[Efficacy and safety of daratumumab in patients with relapsed/refractory multiple myeloma].

Objective: To investigate the efficacy and safety of daratumumab in relapsed/refractory multiple myeloma (RRMM) patients. Methods: Fifty-two RRMM patients treated with daratumumab from September 2019 to November 2021 in West China Hospital were retrospectively enrolled, including 31 males and 21 females. The mean age of these patients at the first diagnosis of multiple myeloma was (58±10) years. According to the dosage of daratumumab, patients were divided into low dosage group (n=10) and high dosage group (n=42). Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse event rates were investigated. Univariate and multivariate analysis of potential factors were conducted. Results: Of the 52 patients, 8 received daratumumab monotherapy, 27 received daratumumab plus immuno-modulatory drug (IMiD) treatment, 4 received daratumumab plus proteosome inhibitor (PI) treatment, and 11 received daratumumab plus dexamethasone treatment. The diagnosis age of high dosage group patients was (57±9) years, which was significantly younger than that of low dosage group [(66±10) years] (P=0.009). The baseline creatinine level of high dosage group patients [M (Q1, Q3)] was 91 (68, 196) µmol/L, which was significantly higher than that of low dosage group [66 (51, 76) µmol/L] (P=0.021). There was no significant difference in other baseline clinical characteristics, previous treatment regimens, previous lines of treatment, and regimen and cycles of daratumumab between the high dosage group and low dosage group (all P>0.05). The ORR for the 52 patients was 71.2% (37/52). The ORR for daratumumab plus IMiD group was 81.5% (22/27), which was significantly higher than that in monotherapy or dexamethasone group [ORR: 52.6% (10/19), P=0.036). With a median follow-up [M (Q1, Q3)] of 7 (5, 26) months, the median PFS for overall cohort was 17 (95%CI: 9.6-24.4) months. The median PFS for daratumumab plus IMiD group was 26 (95%CI: 6.0-46.0) months, which was significantly better than that in monotherapy or dexamethasone group [12 (95%CI: 3.5-20.5) months] (HR=0.231, 95%CI: 0.075-0.715, P=0.011). Higher diagnosis age was the risk factor of progression (HR=1.085, 95%CI: 1.016-1.158, P=0.014), while more cycles of daratumumab treatment was the protective factor of progression (HR=0.669, 95%CI: 0.495-0.904, P=0.009). There was no significant influence of daratumumab dosage on progression (high dosage vs low dosage, HR=1.016, 95%CI: 0.221-4.668, P=0.984). The median OS for overall cohort was 26 (95%CI: 13.1-38.9) months. Higher serum calcium was the independent risk factor of death (HR=12.190, 95%CI: 1.170-127.048, P=0.037). There was no significant influence of daratumumab dosage on death (high dosage vs low dosage, HR=0.818, 95%CI: 0.171-3.917, P=0.802). Adverse events included infections (43.2%, 16/37), infusion-associated reactions (29.7%, 11/37), and thrombocytopenia (27.0%, 10/37). Conclusions: Daratumumab is effective to treat RRMM. The dosage of daratumumab has no significant influence on prognosis when used in combined treatment. The incidence of adverse events is relatively low, with a favorable safety profile.

[Cannabis use among the drug users with compulsory detained detoxification treatment in China].

OBJECTIVE: To explore the epidemic situation of cannabis use among drug users with compulsory detained detoxification treatment in China. METHODS: Using the data from the Drug Abuse Population Estimation in the Key Cities of the Ministry of Public Security, we analyzed the sociodemographic characteristics and substance use of cannabis abusers with compulsory detained detoxification treatment in 55 provincial capital cities and key cities of China. Chi-square test, Fisher exact test and Kruskal-Wallis rank sum test were used to compare the prevalence of cannabis, heroin, synthetic and mixed drug use among patients with detoxification treatment, as well as the differences in polydrug use and areas among cannabis users. RESULTS: In the study, 25 366 drug users with compulsory detained detoxification treatment were recruited, of whom 2.2% (546/25 366) used cannabis in the previous year before the treatment. The proportion of males was 83.5%, and the proportion of ethnic minorities was 41.0%. Those who received junior high school education or above accounted for 30.8%, and the unemployed accounted for 44.1%. The average age was (33.3±8.2) years, the average age of beginning drug use was (24.8±7.7) years, and the average duration between the first drug abuse and first detoxification treatment was (5.4±4.6) years. The prevalence of cannabis use was higher among those drug users who were 35-year-old and younger, ethnic minorities, employees and residents in Xinjiang. Of the cannabis users, 91.4% used polydrug, 13.6% combined with heroin alone, 42.1% combined with synthetic drugs alone and 35.7% combined with both of heroin and synthetic drugs. Of the cannabis users, 49.6% came from 3 regions: Xinjiang Uygur Autonomous Region, Jiangsu Province and Shanghai City. The cannabis users in Xinjiang had a high proportion of ethnic minorities who received junior high school education and below. Moreover, 79.6% of them combined cannabis use with heroin. The cannabis users in Jiangsu, Zhejiang and Shanghai areas had a higher proportion of ethnic Han who received better education (high school and above). Moreover, 92.7% of them combined cannabis use with methamphe-tamine. CONCLUSION: The prevalence of cannabis use among the population with compulsory detained detoxification treatment is higher than that among drug users under surveillance, but there are obvious regional cluster effect and high possibility of polydrug abuse. Thus, it's important to strengthen the monitoring of cannabis use, to increase the control of cannabis and to formulate China's anti-cannabis policy among different population.

Expression and characterization of calmodulin-activated (type I) adenylylcyclase.

A complementary DNA that encodes a bovine brain, calmodulin-sensitive (type I) adenylylcyclase has been inserted into the baculovirus genome under the control of the strong polyhedron promoter. Expression of the recombinant adenylylcyclase in Sf9 cells using recombinant baculovirus increases adenylylcyclase activity in cell membranes to 10-20 nmol.min-1.mg-1 (approximately 0.1% of membrane protein). The catalytic activity of the recombinant adenylylcyclase can be stimulated by Gs alpha, calmodulin, or forskolin, and it can be inhibited by adenosine analogs and by G protein beta gamma subunit. The specific activity of the purified recombinant protein approximates 5 mumol.min-1.mg-1. This is similar to that of the enzyme purified from bovine brain. Type I adenylylcyclase has a quasiduplicated structure. There are two membrane-spanning domains, each with six putative transmembrane helices, and there are two presumed nucleotide-binding domains that are about 55% similar to each other. No catalytic activity is detectable when each half of the adenylylcyclase molecule is expressed by itself. However, coexpression of the two halves results in considerable enzymatic activity. Interaction between the two halves of adenylylcyclase may be necessary for catalysis.