Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related death,following lung cancer,colorectal cancer and gastric cancer.Chemoresistance is currently the major challenge in clinical treatment of HCC patients,and it is also the primary cause of the poor prognosis and high recurrence rate of patients.There are multiple factors and complex mechanisms in the occurrence of HCC drug resistance.Recent research has shown that non-coding RNA(ncRNA)is closely related to HCC chemoresistance.By regulating the expression of target genes and protein translation,ncRNA affects the occurrence,metastasis,and prognosis of HCC and is expected to become a therapeutic biomarker and potential drug therapeutic target for HCC.Therefore,this study reviews several common ncRNAs,including long non-coding RNAs(LncRNAs),miRNAs and transferRNA(tRNAs),in the molecular mechanisms and research progress of HCC chemoresistance,providing new ideas for solving the problem of HCC chemoresistance.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective:To explore the relationship between rs671 (ALDH2), rs1229984 (ADH1B), RS141973904 (ADH1C), RS1799971 (OPRM1), rs1997794 (PDYN) polymorphism and individual's alcohol subjective response and drinking behavior.Methods:From January to December 2018, patients with alcohol dependence who were hospitalized in the First Affiliated Hospital of Xinjiang Medical University and Xinjiang mental health center and met the DSM-IV were selected (alcohol dependence group, n=100). Alcohol dependence patients and normal healthy subjects (control group, n=100) completed general demographic questionnaire, including drinking behavior such as the frequency of drinking each week and the maximum alcohol consumption at one drink, and informed consent, then were extracted of venous blood for DNA test.After that, alcoholics completed the alcohol challenge test.Biphasic alcohol effect scale(BAES) and drug effect questionnaire (DEQ) were completed before drinking and after drinking 30, 60, 120, 180 minutes respectively.Hardy-Weinberg equilibrium for genetic linkage analysis was calculated by utility program.Pearson Chi-square test was used to analyze the odds ratio(OR) value, and the chi-square test of repeated measured variables were used to analyze the variation trend of individual subjective response to alcohol after drinking. Results:rs671 allele A was associated with alcohol dependence risk (χ 2=23.97, P<0.01, OR=7.11, 95% CI=2.93~17.30), and for rs1229984 polymorphism the dominant genetic model " T/T-C/T" was taken as the best fitting model ( P<0.01, OR=0.16, 95% CI=0.08-0.32), which was a protective factor for alcohol dependence.Alcoholics with TT genotype in rs1229984 had lower maximum alcohol consumption ( F=4.86, P=0.01) and weekly alcohol consumption ( F=4.51, P=0.01) than those with CC and CT genotype.The maximum alcohol consumption ( F=20.28, P<0.01) and weekly alcohol consumption ( F=12.46, P<0.01) of individuals with GG and GA genotype in rs1799971 were higher than those with AA genotype.The AA genotype of rs1799971 showed lower stimulative effect ( F=7.99, P=0.01), higher sedative effect ( F=57.04, P<0.01), and lower " like" ( F=13.38, P<0.01) and " more" effect ( F=26.37, P<0.01) than that with GG and GA genotype. Conclusion:rs671 and rs1229984 are more closely related to individual drinking behavior and volume of alcohol consumption.rs1799971 is not only related to individual drinking behavior, but also has a more closed relationship with subjective response to alcohol.

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.

