To evaluate the clinical safety of four CD19-targeted and two BCMA-targeted chimeric antigen receptor T-cell (CAR-T) therapies.

To provide a theoretical basis for different drug decision-making scenarios by conducting a comprehensive clinical evaluation of nusinersen.

Objective: To explore the characteristics of overweight children s attention bias to food cues, so as to provide a theoretical basis for the behavior and life intervention of overweight children. Methods: From September to October 2017, 28 normal weight children and 28 overweight children in grades 3 to 4 of a primary school in Shenyang were screened by body mass index (BMI). The point detection paradigm was used to evaluate the attention bias of overweight children to food cues. Results: There was no significant difference between overweight children and control children in the score of attention bias to food cues [ F (1,52)=0.01, P> 0.05 , ηp 2 <0.01]; there was significant difference between overweight children and normal weight children in the score of facilitated attention to food cues[ F (1,52)=5.94, P<0.05, ηp 2 =0.10], normal weight children had higher score of facilitated attention to food cues than that of overweight children; there was significant difference between overweight children and normal weight children in the score of difficulty in disengaging to food cues[ F (1,52)=7.74, P<0.05, ηp 2 =0.13], overweight children had higher score of difficulty in disengaging to food cues than that of normal weight children. Conclusion Compared with normal weight children, overweight children didn t have higher attention bias to food cues; in the specific indicators of attention bias to food cues, normal weight children are more alert to food cues, while overweight children are more difficult to remove attention from food cues.

OBJECTIVE To explore the improvement effect and potential mechanism of Baicao fuyanqing suppository on bacterial vaginitis （BV） in rats. METHODS The female SD rats were randomly divided into normal group， model group， metronidazole group （positive control， 0.03 g/kg）， Baicao fuyanqing suppository low-dose， medium-dose and high-dose groups （0.18， 0.36， 0.72 g/kg）， with 8 rats in each group. Except for the normal group， the rats in other groups were injected subcutaneously with 0.2 g of Estradiol benzoate injection+20 μL of Escherichia coli suspension （2×108～3×108 cfu/mL） through the vaginal opening to establish the BV rat model. Administration groups were given relevant medicine vaginally， while the normal group and the model group were given normal saline， once a day， for 6 consecutive days. Twenty-four hours after the last administration， the vaginal appearance score and vaginal pH were measured for each group of rats. The levels of cytokines [interleukin-1β （IL-1β）， IL-2， IL-13， immunoglobulin A （IgA）] in vaginal lavage fluid were determined. The morphology of the uterus and accessories， and pathological changes in the vaginal tissue were observed. The expressions of Toll-like receptor 2 （TLR2）， TLR4 and nuclear factor-κB （NF-κB） in vaginal tissues were determined. RESULTS Compared with the normal group， the uterus edema， the irregular shape of uterus and accessories， the vaginal mucosa hyperplasia， and the massive desquamation of epithelial cells were observed in the model group， complicating with massive infiltration of inflammatory cells； vaginal opening redness and swelling score and secretion score， vaginal pH， the levels of proinflammatory cytokine IL-1β and IL-2， the protein expressions of TLR2， TLR4 and NF- κB were all increased or up-regulated， while the levels of IgA and anti-inflammatory cytokine IL-13 decreased significantly （P＜0.05 or P＜0.01）. Compared with the model group， varying cn degrees of improvement in uterine and accessories， and vaginal tissue lesions in rats were observed in administration groups， and most of the quantitative indicators mentioned above showed significant improvement （P＜0.05 or P＜0.01）. CONCLUSIONS Baicao fuyanqing suppository has a certain improvement effect on inflammatory symptoms in BV rats， and its mechanism may be related to the inhibition of the TLR/NF-κB signaling pathway.

