Objective To analyze the clinical efficacy of Saccharomyces boulardii capsules combined with mesalazine enteric-coated in the treatment of patients with ulcerative colitis(UC)and its influence on intestinal microecology and mucosal inflammation.Methods Patients with UC were randomly divided into control group and treatment group.The control group took mesalazine enteric-coated(0.5 g,tid),while the treatment group was given Saccharomyces boulardii capsule orally(0.5 g,bid)on the basis of the control group,and both groups were treated for 2 months.The clinical efficacy,mucosal healing status(modified Mayo score,Geboes index score),intestinal mucosal inflammatory indicators and intestinal microecology were compared between groups of patients,and the safety evaluation was performed.Results 45 cases were included in control group and treatment group,respectively.After 2 months of treatment,the total effective rates of treatment in treatment group and control group were 86.67％(39 cases/45 cases)and 66.67％(30 cases/45 cases),the difference was statistically significant(P＜0.05).After treatment,the modified Mayo scores were(3.02±0.85)and(3.88±1.01)points,the Geboes index scores were(0.63±0.15)and(0.91±0.20)points,the levels of interleukin-6(IL-6)were(39.27±8.89)and(67.94±11.02)pg·mL-1,the levels of interleukin-10(IL-10)were(61.44±7.76)and(50.28±6.74)ng·L-1,the levels of interleukin-23(IL-23)were(452.19±80.01)and(514.68±95.93)ng·mL-1,the levels of tumor necrosis factor-α(TNF-α)were(30.93±4.68)and(46.75±8.31)ng·L-1,the Bifidobacteria counts were(10.49±1.87)and(9.57±1.73)lgCFU·g-1,the Lactobacillus counts were(9.43±1.66)and(7.94±1.39)lgCFU·g-1,the Colibacillus counts were(7.15±1.29)and(8.03±1.47)lgCFU·g-1,the Enterococci counts were(6.59±1.02)and(7.81±1.14)lgCFU·g-1,respectively(all P＜0.05).The adverse reactions in treatment group included nausea,the adverse drug reactions in control group included nausea and dizziness.The incidence rates of adverse drug reactions in treatment group and control group were 4.44％(2 cases/45 cases)and 4.44％(2 cases/45 cases),respectively(P＞0.05).Conclusion Saccharomyces boulardii capsule combined with mesalazine enteric-coated tablet has significant effect in the treatment of UC,which can effectively inhibit the intestinal mucosal inflammation,improve the intestinal microecology and promote the intestinal mucosal healing,and it has good safety.

Objective To investigate the effect of dihydromyricetin(DMY)on myocardial oxidative damage in exhaustive exercise mice.Methods C57BL/6 mice were divided into control group,model group,positive control group and low,medium and high dose experimental groups and with 10 mice in each group.Mice in control group and model group were intragastricated with distilled water;20,40 and 80 mg·kg-1 dihydromyricetin were given by gavage in low,medium and high dose experimental groups,while mice in positive control group were intragastricated with 100 mg·kg-1 Vitamin C once a day for 4 weeks.After administration,superoxide dismutase(SOD),malondialdehyde(MDA)and lactate dehydrogenase(LDH)were detected by the kit.The expression of nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)protein were detected by Western blot.Results SOD levels in control group,model group and low,medium,high dose experimental groups and positive control group were(57.81±6.92),(26.85±2.74),(33.68±4.52),(39.74±3.95),(48.97±4.26)and(39.22±3.54)U·mg-1;MDA were(4.72±0.36),(10.48±1.68),(8.75±0.82),(6.43±0.71),(5.11±0.48)and(6.36±0.64)nmol·mg-1;LDH were(268.71±23.94),(726.58±81.26),(621.32±47.59),(479.12±50.24),(337.91±34.99)and(486.15±50.98)U·L-1;Nrf2 protein expression were 0.75±0.06,0.19±0.02,0.30±0.04,0.47±0.05,0.63±0.06 and 0.49±0.06;the protein expression of HO-1 were 0.83±0.08,0.27±0.05,0.39±0.04,0.52±0.03,0.77±0.07 and 0.55±0.06,respectively.There were statistically significant differences between control group and model group(all P＜0.05);there were statistically significant differences in the above indexes between model group and positive control group,low dose experimental group,medium dose experimental group,high dose experimental group(all P＜0.05).Conclusion Dihydromyricetin can delay myocardial oxidative injury in exhaustive exercise mice,which may be related to Nrf2/HO-1 pathway.

Objective To investigate the effects of verbascoside on oxygen consumption and mitochondrial enzyme activities in skeletal muscle of rats with intense exercise.Methods Fifty SD rats were randomly divided into control group,model group,experimental-L,-M,-H groups.Exercise training was performed in all groups except the control group.The control group and model group were given 2 mL of 0.9％NaCl,the experimental-L,-M,-H groups was given 20,40,80 mg·kg-1·d-1 verbascoside.The activities of Na+/K+-ATP and Ca2+/Mg2+-ATP were detected by kit.Protein expressions of optic atrophy 1(Opa1),mitochondrial fusion(Mfn)1 and Mfn2 were detected by Western blot.Results The Na+/K+-ATP of experimental-L,-M,-H groups,model group and blank group were(2.74±0.44),(3.50±0.38),(4.39±0.41),(2.13±0.32)and(5.75±0.42)U·mg-1;Ca2+/Mg2+-ATP were(4.01±0.32),(4.82±0.79),(6.57±0.70),(3.51±0.35)and(8.92±1.14)U·mg-1;Opa-1 were 0.40±0.05,0.52±0.04,0.69±0.09,0.25±0.06 and 0.78±0.11;Mfn1 were 0.47±0.06,0.59±0.07,0.74±0.08,0.32±0.05 and 0.89±0.12;Mfn2 were 0.51±0.07,0.65±0.06,0.83±0.06,0.35±0.06 and 1.02±0.13,respectively.There was statistical significance between control group and model group(all P＜0.05);there were statistically significant differences in the above indexes between the experimental-L,-M,-H groups and the model group(all P＜0.05).Conclusion Verminoside can improve the oxygen consumption and mitochondrial enzyme activity of skeletal muscle and increase the antioxidant capacity of rats with intense exercise.

