Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia / 中国结合医学杂志

OBJECTIVE@#To explore the effect of Kuanxiong Aerosol (KXA) on isoproterenol (ISO)-induced myocardial injury in rat models.@*METHODS@#Totally 24 rats were radomly divided into control, ISO, KXA low-dose and high-dose groups according to the randomized block design method, and were administered by intragastric administration for 10 consecutive days, and on the 9th and 10th days, rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA. In addition, the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test. The influence of KXA on the expression of calcium-CaM-dependent protein kinase II (CaMK II)/extracellular regulated protein kinases (ERK) signaling pathway has also been tested.@*RESULTS@#KXA significantly reduced the ISO-induced increase in ST-segment, interventricular septal thickness, cardiac mass index and cardiac tissue pathological changes in rats. Moreover, the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine (NE) or potassium chloride (KCl) was increased after KXA treatment in an endothelium-independent manner, and was attenuated by preincubation with verapamil, but not with tetraethylammonium chloride, 4-aminopyridine, glibenclamide, or barium chloride. KXA pretreatment attenuated vasoconstriction induced by CaCl2 in Ca2+-free solutions containing K+ or NE. In addition, KXA pretreatment inhibited accumulation of Ca2+ in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK II and p-ERK levels.@*CONCLUSION@#KXA may inhibit influx and release of calcium and activate the CaMK II/ERK signaling pathway to produce vasodilatory effects, thereby improving myocardial injury.

Efficacy of Chimeric Antigen Receptor T Cell in the Treatment of Refractory/Recurrent B Acute Lymphocytic Leukemia in Children / 中国实验血液学杂志

OBJECTIVE@#To observe the efficacy of chimeric antigen receptor T cell (CAR-T) in the treatment of children with refractory/recurrent B acute lymphocytic leukemia (B-ALL).@*METHODS@#Thirty-two patients with r/r B-ALL were treated by CAR-T, the recurrence and death respectively were the end point events to evaluate the efficacy and safety of CAR-T.@*RESULTS@#The median age of the patients was 7.5 (2-17.5) years old; 40 times CAR-T were received in all patients and the median number of CAR-T was 0.9×107/kg; efficacy evaluation showed that 2 cases died before the first evaluation. Thirty patients showed that 3, 6, and 9-moth RFS was (96.3±3.6)%, (81.4±8.6)% and (65.3±12.5)%, respectively, while 3, 6, and 9-month OS was all 100%, and 12, 24-month OS was (94.7±5.1)% and (76±12.8)%. BM blasts≥36% before reinfusion and ferritin peak≥2 500 ng/ml within two weeks of CAR-T cell reinfusion were associated with recurrence. Adverse reactions mainly included cytokine release syndrome (CRS) and CART-cell-related encephalopathy syndrome (CRES), CRS appeared in 26 patients within a week of CAR-T cell reinfusion. CRES reaction was detected in 12 patients. Eighteen patients received intravenous drip of tocilizumab, among them, 12 combined with glucocorticoid. CRS and CRES reactions were relieved within one week after treatment. Hormone dosage was related to the duration of remission in patients, and the cumulative dose of methylprednisolone≥8 mg/kg showed a poor prognosis.@*CONCLUSION@#CAR-T is a safe and effective treatment for r/r B-ALL, most CRS and CRES reactions are reversible. BM blasts ≥36% before reinfusion and cumulative dose of methylprednisolone ≥8 mg/kg after reinfusion both affect the therapeutic effect. Ferritin≥2 500 ng/ml within two weeks after reinfusion is related to disease recurrence and is an independent prognostic risk factor.

The impact of obstructive sleep apnea hypopnea syndrome on the perioperative and long-term outcome in patients with Stanford type A aortic dissection / 中华耳鼻咽喉头颈外科杂志

Objective: To confirm the impact of obstructive sleep apnea hypopnea syndrome (OSAHS) on perioperative and long-term outcome in patients with Stanford type A aortic dissection. Methods: From June 2010 to July 2017, the clinical data of 91 patients with Stanford type A aortic dissection were analyzed. Among them, 51 patients with OSAHS were included in the study group and 40 patients without OSAHS were included in the control group. After 36 months follow-up, all-cause death was regarded as the end event. The clinical baseline data, perioperative period and 36 months survival rate of the two groups were compared. Kanplan-Meier method was used to describe the 36 month survival curve of the two groups. Cox proportional risk model was used to evaluate the risk ratio (HR) and 95%CI of 36 month survival rate. Results: The mortality rate during hospitalization was 5.9% (3 cases) in the study group and 5.0% (2 cases) in the control group, and the difference was not statistically significant (χ~2=0.03, P>0.05). The actual follow-up was (36.2±1.5) months, 88 cases were followed up and 3 cases were lost. The all cause mortality rate of 36 months was 27.5% (14/51)in the study group and 10.0%(4/40) in the control group, the difference was statistically significant (χ~2=4.30, P<0.05).By Cox proportional risk model analysis, 36 months after operation, the study group was compared with the control group after adjusting for age, male, bicuspid of aortic valve, chronic obstructive pulmonary disease, anemia, preoperative pericardial tamponade, postoperative organ dysfunction, preoperative LVEF, emergency operation, Sun's operation, coronary artery bypass grafting, hypertension, cardiac arrhythmia, and advanced avulsion of distal aortic dissection The survival rate was lower, the difference was statistically significant (P<0.05).In addition to OSAHS, coronary artery bypass grafting and preoperative pericardial tamponade were also risk factors for the increase of 36 month mortality rate (HR=11.28,95%CI: 1.98-46.25, P=0.009; HR=9.08, 95%CI: 2.22-41.3, P=0.032). Conclusions: There was no significant difference in mortality during hospitalization in patients with Stanford A aortic dissection combined with OSAHS. The survival rate of 36 months after operation was lower than that of the control group.

