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A single-center retrospective was performed with consecutive de novo BCR-ABL1-positive acute lymphoblastic leukemia (ALL) patients who received TKI-containing therapy between January 2010 and December 2018 to review the incidence, treatment, and outcome of the T315I mutation. A total of 38 (18%) patients harbored the T315I mutation in this period. According to the type of salvage therapy, patients were divided into subgroups of hematopoietic stem cell transplantation (HSCT) recipients (n = 9) and HSCT nonrecipients (n = 29). In the latter subgroup, there were 7 patients who newly acquired the T315I mutation after HSCT, and the median time was 10.8 months. In addition to these 7 cases, 5 out of 22 patients were managed with chimeric antigen receptor (CAR) T cells and ponatinib. There were 4 patients in the HSCT recipient subgroup who were treated with CAR-T cells or ponatinib before HSCT. The complete molecular remission (CMR) and recurrence rate of HSCT recipients were both 67%, and the median recurrence time was 3.6 months. A better overall survival (OS) was observed in the HSCT recipient subgroup than in the HSCT nonrecipient subgroup (median of 12.3 months vs 3.3 months, respectively; p = 0.004). Compared with patients who were not bridging to HSCT, the patients who were treated with CAR-T cells and/or ponatinib and bridged to HSCT tended to have a better OS (median of 3.3 months vs 13.3, respectively; p = 0.09). In conclusion, the outcomes in ALL patients with the T315I BCR-ABL1 mutation were poor. A better OS can be achieved through ponatinib, CAR-T cells, and bridging to HSCT, but it also has a higher risk of recurrence.
Subject(s)
Antineoplastic Agents/therapeutic use , Fusion Proteins, bcr-abl/genetics , Genes, abl , Imidazoles/therapeutic use , Molecular Targeted Therapy , Mutation, Missense , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Protein Kinase Inhibitors/therapeutic use , Pyridazines/therapeutic use , Adolescent , Adult , Amino Acid Substitution , Combined Modality Therapy , Dasatinib/therapeutic use , Disease-Free Survival , Female , Fusion Proteins, bcr-abl/antagonists & inhibitors , Hematopoietic Stem Cell Transplantation , Humans , Immunotherapy, Adoptive , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Prognosis , Recurrence , Remission Induction , Risk , Salvage Therapy , Young AdultABSTRACT
Berberine is an alkaloid extracted from medicinal plants such as Coptis chinensis and Phellodendron chinense. It possesses anti-inflammatory, anti-tumour and anti-oxidation properties, and regulates Glc and lipid metabolism. This study explored the mechanisms of the protective effects of berberine on barrier function and inflammatory damage in porcine intestinal epithelial cells (IPEC-J2) induced by LPS. We first evaluated the effects of berberine and LPS on cell viability. IPEC-J2 cells were treated with 5 µg/ml LPS for 1 h to establish an inflammatory model, and 75, 150 and 250 µg/ml berberine were used in further experiments. The expression of IL-1ß, IL-6 and TNF-α was measured by RT-PCR. The key proteins of the NF-κB/MAPK signalling pathway (IκBα, p-IκBα, p65, p-p65, c-Jun N-terminal kinase (JNK), p-JNK, p38, p-p38, ERK1/2 and p-ERK1/2) were detected by Western blot. Upon exposure to LPS, IL-1ß, IL-6 and TNF-α mRNA levels and p-IκBα p-p65 protein levels were significantly enhanced. Pre-treatment with berberine reduced the expression of inflammatory factors and was positively correlated with its concentration, and dose dependently inhibited the expression of IκBα, p-IκBα, p-p65, p-p38 and JNK. These results demonstrated that pre-treating intestinal epithelial cells with berberine was useful in preventing and treating diarrhoea induced by Escherichia coli in weaned pigs.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Berberine/pharmacology , Escherichia coli Infections/immunology , Escherichia coli/physiology , Intestinal Mucosa/metabolism , Swine/immunology , Animals , Cells, Cultured , Coptis , Cytokines/metabolism , Gene Expression Regulation , Inflammation Mediators/metabolism , Intestinal Mucosa/pathology , Lipopolysaccharides/immunology , Mitogen-Activated Protein Kinase Kinases/metabolism , NF-kappa B/metabolism , Phellodendron , Signal TransductionABSTRACT
