Background: and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

Compounds(1-6) were isolated and identified from 90% ethanol extract of the stems and leaves of Cassia occidentalis through column chromatography with silica gel, ODS, and Sephadex LH-20. These compounds were identified as 7-hydroxy-5-(3-hydroxy-2-oxopropyl)-2-methyl-4H-chromen-4-one(1), saccharonol A(2), S-6-hydroxymullein(3), 2-methyl-5-acetonyl-7-hydroxy-chromone(4), 2-(2'-hydroxypropyl)-5-methyl-7-hydroxychromone(5) and 7,4'-dihydroxyflavone(6) based on their physicochemical and spectroscopic data. Among them, compound 1 was a new compound, and all the compounds were isolated from this plant for the first time. DPPH method was employed to determine the antioxidant activities of these compounds in vitro. Six compounds exhibited weak antioxidant activities.
Chromones ; Plant Leaves ; Senna Plant ; Spectrum Analysis

Objective: To investigate the safety and short-term efficacy of apatinib combined with oxaliplatin and S-1 in the conversion treatment for gastric cancer with different types of peritoneal metastasis. Methods: A prospective study "one arm exploratory clinical study of conversion therapy of apatinib with S-1 and oxaliplatin in the treatment of advanced gastric cancer" (clinical registration ChiCTR-ONC-17010430) from medical record database was retrospectively analyzed. Patients aged 18-70 years with gastric cancer peritoneal metastasis confirmed by histology and laparoscopic exploration, and had not receive radiotherapy, chemotherapy, targeted therapy or immunotherapy before were enrolled. Before operation, the patients received 6 cycles of S-1 (80-120 mg/d, d1-d14) and oxaliplatin (130 mg/m(2), d1), and 5 cycles of apatinib (500 mg/d, d1-d21) conversion regimen. Three weeks after chemotherapy, whether the operation was performed or not depending on re-evaluation and patient preference. The main outcome were adverse reactions, and the secondary outcome were objective remission rate (ORR), disease control rate (DCR), and overall survival (OS) rate. The follow-up period was up to May 2020. Results: A total of 27 patients with gastric cancer peritoneal metastasis were enrolled in this study. There were 13 males and 14 females, with a median age of 58 (30-68) years old. There were 9 cases of P1a, 5 cases of P1b, and 13 cases of P1c. There were 14 cases with 1-5 scores of PCI (peritoneal cancer index), and 13 cases with 6 scores or above. The incidence of adverse reactions was 100%. The most common adverse reactions were hematological events including leucopenia (70.4%, 19/27) and granulocytopenia (74.1%, 20/27). Non-hematological adverse events included fatigue (51.9%, 14/27) and oral mucositis (37.0%, 10/27). One patient was withdrawn due to grade 4 thrombocytopenia. Among 26 patients with feasible efficacy evaluation, 18 (69.2%) achieved partial remission, 3 (11.5%) achieved stable disease, and 5 (19.2%) disease progression. The objective remission rate was 69.2% (18/26) and the disease control rate was 80.8% (21/26). Fourteen patients underwent surgery, including 6 patients undergoing R0 resection with the R0 resection rate of 42.9% (6/14). The postoperative pathological response rate was 64.3% (9/14). The follow-up time was 12-40 months, and the follow-up rate was 100%. The 1-year OS rate was 65.2% and the survival time was (14.0±1.7) months. The 1-year OS rates of P1a/P1b group and P1c group were 81.8% and 42.0% respectively, whose difference was statistically significant (P=0.041). The 1-year OS rates of PCI 1-5 group and PCI ≥6 group were 67.3% and 38.5% respectively, whose difference was statistically significant (P=0.022). Conclusion: In the conversion treatment of gastric cancer peritoneal metastasis, the safety of apatinib combined with oxaliplatin and S-1 is acceptable, and this regimen shows a good short-term survival efficacy in patients with P1a/P1b and PCI of 1-5.
Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Humans ; Male ; Middle Aged ; Oxaliplatin ; Percutaneous Coronary Intervention ; Peritoneal Neoplasms/drug therapy* ; Prospective Studies ; Pyridines ; Retrospective Studies ; Stomach Neoplasms/drug therapy*

Aged ; Cognitive Dysfunction/epidemiology* ; Cross-Sectional Studies ; Geriatric Assessment ; Humans ; Independent Living ; Sarcopenia/epidemiology*

