Recognition has been achieved in the molecular targeting of several key signaling transduction pathways governing cell survival and proliferation in chronic lymphocytic leukemia (CLL).A milestone in CLL treatment is reached.This review provides a brief summary of the 54th ASH annual meeting,focusing on recent advances in the preclinical and clinical investigation of promising target-directed therapeutic agents.

Objective:To analyze and the smile line of Zhuang-Chinese youths.Methods:1 00 Zhuang volunteers aged 1 8-25 years were recruited for this study.The faces were individually registered by digital videography.The length and thickness of upper lips and mandibular incisor crown height appearance at rest,smile and laugh were recorded.Statistical analysis was performed using Mann-Whitney-U Test and non-parametric analysis.Results:The upper lip in men was longer than that in women at rest(P<0.05 ).The upper lip length increased and thickness decreased at smile and laugh in all subjects,in men was longer and thicker than in women(P<0.05),but there was no significant difference of upper lip thickness at rest between sexes(P<0.05).The mandibular anterior teeth,gingival papilla of all subjects were appeared at smile and laugh,there was no significant difference between sexes(P<0.05). Gingiva appearance at smile was in less than 1 0%of the subjects.39%subjects had high smile line,46%had average smile line and 1 5% had low smile line.Conclusion:Most of the Zhuang youths have moderate smile line,less high smile line and least low smile line.

Objective To investigate the changes of cerebral blood flow and the level of brain injury in a rat model of deep hypothermia low flow(DHLF).Methods Twelve SD rats aged 3 weeks were randomly divided into sham group and model group.Regional cerebral blood flow(rCBF)of all rats was measured continuously during the operation by laser Doppler flowmetry,and the changes of rCBF were measured before temperature decreased,when the temperature decreased to(21.0±0.5)℃,0-5 minutes,25-30 minutes,55-60 minutes,115-120 minutes during DHLF and 0-5 minutes after DHLF operation.Another 60 SD rats aged 3 weeks were randomly divided into sham group and model group.Six rats of each group were sacrificed at 1,6,24,72 hours and 7 days after DHLF operation to detect the pathological changes of the brain and the neuronal apoptosis by HE staining and TUNEL assay.The neurological deficit score(NDS)was recorded at 24,72 hours and 7 days after operation for evaluating the neurologic functional outcome.ResultsWhen the temperature was decreased to(21.0±0.5)℃,the levels of rCBF of sham group and model group were significantly decreased to(41.1±4.2)% and(40.7±3.4)% of the baseline value,and the rCBF level of model group was further decreased to(15.7±3.5)% of the baseline value 0-15 minutes during DHLF(P ＜ 0.01),with no obvious changes in all the time intervals during DHLF.Compared with the sham group,the scores of NDS of model group were significant lower at 24 and 72 hours after operation(P ＜ 0.05 or 0.01).Besides,a significant pathological change of the brain tissue and a increased percentage of TUNEL-positive staining cells were observed in model group at 6,24,72 hours and 7 days after operation(P ＜ 0.01).Conclusions Rat model of DHLF is an ideal and reliable model of brain injury,for it is similar to DHLF procedure of clinical cardiac operation.