BACKGROUND:Inhibitory control and drug craving are the core elements of evaluating drug withdrawal in methamphetamine addicts,which has attracted much attention in academic circles.As we all know,in order to achieve complete abstinence from drug addiction,the key is to restore the damaged inhibition and control function of drug addicts and effectively reduce the craving for drugs. OBJECTIVE:To systematically analyze the relationship between exercise and methamphetamine abstinence inhibitory control and drug craving,to find out an effective exercise intervention scheme that can promote methamphetamine abstinence,and to further explore the internal mechanism of exercise,in order to provide theoretical support and applied reference for the future use of exercise in drug withdrawal. METHODS:CNKI,WanFang,VIP,Web of Science,and PubMed databases were searched for relevant literature using the keywords of"exercise,physical activity,methamphetamine,inhibitory function,craving,addiction"in Chinese and"sport*,exercise,methamphetamine,drug craving,executive function,addiction"in English.According to the inclusion and exclusion criteria,86 documents were finally included for review. RESULTS AND CONCLUSION:In terms of inhibitory control in methamphetamine abstinent individuals,either acute and long-term moderate-intensity aerobic exercise or acute high-intensity interval training can significantly improve the inhibitory control capacity of methamphetamine abstinent individuals.For long-term aerobic exercise,aerobic group exercise or full-body comprehensive exercise is more effective.If the exercise format is power cycling,it is recommended to increase the frequency of exercise intervention.In terms of the drug craving intensity in methamphetamine abstinent individuals,acute moderate-intensity aerobic exercise and resistance training,as well as long-term moderate-intensity,high-intensity,or progressive load aerobic and resistance training,can effectively reduce the drug craving in methamphetamine abstinent individuals.Exercise exerts intrinsic regulatory effects on methamphetamine-mediated addiction.Exercise can influence the expression of tyrosine hydroxylase in the brain's ventral tegmental area,thereby stimulating the expression of dopamine receptor coupling proteins and promoting dopamine synthesis in the brain's reward regions,thereby compensating for dopamine depletion caused by methamphetamine addiction.Furthermore,exercise can also regulate protein kinase A inhibitors,affecting the protein kinase A signaling pathway mediated by dopamine D1 receptors,by inhibiting protein kinase A,thus affecting cAMP response element-binding protein and regulating methamphetamine addiction.Additionally,exercise can also,at the genetic level,affect the expression of the c-fos gene in the brain's nucleus accumbens region,activate a subset of glutamatergic neurons in this area,generate a rewarding effect,and thus improve methamphetamine addiction.Although current research has confirmed the relationship between exercise and methamphetamine addiction and has clarified the brain mechanisms underlying the effects of exercise,whether there are other brain regulatory pathways for the effects of exercise remains to be explored through more scientifically rigorous animal or human experiments,starting from the cellular or molecular level.
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Type 2 diabetes mellitus(T2DM)is a common chronic metabolic disease,while there is no consistent conclusion on the pathogenesis of T2DM.With the innovation of microecological research technology,intestinal dysbiosis is considered to be one of the causes of T2DM.Exercise is one of the effective means of diabetes management,while mechanism of regulating glucose metabo-lism still has many problems to be solved.In recent years,people have found that exercise can improve the intestinal environment and intestinal flora.This article will review the research on the influence and mechanism of exercise on T2DM based on intestinal flora,aiming to provide new ideas for exploring how exercise can improve T2DM in the future.
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Objective:To analyze the relationship between early-life famine exposure and the risk of metabolic syndrome in Chinese population.Methods:Relevant literature on the relationship between early-life famine exposure and the risk of metabolic syndrome in the Chinese population was retrieved from databases such as CNKI, Wanfang, VIP, CBM, Web of Science, and PubMed. The search was conducted from the inception of the databases up to October 2022. Two researchers independently extracted and systematically evaluated the data from the literature, and meta-analysis was performed using Stata 16.0 software. Results:A total of 12 publications met the inclusion criteria, including 71 470 study subjects. Meta-analysis results showed that early-life famine exposure increased the risk of metabolic syndrome in the Chinese population( OR=1.28, 95% CI 1.16-1.40). Subgroup analysis showed that both fetal famine exposure( OR=1.25, 95% CI 1.03-1.52) and childhood famine exposure( OR=1.29, 95% CI 1.15-1.45) increased the risk of developing metabolic syndrome compared to the non-exposed group, and this significant association was only found in the female population. Conclusion:Early-life exposure to famine may increase the risk of developing metabolic syndrome in adulthood in the Chinese population, particularly among females.