Objective To analyze the clinical efficacy of Saccharomyces boulardii capsules combined with mesalazine enteric-coated in the treatment of patients with ulcerative colitis(UC)and its influence on intestinal microecology and mucosal inflammation.Methods Patients with UC were randomly divided into control group and treatment group.The control group took mesalazine enteric-coated(0.5 g,tid),while the treatment group was given Saccharomyces boulardii capsule orally(0.5 g,bid)on the basis of the control group,and both groups were treated for 2 months.The clinical efficacy,mucosal healing status(modified Mayo score,Geboes index score),intestinal mucosal inflammatory indicators and intestinal microecology were compared between groups of patients,and the safety evaluation was performed.Results 45 cases were included in control group and treatment group,respectively.After 2 months of treatment,the total effective rates of treatment in treatment group and control group were 86.67％(39 cases/45 cases)and 66.67％(30 cases/45 cases),the difference was statistically significant(P＜0.05).After treatment,the modified Mayo scores were(3.02±0.85)and(3.88±1.01)points,the Geboes index scores were(0.63±0.15)and(0.91±0.20)points,the levels of interleukin-6(IL-6)were(39.27±8.89)and(67.94±11.02)pg·mL-1,the levels of interleukin-10(IL-10)were(61.44±7.76)and(50.28±6.74)ng·L-1,the levels of interleukin-23(IL-23)were(452.19±80.01)and(514.68±95.93)ng·mL-1,the levels of tumor necrosis factor-α(TNF-α)were(30.93±4.68)and(46.75±8.31)ng·L-1,the Bifidobacteria counts were(10.49±1.87)and(9.57±1.73)lgCFU·g-1,the Lactobacillus counts were(9.43±1.66)and(7.94±1.39)lgCFU·g-1,the Colibacillus counts were(7.15±1.29)and(8.03±1.47)lgCFU·g-1,the Enterococci counts were(6.59±1.02)and(7.81±1.14)lgCFU·g-1,respectively(all P＜0.05).The adverse reactions in treatment group included nausea,the adverse drug reactions in control group included nausea and dizziness.The incidence rates of adverse drug reactions in treatment group and control group were 4.44％(2 cases/45 cases)and 4.44％(2 cases/45 cases),respectively(P＞0.05).Conclusion Saccharomyces boulardii capsule combined with mesalazine enteric-coated tablet has significant effect in the treatment of UC,which can effectively inhibit the intestinal mucosal inflammation,improve the intestinal microecology and promote the intestinal mucosal healing,and it has good safety.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVETo investigate the effect of adenosine A2A receptor knockout (A(2A)RKO) on relationship between continuous activation of phospho-c-Jun N-terminal kinase (P-JNK) and expression of nerve cell apoptosis in hippocampus CA1 domain of newborn mice after hypoxia/ischemia brain damage(HIBD) and its potential mechanism.

METHODSA(2A)RKO mice and adenosine A2A receptor wildtype (A(2A)RWT) littermates (n = 80) were divided into Sham operation group (S) and model group (M), 1, 3 and 7 day after HIBD, totally 8 groups. HIBD was developed with 7 day-old neonatal mice according classical Rice-Vannucci method. It was tested the effect of A(2A)RKO on short-term neurofunctional outcomes consisted of three developmental reflexes (righting, geotaxis and cliff aversion), the changes of brain pathology with hematoxylin-eosin (HE) staining and Nissl staining, the expressions of nerve cell apoptosis with terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling(TUNEL) staining and P-JNK were observed by immunohistochemistry.

RESULTSThe neurological behavior injuries and brain histopathological damages and nerve apoptosis cells were aggravated in A(2A)RKO newborn mice after HIBD. The positive expressions of P-JNK were significantly higher in the ischemic hippocampus CA1 domain after HIBD than ones in group S respectively (P < 0.01), reaching to peak at 1 day and then began gradually decreasing. P-JNK expression in model knockout(MKO) at 1, 3 and 7 day increased greatly compared to those in the previous time point of corresponding model wildtype (MWT) (P < 0.01, P < 0.05, P > 0.05); there was a positive correlation between the expressions of P-JNK and nerve cell apoptosis after HIBD in newborn mice(r = 0.837, P < 0.01).

CONCLUSIONEarly continuous activation of P-JNK might be involved in the aggravated nerve apoptosis cells and brain damage induced by A(2A) RKO newborn mice after HIBD.

Animals ; Animals, Newborn ; Apoptosis ; Hypoxia-Ischemia, Brain ; metabolism ; pathology ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Mice ; Mice, Knockout ; Neurons ; drug effects ; metabolism ; pathology ; Receptor, Adenosine A2A ; genetics