Objective To study the prognosis of infants with bronchiolitis by testing urine leukotriene E4 (LTE4) level and investigating atopy's influences. Methods Urine LTE4 was tested in 38 eases with mild bronchiolitis (47 in acute stage, 17 in convalescent stage), 9 severe bronchiolitis cases, 15 atopic cases, 25 control cases. Peripheral blood was used to determine eosinophils count (EC) in acute bronchiolitis cases. Results (1) The level of urine LTE4 is obviously higher in cases of acute group (62.11 ± 12.23 pmol/L) than that of control group (22.19±1.50 pmol/L) , and the convalescent group (34.86 ±5.75 pmol/L) (F = 132.42, P < 0.01) ;Urine LTE4 level of convalescent group is higher than that of the control group (P < 0.01). (2) Urine LTE4 level is significantly higher in severe group (98.04 ± 8.04 pmol/L) than that of mild group (59.16 ± 12.25 pmol/L) (t = 9.92, P < 0.01). (3) Urine LTE4 level of atopy positive (88.75 ± 10.45 pmol/L) infants with bronchiolitis is significantly higher than atopy negative infants (55.28 ± 11.44 pmol/L)(t = 8.63, P < 0.01). (4) There is no significant correlation between the levels of urine LTE4 and EC for acute bronchiolitis. Condusions The level of urine LTE4 in acute bronehiolitis patients increases and remains high in convalescent stage;Higher urine LTE4 level in severe bronchiolitis cases indicates that urine LTE4 level is related to the severity of the disease;cysteinylleukotrenes is an important mediator of inflammation that may influence the prognosis of atopy positive infants with bronchiolitis;EC is not a good index to present the airway inflammation of infants with bronehiolitis.

This study aimed to further enhance 2-keto-L-gulonic acid (2-KLG) production efficiency. A strategy for enhancing Ketogulonigenium vulgare growth and 2-KLG production by improving B. megaterium growth with sucrose was developed based on the time course of osmolality during 2-KLG industrial scale fermentation and effects of osmolality on cells growth and 2-KLG production. Results showed that the accumulation of 2-KLG and the feeding of alkaline matter led to an osmolality rise of 832 mOsmol/kg in the culture broth. High osmotic stress (1 250 mOsmol/kg) made the growth ofB. megaterium and K. vulgare decreased 15.4% and 31.7%, respectively, and consequently the titer and productivity of 2-KLG reduced 67.5% and 69.3%, respectively. When supplement sucrose under high osmotic condition (1 250 mOsmol/kg), B. megaterium growth was significantly improved, with the result that 2-KLG production was increased 87%. Furthermore, by applying this sucrose addition strategy further to batch fermentation in 3 L fermentor, the productivity of 2-KLG increased 10.4%, and the duration of fermentation declined 10.8%. The results presented here provide a potential strategy for enhancing the target metabolites produced by mixed strains at environmental stress.
Bacillus megaterium ; genetics ; growth & development ; metabolism ; Fermentation ; Industrial Microbiology ; Osmosis ; Rhodobacteraceae ; genetics ; growth & development ; metabolism ; Stress, Physiological ; Sucrose ; pharmacology ; Sugar Acids ; metabolism

The aim of this study was to improve the 2-keto-L-gulonic acid (2-KLG) production efficiency by Ketogulonicigenium vulgare and Bacillus megaterium by using multi-stage pH control strategy. The effect of pH on the cell growths and 2-KLG production showed that the optimum pH for K. vulgare and B. megaterium cell growth were 6.0 and 8.0, respectively, while the optimum pH for 2-KLG production was 7.0. Based on the above results, we developed a three-stage pH control strategy: the pH was kept at 8.0 during the first 8 h, then decreased to 6.0 for the following 12 h, and maintained at 7.0 to the end of fermentation. With this strategy, the titer, productivity of 2-KLG and L-sorbose consumption rate were achieved at 77.3 g/L, 1.38 g/(L x h) and 1.42 g/(L x h), respectively, which were 9.7%, 33.2% and 25.7% higher than the corresponding values of the single pH (pH 7.0) control model.
Bacillus megaterium ; growth & development ; metabolism ; Culture Media ; chemistry ; Fermentation ; Hydrogen-Ion Concentration ; Rhodobacteraceae ; growth & development ; metabolism ; Sorbose ; metabolism ; Sugar Acids ; metabolism