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Objective:To evaluate the clinical efficacy of Yangxue-Qingnao granule combined with ligustrazine injection in the treatment of wind-phlegm entering collaterals syndrome of cerebral infarction. Methods:A total of 96 patients with cerebral infarction and wind-phlegm entering collaterals syndrome to Suixi County Hospital of Traditional Chinese Medicine from January 2019 to December 2019 were selected and randomly divided into two groups by random number table method, with 48 in each group. The control group was given intravenous ligustrazine injection, and the observation group was given Yangxue-Qingnao granule on the basis of the treatment of the control group. Both groups were treated continuously for 2 weeks. TCM syndrome scores were performed before and after treatment, the National Institutes of Health Stroke Scale (NIHSS) was used to assess the degree of neurological impairment, and the Activity of Daily Living Scale (ADL) was evaluated. To evaluate the patient's quality of life, to detect the high-shear viscosity, low-shear viscosity and plasma viscosity of whole blood with an automatic hemorheology instrument. Results:The total effective rate of the observation group was 95.8% (46/48) and that of the control group was 70.8% (34/48). The difference between the two groups was statistically significant ( χ2=9.08, P<0.01). After treatment, the TCM syndrome score of the observation group was significantly lower than that of the control group ( t=3.51, P<0.01), the NIHSS score was significantly lower than that of the control group ( t=34.41, P<0.001), and the ADL score was significantly higher than that of the control group ( t=57.88, P<0.01). After treatment, the observation group's whole blood high shear viscosity [(5.04 ± 0.93)mPa?s vs. (5.64 ± 1.13)mPa?s, t=2.84], whole blood low shear viscosity [(11.32 ± 1.74)mPa?s vs. (13.39 ± 2.23)mPa?s, t=5.07] and plasma viscosity [(1.51 ± 0.33)mPa?s vs. (1.73 ± 0.47)mPa?s, t=2.65] of the observation group were significantly lower than those in the control group ( P<0.05 or P<0.01). Conclusion:Yangxue-Qingnao granule combined with ligustrazine injection can improve the neurological status and quality of life of patients with cerebral infarction syndrome of wind-phlegm entering the collaterals, and improve the clinical efficacy.
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Objective:To explore the significance of plasma homocysteine (Hcy) as a new biomarker for the differential diagnosis of postural tachycardia syndrome (POTS) and suspected myocarditis in children.Methods:A total of 24 children diagnosed with POTS and 21 children diagnosed with suspected myocarditis treated in the Pediatrics Department of the Peking University First Hospital from July to December 2016 were included in the study.Plasma Hcy levels were measured in each subject and compared between children with POTS and suspected myocarditis.The receiver operating characteristic (ROC) curves were depicted for assessing the diagnostic potential of Hcy in distinguishing POTS from suspected myocarditis.Results:Plasma Hcy level in the POTS group was significantly higher than that in the suspected myocarditis group [(14.25±8.09) μmol/L vs.(8.99±3.19) μmol/L], which was also significantly higher than that of the mean levels in Beijing children [(8.82±5.58) μmol/L] (all P<0.05). When the cut-off was 9.36 μmol/L, the area under the ROC curve was 0.76, and the sensitivity and specificity for distinguishing POTS from suspected myocarditis were 71% and 68%, respectively. Conclusions:Plasma Hcy levels are helpful in the differential diagnosis of POTS and suspected myocarditis in children.
