Neoplasm Metastasis ; Neoplasm Transplantation ; Splenic Neoplasms ; pathology ; Xenograft Model Antitumor Assays