Objective:To explore the sequence of reduction and fixation in the treatment of middle and lower tibiofibular fractures on the same plane using tibial intramedullary nailing plus fibular plating.Methods:A retrospective analysis was performed of the 58 patients with middle and lower tibiofibular fractures on the same plane from January 2016 to December 2017. They were 38 males and 20 females, aged from 20 to 65 years (average, 40 years). The left side was affected in 30 cases and the right in 28. By the AO classification, 27 cases were type 42-A, 18 ones type 42-B and 13 ones type 42-C. Of them, 33 had the fibula reduced and fixated first (the fibular group) while 25 had the tibia reduced and fixated first (the tibial group). The 2 groups were compared in terms of operation time, rate of tibial closed reduction, rate of dynamization of intramedullary nails, fracture healing time and postoperative complications.Results:All the patients were followed up for 12 to 24 months (average, 17.2 months). The operation time in the fibular group was 96 minutes ± 15 minutes, significantly shorter than that in the tibial group (116 minutes ± 19 minutes)( P<0.05). The rate of tibial closed reduction was 84.8% (28/33) in the fibular group and 60.0%(15/25) in the tibial group, presenting a significant difference ( P<0.05). There were no significant differences between the 2 groups in the rate of dynamization of intramedullary nails, fracture healing time or postoperative complications ( P>0.05). Conclusions:Tibial intramedullary nailing plus fibular plate osteosynthesis is an effective treatment for the middle and lower tibiofibular fractures on the same plane. When the fracture line is not located in the narrow segment of the tibia, reduction and fixation of the fibula first is advantageous over reduction and fixation of the tibia first, because it can facilitate tibial reduction and nail placement and improve surgical efficiency without increasing the fracture healing time.

Objective:To explore the efficacy of small incision open reduction and internal fixation and arthroscopic high strength non-absorbable suture in the treatment of tibial avulsion fracture of anterior cruciate ligament (ACL).Methods:The clinical data of 72 patients with ACL tibial avulsion fracture treated in Shantou Central Hospital from April 2018 to April 2020 were analyzed retrospectively. The patients were randomly divided into control group ( n=36) and experimental group ( n=36). The control group was treated with small incision open reduction and internal fixation and the experimental group was treated with high intensity non-absorbable suture under arthroscopy. The general data, surgical indexes and postoperative adverse reactions of the two groups were compared, and the knee joint function indexes of the two groups before and after treatment were compared and evaluated by random walking model. The counting data were expressed by percentage, the comparison between groups was expressed by chi-square test, the measurement data was expressed by mean ±standard deviation, the independent t-test was used for inter-group comparison, and the paired t-test was used for intra-group comparison. Results:There was no significant difference in general information, intraoperative blood loss, preoperative Lysholm score, IKDC score, Tegner score, knee mobility, and bilateral tibial displacement distance between the two groups of patients ( P>0.05). In the experimental group, the operation time, hospitalization time, the first postoperative time to move to the ground, bone healing time, and the total incidence of adverse reactions were (68.41±7.65) min, (11.93±3.24) d, (6.37±1.85) d, (23.65± 2.28) weeks, 2.78% (1/36), the control group were (55.37±8.62) min, (13.45±2.96) d, (8.16±2.08) d, (25.79±2.46) weeks, 22.22% (8/36), the difference between the two groups was statistically significant ( P<0.05). The Lysholm score, IKDC score, Tegner score, range of motion of the knee joint, and the difference of bilateral tibial displacement distance after treatment in the experimental group were (85.27±5.28) points, (85.43±1.74) points, and (6.65±1.41) points, respectively. (108.45±5.79)°, (1.12±0.65) mm, the control group was (79.73±4.69) points, (80.37±1.59) points, (5.72±1.31) points, (97.58±5.42)°, (2.24±0.72) mm, the difference between the two groups was statistically significant ( P<0.05). Random walking model evaluation the improvement of knee joint function in the experimental group was significantly better than that in the control group. Conclusion:Arthroscopic treatment of ACL tibial avulsion fracture with high-intensity non-absorbable suture can significantly improve the knee joint function of patients with rapid recovery and high safety, so it has a broad prospect of clinical application.