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ObjectiveTo investigate the features of liver injury and related influencing factors in adolescents and adults with infectious mononucleosis (IM). MethodsA retrospective analysis was performed to investigate the features of liver injury in adolescents and adults with IM who were hospitalized in Peking University First Hospital from January 2005 to December 31 2018, and the patients were divided into subgroups based on age, Epstein-Barr virus (EBV) DNA level, and presence or absence of jaundice or infection with cytomegalovirus or hepatitis E virus (HEV). The t-test was used for comparison of continuous data meeting analytical conditions between two groups, and the Mann-Whitney U test was used for comparison of continuous data which did not meet analytical conditions between two groups; the chi-square test was used for comparison of categorical data between two groups, and the Fisher’s exact test was used for comparison of categorical data which did not meet the analytical conditions of the chi-square test. A logistic regression analysis was used for multivariate analysis. ResultsA total of 274 patients were enrolled, with 154 male patients (56.2%) and 120 female patients (43.8%), and the mean age of onset was 22.3±67 years. The incidence rate of liver injury [defined as alanine aminotransferase (ALT) >50 U/L and/or aspartate aminotransferase (AST)>40 U/L] was 97.4% (267/274), and that of jaundice was 27.6% (74/268). The patients, aged ≥20 years, tended to have a higher level of gamma-glutamyl transpeptidase (GGT) (Z=2.070, P=0.038). Serum EBV DNA was measured for 167 patients, among whom 90 had positive results and 77 had negative results. The positive serum EBV DNA group had significantly higher levels of GGT (Z=3.005, P=0.003) and lactate dehydrogenase (Z=2.162, P=0.031) than the negative serum EBV DNA group. The patients with cytomegalovirus infection tended to have a higher level of alkaline phosphatase (Z=2.351, P=0.019), and the patients with HEV infection presented with a higher level of GGT (Z=1.988, P=0.047). AST (odds ratio [OR]=1.006, 95% confidence interval [CI]: 1.002-1.010, P=0.005) and ALP (OR=1.012, 95%CI: 1.005-1.020, P=0.001) were independent risk factors for jaundice. ConclusionThere is a high incidence rate of liver injury in adolescents and adults with IM, and the patients with an older age or positive serum EBV DNA tend to have more severe liver injury.
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Objective:To compare the effects of phenoxybenzamine and doxazosin on intraoperative hemodynamics in patients with normotensive pheochromocytoma.Methods:Perioperative data of patients who underwent surgery for normotensive pheochromocytoma in Peking University First Hospital from January 1, 2004 to December 31, 2017 were collected.Patients were divided into phenoxybenzamine group and doxazosin group according to the type of preoperative α-blockade.The primary endpoint was intraoperative hemodynamic fluctuations.Secondary endpoints included postoperative circulatory support, complications, mortality, and etc.Results:Sixty-one patients were included in the study, with 24 cases in phenoxybenzamine group and 37 cases in doxazosin group.There was no significant difference in the area under the curve of intraoperative blood pressure fluctuation between the two groups ( P>0.05). The area under the curve of intraoperative heart rate >110 bpm was significantly greater in phenoxybenzamine group than in doxazosin group ( P<0.05). There was no significant difference in the secondary endpoints between the two groups ( P>0.05). Conclusion:The effect of preoperative administration of doxazosin or phenoxybenzamine on blood pressure fluctuation has no significantly statistical difference in patients with normotensive pheochromocytoma, and the patients took phenoxybenzamine preoperatively have an increased risk of intraoperative tachycardia.