Objective:This study aims to explore the effect of propranolol combined with memory retrieval reconsolidation procedure on alcohol craving.Methods:A total of 54 patients with alcohol dependence who met the diagnostic criteria for alcohol dependence in DSM-Ⅳ were enrolled. The patients were randomly located into the alcohol retrieval-propranolol group (study group, n=28) and the alcohol retrieval-placebo group (control group, n=26) using the random number table. The study group used propranolol combined with a memory retrieval reconsolidation procedure, while the control group used a placebo combined with a memory retrieval reconsolidation procedure. The Visual Analog Scale (VAS) was used to evaluate the degree of alcohol craving induced by images such as wine bottle, pouring wine, and drinking (alcohol-related cue images, previous cue images) and neutral images (new cue) at stages of baseline measures, relevance learning, and memory test. The systolic blood pressure, diastolic blood pressure, and heart rate were applied to evaluate cue responsiveness. Repeated measures analysis of variance was used to compare the craving degree, systolic blood pressure, diastolic blood pressure, and heart rate between the two groups. The correlation between cue responsiveness and craving degree was analyzed. Results:Relevance learning stage: Compared with before learning, the levels of systolic blood pressure, diastolic blood pressure, and heart rate of the two groups increased in varying degrees after learning conditional stimulation-relevance learning+(CS+, namely neutral images paired learning with alcohol) ( F=52.79, 42.44, 49.53, P<0.05). Compared with the baseline measures, the VAS of neutral images in relevancy learning increased ( F=99.88, 68.69, both P<0.01). Memory test stage: (1) Compared with the control group, the VAS scores of cravings induced by wine bottles, pouring wine, drinking images, and neutral images were lower in the study group ( F=7.38, 13.27, 11.34, 4.62, P<0.05). Compared with the VAS scores of cravings induced by wine bottles, pouring wine, drinking images, and neutral images in the relevance learning stage, the VAS scores of the study group in the memory test stage were significantly lower ( F=43.89, 23.53, 15.93, 31.01, P<0.05). For the control group, VAS scores induced by pouring wine and drinking images were significantly increased ( F=13.40, 63.65, P<0.05). (2) After the memory test stage, compared with the control group, the levels of diastolic blood pressure and heart rate in the study group decreased ( F=20.99, 15.42, P<0.05). Compared with before the test, the levels of diastolic blood pressure and heart rate in the study group decreased after the test ( F=4.11, 8.05, P<0.05), while those in the control group increased ( F=81.86, 41.13, P<0.05). (3) The difference in diastolic blood pressure before and after the memory test stage was positively correlated with the difference in neutral VAS score between the memory test and association learning ( r=0.394, P=0.038). Heart rate difference before and after the memory test stage positively correlated with the VAS score difference between the memory test and associated learning drinking images ( r=0.389, P=0.041). Conclusion:Propranolol combined with memory retrieval reconsolidation procedure can reduce alcohol cravings induced by previous and new cues in patients with alcohol dependence.

Objective:This study aims to explore the effect of propranolol combined with memory retrieval reconsolidation procedure on alcohol craving.Methods:A total of 54 patients with alcohol dependence who met the diagnostic criteria for alcohol dependence in DSM-Ⅳ were enrolled. The patients were randomly located into the alcohol retrieval-propranolol group (study group, n=28) and the alcohol retrieval-placebo group (control group, n=26) using the random number table. The study group used propranolol combined with a memory retrieval reconsolidation procedure, while the control group used a placebo combined with a memory retrieval reconsolidation procedure. The Visual Analog Scale (VAS) was used to evaluate the degree of alcohol craving induced by images such as wine bottle, pouring wine, and drinking (alcohol-related cue images, previous cue images) and neutral images (new cue) at stages of baseline measures, relevance learning, and memory test. The systolic blood pressure, diastolic blood pressure, and heart rate were applied to evaluate cue responsiveness. Repeated measures analysis of variance was used to compare the craving degree, systolic blood pressure, diastolic blood pressure, and heart rate between the two groups. The correlation between cue responsiveness and craving degree was analyzed. Results:Relevance learning stage: Compared with before learning, the levels of systolic blood pressure, diastolic blood pressure, and heart rate of the two groups increased in varying degrees after learning conditional stimulation-relevance learning+(CS+, namely neutral images paired learning with alcohol) ( F=52.79, 42.44, 49.53, P<0.05). Compared with the baseline measures, the VAS of neutral images in relevancy learning increased ( F=99.88, 68.69, both P<0.01). Memory test stage: (1) Compared with the control group, the VAS scores of cravings induced by wine bottles, pouring wine, drinking images, and neutral images were lower in the study group ( F=7.38, 13.27, 11.34, 4.62, P<0.05). Compared with the VAS scores of cravings induced by wine bottles, pouring wine, drinking images, and neutral images in the relevance learning stage, the VAS scores of the study group in the memory test stage were significantly lower ( F=43.89, 23.53, 15.93, 31.01, P<0.05). For the control group, VAS scores induced by pouring wine and drinking images were significantly increased ( F=13.40, 63.65, P<0.05). (2) After the memory test stage, compared with the control group, the levels of diastolic blood pressure and heart rate in the study group decreased ( F=20.99, 15.42, P<0.05). Compared with before the test, the levels of diastolic blood pressure and heart rate in the study group decreased after the test ( F=4.11, 8.05, P<0.05), while those in the control group increased ( F=81.86, 41.13, P<0.05). (3) The difference in diastolic blood pressure before and after the memory test stage was positively correlated with the difference in neutral VAS score between the memory test and association learning ( r=0.394, P=0.038). Heart rate difference before and after the memory test stage positively correlated with the VAS score difference between the memory test and associated learning drinking images ( r=0.389, P=0.041). Conclusion:Propranolol combined with memory retrieval reconsolidation procedure can reduce alcohol cravings induced by previous and new cues in patients with alcohol dependence.