Role of MiR-20a-3p in Axonal Repair in Rats with Spinal Cord Injury / 中国康复理论与实践

@#Objective:To study the molecular biology mechanisms of Wistar rats after spinal cord injury, and find out key microRNAs. Methods:A total of 15 Wistar rats were divided into control group (<italic>n</italic> = 3) and spinal cord injury group (<italic>n</italic> = 12). The latter group was divided into four hours, three days, seven days and 14 days subgroups, with three rats in each subgroup. Microarray 3.0 was used to investigate microRNA expression profiles of Wistar rats with spinal cord injury. Bioinformatics was used to predict microRNAs playing key regulatory roles, and to predict target genes. Reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) was applied to detect the expression of miR-20a-3p. Western blotting was employed to detect the signal transducer and activator of transcription (STAT) 3 level. The correlation between target protein and microRNA expression trend in each group was analyzed. The key microRNA was inhibited in the neurons. The relationship between target protein expression and axon growth was observed with immunofluorescence. Results:In the rats with spinal cord injury, totally 658 microRNAs had changed at least once. In all the altered microRNAs, miR-20a-3p was upregulated obviously. It predicted that the target gene of miR-20a-3p was STAT3 via application of bioinformatics analysis. The expression trend of STAT 3 and miR-20a-3p in spinal cord was opposite. After the inhibition of miR-20a-3p, the expression of STAT3 in neurons was unregulated and axonal growth was extended. Conclusion:The upregulation of miR-20a-3p leads to downregulation of STAT3, and miR-20a-3p is one of the key targets in the treatment of spinal cord injury.

Effect and mechanism of xanthan gum on osteoarthritis caused by anterior cruciate ligament transection / 药学学报

The study is designed to evaluate the protective effect of xanthan gum (XG) injection on cartilage injury in the rabbit osteoarthritis (OA) model induced by anterior cruciate ligament transection (ACLT), and to explore the effect of XG on the expression of caspase-3 and Bax protein in OA cartilage. Sixty male New Zealand white rabbits were randomly divided into 6 groups (n=10) according to random number table method, and one group was selected randomly as the normal control group (control) while the other 5 groups of right knee were used to establish the OA model with ACLT, which were then divided into model group (model), XG-0.6 mg·kg-1, XG-1.2 mg·kg-1, XG-2.4 mg·kg-1 treatment group and sodium hyaluronate (SH-1.2 mg·kg-1) treatment group according to drug intervention. The knee joint temperature and knee joint width of each group were measured in the course of treatment. After treatment, the macroscopic morphology of rabbit joints in each group was observed. The pathological morphology of articular cartilage of rabbits in each group was observed using HE staining. The expression of Bax and cleaved caspase-3 in the cartilage of rabbits were detected by Western blot. The result shows that XG inhibited the increase in knee joint temperature and knee width caused by OA in a dose-dependent manner. XG improved the morphological abnormalities and tissue injuries of the femoral condyle and tibial plateau caused by OA. Western blot result shows that, compared with the control group, the levels of Bax and cleaved caspase-3 in knee cartilage cells of model group and XG-0.6 mg·kg-1 group were significantly increased (P-1 group (P>0.05). These two groups are significantly higher than those of XG-1.2 mg·kg-1 and XG-2.4 mg·kg-1 (P-1 and XG-1.2 mg·kg-1 group (P>0.05). The level of Bax in knee cartilage in XG-2.4 mg·kg-1 group was lower than that of XG-1.2 mg·kg-1 group (P<0.05). In conclusion, XG effectively protected cartilage damage in OA, and inhibited the expression of Bax and caspase-3 protein in OA cartilage.

Application of two kinds of mesoporous silica for preparation of nimodipine solid dispersion / 中国药学杂志

OBJECTIVE: To prepare solid dispersion of mesoporous silica- nimodipine (NMP) in hope of improving its dissolution rate and bioavailability.