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Objective:To understand the 10-year risk of ischemic cardiovascular disease (ICVD) in hypertensive patients in communities in Shenzhen, and to provide baseline data for the comprehensive implementation of community-based hypertension health management measures based on ICVD risk assessment.Methods:From July 2017 to June 2018, 200 community health service centers in 10 districts of Shenzhen were selected by multi-stage random sampling to investigate hypertensive patients in communities aged≥35. After the patients who met the inclusion criteria signed the informed consent form, the demographic characteristics, physical examination, and laboratory tests were conducted. The absolute risk of ICVD in 10 years was evaluated by using the ICVD risk assessment module from the Shenzhen community health service information system. According to the China 10-year risk for ICVD score tables, recommended by the Chinese cardiovascular disease prevention guidelines, the risk grade of ICVD was estimated and analyzed. In addition, the relative risk was used to eliminate the influence of gender and age, and the single sample t-test was used for comparisons with the larger population. Results:30 015 hypertensive patients from communities were investigated, including 16 165 (53.86%) males and 13 850 (46.14%) females, aged 35-102 years, with a median age of 59.0. 6 405 (21.34%), 5 771 (19.23%) and 17 839 (59.43%) were at high, medium and low risk of ICVD, respectively. The absolute risk was 3.77%, 95% CI (3.72%-3.82%). The risk grades of ICVD in 10 years was different as per gender, age, marital status, population type, smoking, family history of hypertension, history of diabetes mellitus, systolic blood pressure, body mass index, and total cholesterol level, P values were all<0.001. The risk grades of ICVD in males, married patients, floating populations, having a total cholesterol <5.20 mmol/L, non-smokers, non-diabetics, and having a family history of hypertension were lower than that of other characteristics, and increased with age, systolic blood pressure, and body mass index. Further analysis of 15 652 patients aged 35-59 years old showed that the 10-year risk of ICVD in patients with hypertension in communities was slightly higher than that of the larger population, and the relative risk was 1.27, 95% CI (1.25-1.28), t=37.648, P<0.001. In males, relative risk was 0.94, 95% CI (0.93-0.95), t= 9.906, P<0.001, and there were no significant trend changes among age groups. In females, relative risk was 2.05, 95% CI (2.01-2.09), t=72.207, P<0.001, and increased with age. Conclusion:The 10-year risk of ICVD in hypertensive patients is often at a high level in Shenzhen, so it is necessary to carry out the risk assessment of ICVD in the community. The effect of community hypertension health management on reducing the risk of ICVD may vary between genders. The risk of ICVD in male patients is lower than that of males in the larger population, but in female patients it is still much higher.
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Objective@#Meta-analysis was conducted on the tetanus antibody protection rate of healthy population born after 1978 in China (data from Hong Kong, Macao and Taiwan was excluded, the same below).@*Methods@#Search the data on China′s tetanus antibody level which were published in China National Knowledge Infrastructure, Wanfang data, VIP, SinoMed database, PubMed and the Cochrane Library. The Chinese search keywords were "Tetanus Antitoxin", "Tetanus Antibody", "Healthy Population" and "Mainland China". English search terms include "tetanus antitoxin", "tetanus vaccine", "tetanus vaccine", "general population" and "mainland of China". The time limit for inclusion in literature research was 2010-2019. Stata software was used to conduct meta-analysis on the protection rate of tetanus antibody.@*Results@#A total of 24 articles were included. There was no obvious publication bias in the included articles. The total number of respondents was 23 530, the antibody protection rate was 49.5%-99.0%. A total of 20 817 people got effective antibody protection, which meant the antibody level reached and exceeded 0.1 IU/ml, and the combined protection rate was 78.6% (95%CI: 75.0%-88.2%). The combined protection rates of antibody in 0-7 years old and 8-15 years old groups were 88.9% (95%CI: 86.9%-91.0%) and 79.3% (95%CI: 72.9%-86.2%) respectively. The combined protection rates of antibodies in 16-20 years old, 21-30 years old and 31-40 years old groups were 58.9% (95%CI: 46.5%-71.2%), 47.7% (95%CI: 16.8%-78.7%) and 63.8% (95%CI:32.6%-95.1%) respectively. The combined protection rate of tetanus antibody for 0-15 years old people was 85.6% (95%CI: 83.1%-88.1%), and the combined protection rate of antibody for 16-40 years old people was 52.9% (95%CI: 39.3%-66.6%).@*Conclusion@#With the increase of age, the protection rate of tetanus antibody among the healthy population aged 16-40 years in our country decreases. An individualized vaccination plan should be formulated according to the previous tetanus vaccination history and the tetanus antibody level when necessary.