OBJECTIVE: To investigate the expression level of miR-181b in CD19+ B lymphocytes of patients with chronic lymphocytic leukemia (CLL), to analyze the relationship between its expression and the prognosis of CLL patients, and to predict the potential target gene of miR-181b in CLL by using bioinformatics. METHODS: Eight-four patients with CLL treated in People's Hospital of Xinjiang Uygur Autonomous Region from June 2013 to June 2018 were selected. and 20 healthy people were selected as control group. RNA was extracted from CD19+B lymphocytes of peripheral blood by magnetic bead sorting, the expression level of miR-181b was detected, and it's expression differences in different IPI groups were analyzed. The correlation between the expression level of miR-181b and PFS of CLL patients also was analyzed. miR-181b target genes were predicted by online database and literatures, and gene annotation analysis and relevant signal pathway analysis were performed for candidate target genes. RESULTS: The expression level of miR-181b in CLL patients was significantly lower than that in control group (P＜0.01); The expression level of miR-181b in the low-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no statistical difference between low-risk group and medium-risk group (P=1.00). The expression level of miR-181b in medium-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no difference between high-risk group and extremely high-risk group (P=1.00). ROC curve results showed that the area under the curve (AUC) was 0.792 (P＜0.01).When the expression level of miR-181b was at the threshold value of 0.279, it showed a better sensitivity (62.9%) and specificity (91.8%). Survival analysis results suggested that compared with the high expression group, the miR-181b low expression group had poor PFS (log rank: P=0.047). Prediction of miR-181b by using the starBase, targetscan and picTar database and its combination with literature reports indicated that CARD11, ZFP36L1, RUNX1, NR4A3, ATP1B1, PUM1 and PLAG1 related with blood diseases, and up-regulated CARD11 and ZFP36L1 participated in lymphoid tumor formation by promoting cell proliferation and inhibiting cell aging. CONCLUSION The expression level of miR-181b in CLL group are significantly lower than that in the controls group, and the low expression of miR-181b relates with poor prognosis of CLL patients. Through bioinformatics prediction and combined with literature reports, it is speculated that CARD11 and ZFP36L1 as target genes of miR-181b may be participated in the occurrence and development of CLL. Further experiments are needed to verify this result.
Apoptosis Regulatory Proteins ; Cell Proliferation ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; MicroRNAs ; Prognosis

The study is aimed to investigate the effects of light intensities on growth,photosynthetic physiology,antioxidant systems and chemical composition of Viola yedoensis and provide cultivation references for V.yedoensis.Five groups of V.yedoensis were planted under five light intensities conditions,namely 100%,80%,50%,35%,5%of full sunlight,and then morphological index,growth,chlorophyll fluorescence parameters,photosynthetic parameters and antioxidant enzyme system indexes were measured during harvest.The results showed that there was no significant difference in the biomass of V.yedoensis among 35% -100%full sunlight,but the biomass of those were significantly higher than that in the 5%full sunlight treatment(P<0.05).The net photosynthetic rate,transpiration rate,stomatal conductance,intercellular CO_2 concentration and water use efficiency increased firstly and then decreased with the decrease of light intensity;F_m,F_v/F_mand Yield in 5% full sunlight treatment were significantly lower than those in the other four groups(P<0.05).The structure of chloroplast was normal under light intensity ranged from 50%to 100% full sunlight.The lamellar concentration of chloroplast matrix decreased and the starch granules decreased in 35% full sunlight treatment,and the margin of lamellar layer of chloroplast and substrate were blurred,and the starch granules were small and the number of starch granules decreased significantly under 5% full sunlight.MDA content in 5%full sunlight treatment was significantly higher than those in the other four groups(P<0.05).The total coumarin content and total flavonoid content decreased with the decrease of light intensity.In summary,the light in-tensity range suitable for the growth of V.yedoensis is wide(ranging from 35% to 100% full sunlight).The content of flavonoids and coumarins is positively correlated with light intensity.
Biomass ; Chlorophyll ; Chloroplasts ; Photosynthesis ; Plant Leaves ; Sunlight ; Viola