Objective:To investigate the feasibility of reducing the radiation dose on coronary artery calcium score (CS) of virtual non-contrast (VNC) scanning in dual-layer spectral coronary CT angiography(CCTA).Methods:One hundred and twenty-two patients were examined on a dual-layer spectral detector CT scanner from March 2019 to August 2020. Volume CT dose index (CTDI vol), dose length product (DLP), effective dose ( E) were all evaluated for each patient. CS was calculated from both true non-contrast (TNC) and VNC images for left anterior descending (LAD), left circumflex (LCx), right coronary artery (RCA), and the total coronary artery (Total) by two radiologists independently. Pearson′s correlation coefficient was calculated for measuring the association between variables. The correction coefficients of each branch (λ LAD, λ LCx, and λ RCA) and the average correction coefficient (λ AVG) of the total coronary artery were obtained. The calibrated calcium score (CCS_VNC) was equal to λ multiplied by CS_VNC. The CS_TNC and CCS_VNC were compared using repeated oneway analysis of variance test. Correlation analyses for CS_TNC and CCS_VNC and agreement evaluation with Bland-Altman-Plots were performed. Results:The average effective doses in TNC, CCTA and total group were 0.69, 6.47 and 7.16 mSv, respectively. The effective dose was reduced by 10.6% and the scan time was reduced by 39% while using VNC images. There were significant differences among the CS_TNC and CS_VNC of LAD, LCx, RCA and Total ( t=6.75, 5.33, 4.99, 6.60, P< 0.05). Excellent correlations were observed between CS_VNC and CS_TNC ( R2 values were 0.929, 0.896, 0.958, and 0.918; λ values were 2.18, 1.18, 2.15, and 2.07, respectively). There were no significant statistically difference among the CS_TNC, CCS_VNC AVG, and CCS_VNC LAD/RCA of the LAD and RCA (all P> 0.05). The difference was statistically significant among the CS_TNC, CCS_VNC AVG, and CCS_VNC LCx of the LCx ( F=10.94, P<0.05). The paired comparison were performed in groups and the differences were statistically significant between the CS_TNC versus CCS_VNC AVGand CCS_VNC AVG versus CCS_VNC LCx ( t=3.31, 3.43, all P<0.05). There was no significant statistically difference between the CCS_VNC LCx and CCS_VNC AVG( P>0.05). Conclusions:It was feasible to accurately evaluate the CS_VNC from spectral data in comparison to TNC imaging, and to reduce the patient radiation dose and acquisition time.

The CRISPR/Cas9 gene editing system has been widely used in basic research, gene therapy and genetic engineering due to its high efficiency, fast speed and convenience. Meanwhile, the discovery of novel CRISPR/Cas systems in the microbial community also accelerated the emergence of novel gene editing tools. CRISPR/Cpf1 is the second type (V type) CRISPR system that can edit mammalian genome. Compared with the CRISPR/Cas9, CRISPR/Cpf1 can use 5'T-PAM rich region to increase the genome coverage, and has many advantages, such as sticky end of cleavage site and less homologous recombination repair. Here we constructed three CRISPR/Cpf1 (AsCpf1, FnCpf1 and LbCpf1) expression vectors in silkworm cells. We selected a highly conserved BmHSP60 gene and an ATPase family BmATAD3A gene to design the target gRNA, and constructed gHSP60-266 and gATAD3A-346 knockout vectors. The efficiency for editing the target genes BmATAD3A and BmHSP60 by AsCpf1, FnCpf1 and LbCpf1 were analyzed by T7E1 analysis and T-clone sequencing. Moreover, the effects of target gene knockout by different gene editing systems on the protein translation of BmHSP60 and BmATAD3A were analyzed by Western blotting. We demonstrate the CRISPR/Cpf1 gene editing system developed in this study could effectively edit the silkworm genome, thus providing a novel method for silkworm gene function research, genetic engineering and genetic breeding.
Animals ; Bombyx/metabolism* ; CRISPR-Cas Systems/genetics* ; Endonucleases/genetics* ; Gene Editing ; RNA, Guide/genetics*