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Objective@#To analyze the prognostic value of CD7 expression in newly diagnosed acute myeloid leukemia (AML) patients, and to further explore the correlation between CD7 expression and CEBPA mutation, and to clarify the prognostic value of CD7+ in AML patients with wild-type (WT) or mutant-type (MT) CEBPA.@*Methods@#The clinical data of 298 newly diagnosed non-M3 AML patients between January 2010 and December 2016 were analyzed retrospectively. The clinical characteristics and prognosis of CD7+ and CD7- patients were respectively compared in all patients, and in patients with WT and MT CEBPA. The relationship between CD7 expression and CEBPA mutation was determined by chi-square, and the effects of CEBPA mutation on survival and prognosis in CD7+ group by Kaplan-Meier method.@*Results@#In CD7+ group, the frequencies of CEBPA mutation were 10.1% (single site) and 33.9% (double site) , significantly higher than those of the CD7- group (5.3% and 4.2%) (P=0.000) . Subgroup prognostic analysis showed a lower CR rate (P=0.001) and a higher RR (P=0.023) in CD7+ group comparing to those of CD7- group in AML patients with wild type CEBPA. There were no statistical difference between CD7+ group and CD7- group in overall survival (OS) and disease free survival (P>0.05) , while in the CEBPA mutant group the CD7+ group has higher OS (P=0.019) and DFS (P=0.010) . Based on the CD7 expression and CEBPA mutation, 298 cases were divided into 3 subgroups, named as CD7+-CEBPA MT group, CD7- and CD7+-CEBPA WT group. The 3-year OS of the 3 groups were 80.2%, 48.0% and 30.6%, respectively (P<0.001) , and the 3-year DFS were 74.1%, 37.4% and 22.2%, respectively (P<0.001) .@*Conclusion@#The CEBPA mutation rate was higher in CD7+ AML patients then that of CD7- patients. CD7 expression has opposite prognostic significance in AML patients carrying the wild-type or mutant-type CEBPA. Based on CD7 expression and CEBPA mutation, a new risk stratification model can be established, which is helpful to guide the clinical individualized treatment for AML patients.
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Objective To explore the mediating effect of health-promoting lifestyle on the relationship between health literacy and stigma among middle-aged and elderly patients with type 2 diabetes mellitus (T2DM). Methods A stratified random sampling method was used to select 415 patients with T2DM from three general hospitals in Weifang to conduct a questionnaire survey using the Disease Stigma Assessment Scale for Type 2 Diabetes Mellitus (DSAS-2), the Health Literacy Scale, and the Type 2 Diabetes Health Promotion Scale (T2DHPS). Results Sickness stigma was negatively correlated with health literacy (r=-0.547, P<0.01) and negatively correlated with health promotion (r=-0.505, P<0.01), while health promotion was positively correlated with health literacy (r=0.398, P<0.01). Health-promoting lifestyle mediated the association between health literacy and stigma (β=0.0383, P<0.01), with the mediating effect accounting for 16.00% of the total effect. Conclusion Health literacy can influence the stigma of patients with type 2 diabetes mellitus through health promotion lifestyle, suggesting that the stigma of patients with diabetes can be improved through health promotion lifestyle intervention.
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Objective@#To explore the potential mechanism of pimecrolimus in airway remodeling of atopic dermatitis (AD) and asthma mice.@*Methods@#Female BALB/c mice were randomly divided into three groups: control group, atopic dermatitis group and pimecrolimus treatment group. The cell in bronchoalveolar lavage fluid (BALF) was calculated by Ray-Jimsa staining. The structural changes in lung tissue and skin tissue were observed by hematoxylin-eosin (HE) staining, and the level of interleukin (IL)-33, IL-5, IL-13 in serum was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of type 1 collagen (Col1) in the airway of mice were detected by RT-PCR and Western blotting. And western blotting was also used to determine the activation of mitogen-activated protein kinase P38 (P38MAPK) and mitogen-and stress-activated protein kinase 1 (MSK1) in the lungs of mice.@*Results@#Compared with those in the control group, the total number of leukocytes in bronchoalveolar lavage fluid (BALF) and the expression levels of IL-33, IL-13 and IL-5 in serum of atopic dermatitis group were significantly higher, and the difference was statistically significant (P < 0.05). In the atopic dermatitis group, the phosphorylation of P38MAPK and MSK1 protein was increased (1.50 ± 0.43 vs. 0.80 ± 0.43, 1.39 ± 0.08 vs. 0.62 ± 0.08) and the expression of Col1 protein and protein (1 vs. 3.20 ± 0.59, 1.40 ± 0.12 vs. 0.13 ± 0.16) was increased, and the difference was statistically significant (P < 0.05). After pimecrolimus treatment, the number of leukocytes in BALF, the levels of IL-33, IL-5 and IL-13 in serum (213.13 ± 11.89, 657.97 ± 86.47, 143.82 ± 33.02), the phosphorylation of P38MAPK and MSK1 protein in lung tissue (0.10 ± 0.04, 0.85 ± 0.05), and the expression of Col1 mRNA and Col1 protein were decreased (0.61 ± 0.22, 0.48 ± 0.08), and the difference was statistically significant (P < 0.05). The edema of lung and skin tissue and the infiltration of inflammatory cells were alleviated.@*Conclusions@#Pimecrolimus can alleviate the inflammation and airway remodeling in mice by inhibiting the activation of IL-33 related pathways, thereby reducing the incidence of asthma.
