AIMTo ascertain the bioactivity and to analyse quantificationally the denervating action of botulinum toxin A (BTXA) in gel.

METHODS36 Sprague-Dawley rats were randomized into four groups. In group A - D, the gastrocnemius muscle of one leg was randomly selected to receive injection of BTXA solution 5U in 0.1 ml, BTXA gel 12.5U in 0.1 ml, BTXA gel 5U in 0.1 ml and BTXA gel 2U in 0.1 ml respectively, while the gastrocnemius muscle of other leg was injected with 0.1 ml of saline solution in group A and 0.1 ml of gel in group B to group D as control. Compound muscle action potential (CMAP) of both gastrocnemius muscles were measured and the amplitudes were recorded before injections, and 5 days, 2 weeks, 3 weeks, 1 month, 2 months and 3 months after the injections respectively.

RESULTSThe reduction of CMAP amplitude was significantly different at various time (P < 0.01), and CMAP amplitude decreased significantly after the treatment of BTXA (P < 0.01). The reduction of CMAP amplitude was significantly dif ferent in group A to I) (P < 0.01), and more reduction was found in group A and B (P < 0.01), and the reduction was higher in group C than in group D (P < 0.05). However, there were no significant differences in the reduction of CMAP amplitude between group A and group B.

CONCLUSIONBioactivity of BTXA in gel was showed and the denervating action of BTXA in gel was demonstrated in a dosage and time dependent manner.

Animals ; Botulinum Toxins, Type A ; administration & dosage ; Dosage Forms ; Female ; Gels ; Injections, Intramuscular ; Mice ; Muscle Denervation ; methods ; Muscle, Skeletal ; innervation ; Rats ; Rats, Sprague-Dawley ; Solutions

Objective:To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL).Methods:This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children′s Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors.Results:Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×10 9/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively ( χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant ( χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively ( χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%, χ2=4.13, P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%, χ2=4.06, P=0.044;(58.3±18.6)% vs. (85.7±3.2)%, χ2=9.44, P=0.002). Multivariate analysis showed that age ( OR=0.58, 95% CI 0.35-0.97) and white blood cell count at first diagnosis ( OR=0.43, 95% CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 ( OR=0.55,95% CI 0.31-0.97), ETV6-RUNX1 fusion gene ( OR=0.13,95% CI 0.03-0.54), MLL gene rearrangement ( OR=2.55,95% CI 1.18-5.53) and white blood cell count at initial diagnosis ( OR=0.52,95% CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions:The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

Objective:To analyze the clinically acceptable and reproducible bladder and rectum volumes of prostate cancer patients during radiotherapy under bladder and bowel preparation, aiming to provide quantitative indicators for bowel and bladder preparation before and after radiotherapy.Methods:Clinical data of 275 prostate cancer patients with strict bladder and bowel preparation and completion of whole course radical radiotherapy at Sun Yat-sen University Cancer Center from April 2015 to December 2020 were retrospectively analyzed. Patients were scanned with cone beam CT (CBCT) before each treatment and the setup error was recorded. Sixty-six patients were selected by simple random sampling and the bladder and rectum on daily CBCT was outlined using MIM software. The relationship between the ratio of daily bladder or rectum volume to the planned bladder or rectum volume (relative value of volume) and setup error was analyzed. Quantitative data were expressed as mean±SD. Normally distributed data were analyzed by paired t-test while non-normally distributed data were assessed by Kruskal-Wallis test.Results:The bladder and rectum volume on planning CT were (370.87±110.04) ml and (59.94±25.07) ml of 275 patients. The bladder and rectum volumes on planning CT were (357.51±107.38) ml and (65.28±35.37) ml respectively of the 66 selected patients with 1611 sets of CBCT images. And the bladder and rectum volumes on daily CBCT were (258.96±120.23) ml and (59.95 ± 30.40) ml. The bladder volume of patients was decreased by 3.59 ml per day on average during the treatment and 0.37 ml for the rectum volume. According to the bladder volume on planning CT, all patients were divided into three groups: <250 ml, 250-450 ml and >450 ml groups. The relative value of volume in the 250-450 ml group during the course of radiotherapy was the smallest. And the setup error in the superior and inferior (SI) direction was (0.28±0.24) cm and (0.19±0.17) cm in the left and right (LR) direction, significantly lower than those in the other two groups (both P≤0.027). According to the rectum volume on planning CT, all patients were divided into four groups: <50 ml, 50-<80 ml, 80-120 ml and >120 ml groups. The <50 ml group had the smallest relative value of volume during radiotherapy, and the setup error in the SI direction was (0.26±0.22) cm and (0.24±0.22) cm in the anterior and posterior (AP) direction, significantly smaller than those in the other groups (both P≤0.003). The setup errors in the SI, LR, AP directions of the enrolled 66 patients were (0.30±0.25) cm, (0.20±0.18) cm and (0.28±0.27) cm, respectively. Among them, the relative value of bladder volume in the AP direction was (0.73±0.37) in the setup error <0.3 cm group, which was statistically different from those in the setup error 0.3-0.5 cm and >0.5 cm groups (both P<0.05). Conclusion:Under the bladder and bowel preparation before planning CT, the appropriate bladder and rectum volumes are in the range of 250-450 ml and <50 ml, which yields higher reproducibility and smaller setup error.

Rheumatoid arthritis (RA), the most common inflammatory arthropathy word wild, is a systemic autoimmune disease that mainly affects the synovium of joints with a high disability rate. Metabolic mis-regulation has emerged as a fundamental pathogenesis of RA linked to immune cell dysfunction, while targeting immunometabolism provides a new and effective approach to regulate the immune responses and thus alleviate the symptom of RA. Recently, natural active compounds from traditional Chinese medicines (TCMs) have potential therapeutic effects on RA and regulating immunometabolism. In this review, in addition to updating the connection between cellular metabolism and cell function in immune cells of RA, we summarized that the anti-inflammatory mechanisms of the potential natural compounds from TCM by targeting metabolic reprogramming of immune cells, and discusses them as a rich resource for providing the new potential paradigm for the treatment of RA.

OBJECTIVE: To describe and analyze the status quo of cardiovascular clinical practice guidelines or expert consensuses including both Chinese medicine (CM) and integrative medicine, through systematic literatures searching and quality assessment. METHODS: Data bases including Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, Wanfang Data, China Science and Technology Journal Database were searched for published CM or integrative cardiovascular clinical practice guidelines or expert consensuses. The website www. medlive.cn was also retrieved as supplementary. The clinical practice evaluation tool AGREE II was used to assess the quality of included guidelines or consensuses. RESULTS: A total of 31 relevant clinical practice guidelines or expert consensuses were included, covering diagnosis, treatment, Chinese patent and patient fields. Common cardiovascular diseases like coronary heart diseases, heart failure and arrhythmia were also involved. Through analysis it was found that both the quantity and quality of included guidelines have been improved year by year. A total of 4 evidence-based clinical practice guideline has been found, one of which was a guideline project plan. Except that, the remaining 27 reports were all consensus-based guidelines. The scores of each field, from highest to lowest, were clarity of presentation (58%), scope and purpose (54%), stakeholder involvement (28%), rigor of development (21%), applicability (13%) and editorial independence (8%). CONCLUSIONS Although clinical practice guidelines in cardiovascular domain of Chinese have gained increasing concern, with both quantity and quality improved, there is still huge gap in methodology and reporting standards between CM guidelines and international ones. On the one hand, it is essential to improve and standardize the methodology of developing CM guidelines. On the other hands, the evaluation system of evidence and recommendation with CM characters should be developed urgently.