A total of ten compounds were isolated from the 90% Et OH extract of Cassia siamea by using various chormatographic techniques,and their structures were established as( 2' S)-2-( propan-2'-ol)-5,7-dihydroxy-benzopyran-4-one( 1),chrobisiamone( 2), 2-( 2'-hydroxypropyl)-5-methyl-7-hydroxychromone( 3), 2,5-dimethyl-7-hydroxychromone( 4), 2-methyl-5-acetonyl-7-hydroxychromone( 5),3-O-methylquercetin( 6),3,5,7,3',4'-pentahydroxyflavonone( 7),luteolin-5,3'-dimethylether( 8),4-( trans)-acetul-3,6,8-trihydroxy-3-methyl-dihydronapht halenone( 9) and 6-hydroxymellein( 10) based on the spectroscopic data.Compound 1 was a new compound,and 3,4,6,8 were isolated from this plant for the first time.
Cassia ; Luteolin ; Senna Plant ; Spectrum Analysis

BACKGROUND: Adipose-derived mesenchymal stem cells (ADMSCs) have been reported to improve wound healing. However, type I collagen secreted by ADMSCs will contribute to scar formation. Therefore, inhibiting type I collagen secretion from ADMSCs will strengthen its clinical application. OBJECTIVE: To investigate the effect of 1,25(OH)2D3on secretion of type I collagen by ADMSCs and its mechanism. METHODS: Human ADMSCs were isolated by collagenase digestion, and identified by flow cytometry. ADMSCs at passage 4 were cultured in DMEM/F12 medium containing different concentrations of 1,25(OH)2D3(10-7, 10-8, 10-9, 10-10and 0 mol/L) respectively for 4 days. Then, the concentration of type I collagen in cell supernatant was measured by ELISA. Real-time PCR and western blot were used to detect the expression of Smad3 at mRNA and protein levels and phosphorylated protein Smad3 level in ADMSCs cultured with and without 1,25(OH)2D3. To analyze the contribution of Smad3 to the effect of 1,25(OH)2D3, Smad3 inhibitor was added to culture medium 30 minutes before adding 1,25(OH)2D3, and type I collagen in cell supernatant was detected by ELISA at 4 days after addition of SMAD3 inhibitor. RESULTS AND CONCLUSION: 1,25(OH)2D3inhibited the secretion of type I collagen by ADMSCs in a dose-dependent manner. The results of real-time PCR and western blot showed that the expression of Smad3 was upregulated by 1,25(OH)2D3, and the results of western blot showed that the phosphorylated Smad3 protein level in ADMSCs was significantly increased by 1,25(OH)2D3. Moreover, the inhibition of type I collagen secretion by 1,25(OH)2D3could be blocked by Smad3 inhibitor. These results indicate that 1,25(OH)2D3can inhibit the secretion of type I collagen from ADMSCs by up-regulating the expression of Smad3.

OBJECTIVETo establish an modified rabbit model of the acute lung injury induced by cardiopulmonary bypass (CPB) with ascending aorta and right atrium catheterization and detect the changes in serum tumor necrosis factor-α (TNF-α) level after modeling.

METHODSTen healthy adult male New Zealand rabbits were randomly selected to establish CPB models. The model establishment was deemed successful if the rabbits survived for over 4 h with stable heart beat after termination of CPB. The vital signs of the rabbits were recorded after anesthesia (T), before CPB (T), at 15 after blocking the ascending aorta and pulmonary artery (T), immediately after re-opening of the ascending aorta and pulmonary artery (T), and at 1 (T) and 4 (T) after CPB. Arterial blood gas (ABG) was monitored at T, Tand Tand the serum levels of TNF-α were also detected with ELISA.

RESULTSNine rabbit models of CPB with acute lung injury were successfully established. During the operation, the MAP was maintained at a level above 55 mmHg, HCT significantly decreased from (30.18∓2.88)% at Tto (17.73∓1.95)% at T(P<0.05), and plasma lactate level increased significantly from 3.65∓1.13 mmol/L at Tto 9.36∓1.28 mmol/L at T(P<0.05). The oxygenation index (PaO/FiO) at Twas significantly lower than that at T(281.64∓55.76 vs 468.36∓56.28 mmHg, P<0.05). The serum levels of TNF-α were significantly increased (P<0.05) and obvious lung interstitial edema and inflammatory cell infiltration occurred after CPB establishment.

CONCLUSIONThe modified rabbit model of CPB with acute lung injury is stable and reliable and can be used for studying acute lung injury induced by CPB.