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OBJECTIVE: To prepare Ursolic acid (UA)/Pluronic F127 (PF127)/TPGS-doxorubicin (DOX) mixed nanomicelles, and to characterize it and study its in vitro release behavior. METHODS: UA/PF127/TPGS nanomicelles were prepared by thin film hydration method. Using encapsulation efficiency of UA as index, combined with the results of single factor tests, L9(34) orthogonal test was used to optimize drug dosage of UA, molar ratio of PF127 to TPGS, hydration temperature and hydration volume, validation test was performed. On the basis of succinylated TPGS, TPGS-DOX was synthesized and mixed with UA/PF127/TPGS to prepare UA/PF127/TPGS-DOX mixed nanomicelles, the appearance, particle size and critical micelle concentration (PF127/TPGS) were investigated. The drug release behavior was examined by dialysis bag diffusion method. RESULTS: The optimal preparation technology of UA/PF127/TPGS nanomicelles was as follows as drug dosage of UA 8 mg, molar ratio of PF127 to TPGS 3 ∶ 7, hydration temperature 50 ℃, hydration volume 4 mL. Average encapsulation efficiency of UA in nanomicelles was 89.00% (RSD=0.43%, n=3). The prepared UA/PF127/TPGS-DOX mixed nanomicelles solution was clear with opalescence. The nanomicelles were spherical and uniform in size; average particle size was (115.00±9.42) nm; critical micelle concentration of PF127/TPGS (molecular ratio 3 ∶ 7) was 0.001 3%. The in vitro drug release of UA and DOX in the mixed nanomicelles was significantly slowed down, compared with raw materials or substance control. The drug release process of the two drugs in the nanomicelles conformed to Weibull equation. CONCLUSIONS: UA/PF127/TPGS-DOX mixed nanomicelles are successfully prepared with uniform particle size, good stability and good sustained-release effect.
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OBJECTIVE We used Al lergic Rhinitis Control Test (ARCT) questionnaire to evaluate the control level of allergic rhinitis, in order to get the data of prevalence rate, epidemiological characters and risk factors of uncontrolled allergic rhinitis. METHODS Patients with AR were recruited from our department and the treatment based on the Allergic Rhinitis and Its Impact on Asthma(ARIA) guidelines. Telephone interview will be taken after 2 weeks in these patients, compared to symptoms, impact on quality of life, ARCT value before and after treatment. RESULTS Among 134 patients enrolled, moderate/severe AR account for 95%. After 2 weeks of treatment, both symptom and quality of life were marked improvement(P <0.001). Patients with uncontrolled AR(26.1%) at day 15 more frequently presented higher height and weight(P <0.001), history of ear, nose, and throat(ENT) infection or antibiotics intake for respiratory infection in the last 12 months (40.4% versus 62.9%, P =0.022), smoking (4.0% versus 17.1%, P =0.02), and smell disturbance (10.1% versus 25.7%, P =0.044). CONCLUSION Most of AR patients have remarkable improvements in symptom and quality of life after treatment, but 26.1% of patients still remain uncontrolled. Smoking and nose infection are risk factors of uncontrolled AR.
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PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. MATERIALS AND METHODS: Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP-14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. RESULTS: Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. CONCLUSION: R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.