RNA viruses are critically dependent upon virally encoded proteases to cleave the viral polyproteins into functional proteins. Many of these proteases exhibit a similar fold and contain an essential catalytic cysteine, offering the opportunity to inhibit these enzymes with electrophilic small molecules. Here we describe the successful application of quantitative irreversible tethering (qIT) to identify acrylamide fragments that target the active site cysteine of the 3C protease (3C^pro) of Enterovirus 71, the causative agent of hand, foot and mouth disease in humans, altering the substrate binding region. Further, we re-purpose these hits towards the main protease (M^pro) of SARS-CoV-2 which shares the 3C-like fold and a similar active site. The hit fragments covalently link to the catalytic cysteine of M^pro to inhibit its activity. We demonstrate that targeting the active site cysteine of M^pro can have profound allosteric effects, distorting secondary structures to disrupt the active dimeric unit.

Objective: To explore the effect of group cognitive behavioral therapy (GCBT) on cognitive control among college students with high obsessive compulsive traits, to provide basic information for the psychological counseling intervention for college students. Methods: From March to April 2019, 687 students were conveniently selected from 2 universities in Hefei. According to the inclusion and exclusion criteria, 58 students with high obsessive traits were selected and divided into experimental group ( n =29) and control group ( n =29) by random number table method. The experimental group received cognitive behavioral group counseling for 4 weeks (1.5 h each time, twice a week), while the control group receive no intervention. The Obsessive Compulsive Inventory Revised (OCI-R), Stroop Color Word Test (SCWT), Digital Span Test (DST), and Wisconsin Card Sorting Test (WSCT) were used to assess in two groups at baseline and 4 weeks later. Results: After 4 weeks, the scores of OCI-R in the GCBT group (10.28±7.22) was lower than that of in the control group (15.90±10.20) ( t=2.42, P<0.05). Before and after intervention, compared with the control group [(21.89±6.63, 20.52±7.37)s, (8.62±4.43, 8.04±4.84)s] in Stroop C and Stroop interfere effects (SIE), the GCBT group [(22.14±4.92, 16.81±3.43)s, (8.36±3.87, 4.82±1.86)s], the interaction of time group was statistically significant ( F =14.60, 10.54, P <0.05). Compared with the control group (6.21±1.35, 6.55±1.45)times, the scores of DST reverse in the GCBT group (6.31±1.44, 7.24±1.38) times were statistically significant ( F=3.96, P <0.05). Conclusion It suggests that cognitive behavioral group counseling can improve the inhibitory control and working memory of college students with high obsessive compulsive traits, but does not change the cognitive flexibility.

OBJECTIVE To analyze quality maker （Q-marker） of Ka nggongyan soft capsule （KSC）. METHODS The fingerprints of 20 batches of KSC were established by ultra high performance liquid chromatography （UPLC）method. Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition）were used to evaluate the similarity and confirm common peaks. The contents of norisoboldine ，leonurine hydrochloride ，forsythoside B ，acteoside，poliumoside and isoacteoside were determined by the same UPLC method. Targets and pathways related to KSC in the treatment of cervicitis were screened and analyzed by network pharmacology and molecular docking method to construct a “component-target-pathway”network，and analyze its potential Q-marker. RESULTS Twelve common peaks were identified in the fingerprints of 20 batches of KSC ，and the similarity was greater than 0.99. Six common peaks were identified ，including norisoboldine ，leonurine hydrochloride ，forsythoside B，acteoside，poliumoside and isoacteoside. The contents of the above 6 components were 1.336-1.774，0.093-0.143，4.970-5.888， 0.505-0.623，5.206-6.226 and 0.785-0.895 mg/g，respectively. By network pharmacology analysis ，14 key targets and 94 pathways were obtained ，and their binding energies to the core targets （protein kinase B 1，tumor necrosis factor ）were all less than －6.4 kJ/cal. CONCLUSIONS Six components such as norisoboldine and leonurine hydrochloride are potential Q-marker of KSC.