Subject(s)
Humans , Asian People , B-Lymphocytes , Cyclophosphamide , Disease-Free Survival , Doxorubicin , Follow-Up Studies , Lymphoma, B-Cell , Prednisone , Prognosis , Rituximab , VincristineABSTRACT
Objective To investigate whether preset epidural catheter and individualized onset time could improve the effect of epidural labor analgesia.Methods This was an open-label,random-ized,controlled trial.The nulliparae aged from 18 to 35 years,with single cephalic term pregnancy, were randomized into two groups.In the individualized group,epidural catheterization was performed at the beginning of labor (emergence of regular contractions and nearly disappearance of cervix),and epidural analgesia was initiated when asked by parturients and the numeric rating scale (NRS,a verbal rating score from 0 to 10 for pain,in which 0 represented no pain and 10 the worst pain imagi-nable)pain score ≥ 5 .In the control group,epidural analgesia was initiated at cervical dilation of≥ 1 cm.The primary outcome measures were the most severe NRS pain score during labor and the pro-portion of the most severe NRS pain score ≥ 7 evaluated at 24 hours after delivery.Results A total of 194 parturients completed the study,among whom 97 were in the individualized group and 97 in the control group.The most severe labor pain score during labor [median 9 (IQR 8-10)in the individ-ualized group vs 9 (8-10)in the control group,P=0.201]and the proportion having the most severe pain score ≥ 7 [94 cases (96.9%)in the individualized group vs 89 cases (91.8%)in the control group,P=0.1 2 1 ]did not differ significantly between the two groups.There were no significant differences of adverse events between the two groups.Conclusion For the nulliparae with single ce-phalic term pregnancy suitable for vaginal delivery, the effects of individualized epidural labor analgesia are comparable to that of traditional analgesia (beginning at cervical dilation of ≥ 1 cm). The individualized analgesia is safe.
ABSTRACT
Objective To investigate the value of strong ion gap (SIG),anion gap (AG),and the anionic gap corrected by albumin (ACAG) and lactate in evaluating the prognosis of severe pneumonia in children. Methods Pediatric patients with severe pneumonia hospitalized in the Affiliated Hospital of North Sichuan Medical College from June 2014 to June 2017 were selected as study subjects. A total of 20 death pa-tients (death group) and 59 survivors (survival group) were analyzed respectively according to their progno-sis. The data of Na + ,K + ,Cl - ,HCO -3 ,Mg2 + ,Ca2 + ,pH,PaCO2 ,P,albumin and lactate were obtained from blood gas analysis and blood biochemistry. Based on these data,ACAG was calculated by the Henderson-hasselbalach formula and SIG was calculated by the Stewart-Figge formula. Results There were significant differences in ACAG,SIG,and lactate levels between death group and survival group(P < 0. 05). The area under the ROC curve of ACAG was 0. 756,and the area under the ROC curve of SIG was 0. 936,which were larger than the area under the diagnostic reference line (P < 0. 05),the results were statistically significant. The sensitivity and specificity of ACAG was 79. 7% and 70. 0% respectively,and the cut off was 12. 7. The sensitivity and specificity of SIG was 81. 4% and 95. 5% respectively,and the cut off was 2. 7. Conclusion SIG,ACAG and lactate have the guiding value in assessing the prognosis of children with severe pneumonia. Meanwhile,SIG has a greater guiding significance for the assessment of the prognosis of children with severe pneumonia.
ABSTRACT
Poor adherence to medication leads to symptom exacerbation and interferes with the recovery process for patients with schizophrenia. Following baseline assessment, 142 patients in medication maintenance at a community mental health center were randomized to one of 3 treatments for 9 months: (1) PharmCAT, supports including pill containers, signs, alarms, checklists and the organization of belongings established in weekly home visits from a PharmCAT therapist; (2) Med-eMonitor (MM), an electronic medication monitor that prompts use of medication, cues the taking of medication, warns patients when they are taking the wrong medication or taking it at the wrong time, record complaints, and, through modem hookup, alerts treatment staff of failures to take medication as prescribed; (3) Treatment as Usual (TAU). All patients received the Med-eMonitor device to record medication adherence. The device was programmed for intervention only in the MM group. Data on symptoms, global functioning, and contact with emergency services and police were obtained every 3 months. Repeated measures analyses of variance for mixed models indicated that adherence to medication was significantly better in both active conditions than in TAU (both p<0.0001). Adherence in active treatments ranged from 90-92% compared to 73% in TAU based on electronic monitoring. In-person and electronic interventions significantly improved adherence to medication, but that did not translate to improved clinical outcomes. Implications for treatment and health care costs are discussed.