Objective:To evaluate the impact of short-term low-medium dose of corticosteroids on the clinical outcomes of patients with community-acquired pneumonia due to influenza A (FluA-CAP).Methods:This was a multicenter, retrospective study, including 693 patients hospitalized with FluA-CAP from Beijing Jishuitan Hospital, Qingdao Municipal Hospital, Beijing Huimin Hospital, Beijing Chao-Yang Hospital and the 2nd People′s Hospital of Yunnan Province during January 1, 2013 to December 31, 2018. The clinical characteristics of patients with or without corticosteroids administration were compared. The first dose of corticosteroids was administrated within 72 hours after admission, with the average dose of methylprednisolone (0.6±0.3) mg/(kg·d) and duration of (4.0±1.2) days. An adjusted logistic regression model was performed to assess the impact of corticosteroids treatment on the clinical outcomes (noninvasive ventilation, invasive ventilation, vasopressor use, admittance to intensive care unit (ICU), 30-day mortality, hyperglycemia needing insulin treatment and gastrointestinal bleeding). Mann-Whitney test and χ2 test were used for the statistical analysis. Results:Among the 693 patients, 132 patients received corticosteroids. Logistic regression analysis revealed that asthma (odd ratios ( OR)=15.528, 95% confidence interval ( CI) 1.953-123.484, P=0.01), chronic obstructive pulmonary disease ( OR=21.904, 95% CI 4.548-105.504, P<0.01) and arterial partial pressure of oxygen (PaO 2)/fraction of inspired oxygen (FiO 2)<300 mmHg (1 mmHg=0.133 kPa, OR=2.701, 95% CI 1.513-4.822, P<0.01) were independent risk factors for corticosteroids use in the FluA-CAP patients. An adjusted logistic regression model showed that low-medium dose corticosteroids administration was associated with decreased risks for early (defined as zero to three days after the first dose of corticosteroids) noninvasive ventilation ( OR=0.342, 95% CI 0.156-0.750, P<0.01), and increased risk for late (defined as four to 14 days after the first dose of corticosteroids) vasopressor use ( OR=2.651, 95% CI 1.913-6.306, P<0.01), late hyperglycemia which needed insulin treatment ( OR=9.739, 95% CI 2.174-21.769, P=0.019), ICU admission ( OR=3.075, 95% CI 1.166-8.143, P<0.01) and the 30-day mortality ( OR=2.372, 95% CI 1.337-4.549, P<0.01). In patients with asthma or chronic obstructive pulmonary disease ( OR=2.343, 95% CI 1.145-4.073, P<0.01) and PaO 2/FiO 2<300 mmHg ( OR=1.961, 95% CI 1.029-4.212, P<0.01), corticosteroids administration increased the risk of 30-day mortality. Conclusion:Low-medium corticosteroids treatment is associated with poor outcomes of FluA-CAP patients, and is not recommended to be used routinely.

Objective To assess the impact of short-term, low-dose systemic glucorticosteroids treatment on the clinical outcomes in patients with severe community-acquired pneumonia (SCAP). Methods A multi-center retrospective study was conducted. Data of patients hospitalized with SCAP in five teaching hospitals from Beijing, Shandong and Yunnan Provinces from January 1st, 2013 to December 31st, 2015 were reviewed. Patients were divided into steroids group and non-steroids group according to whether treated with glucorticosteroids during the disease course or not. Data of patients were reviewed, including gender, age, underlying disease, blood routine, biochemical examination and radiology findings (the worst value was recorded if there were more than one value), supportive treatment, complications (hyperglycemia needing insulin treatment and gastrointestinal bleeding) and clinical outcomes [early (0-3 days) treatment failure, late (4-14 days) treatment failure and 30-day mortality, treatment failure was defined as one of the followings: needing noninvasive or invasive ventilation, needing vasopressor use or death]. Univariate and multivariate Logistic regression was performed to evaluate the impact of short-term, low-dose systemic glucorticosteroids on the clinical outcomes in SCAP patients. Results Overall, 3 561 immunocompetent adult and adolescent patients with community-acquired pneumonia (CAP) were screened, 132 SCAP patients were entered into final analysis, including 24 patients in steroids group and 108 patients in non-steroids group. The patients in steroids group were prescribed with methylprednisolone (0.6±0.1) mg·kg-1·d-1 for (4.0±1.7) days. Compared with patients in non-steroids group, patients in steroids group showed younger age [years old: 70.5 (59.0, 75.0) vs. 80.0 (76.0, 85.0)], less frequency of male [41.7% (10/24) vs. 72.2% (78/108)], less comorbidities with cardiovascular [16.7% (4/24) vs. 42.6% (46/108)] and cerebrovascular disease [0% (0/24) vs. 40.7% (44/108)], less confusion [16.7% (4/24) vs. 40.7% (44/108)]; more frequency of chronic obstructive pulmonary disease [COPD, 41.7% (10/24) vs. 13.0% (14/108)], asthma [25.0% (6/24) vs. 1.9% (2/108)], chronic hepatic disease [8.3% (2/24) vs. 0% (0/108)] and respiratory rate≥30 times/min [33.3% (8/24) vs. 9.3% (10/108)] with significant differences (all P < 0.05), the proportion of guideline-based empirical antimicrobial therapy, early needing noninvasive ventilation, late gastrointestinal bleeding, early and late hyperglycemia needing insulin treatment were higher in steroids group than non-steroids group [50.0% (12/24) vs. 21.3% (23/108), 33.3% (8/24) vs. 7.4% (8/108), 20.8% (5/24) vs. 4.6% (5/108), 20.8% (5/24) vs. 1.9% (2/108), 37.5% (9/24) vs. 2.8% (3/108), all P < 0.05]. Adjusted by gender, age, comorbidities and empirical antimicrobial therapy, Logistic regression confirmed short-term, low-dose systemic glucorticosteroids was associated with higher risk for vasopressor usage [odds ratio (OR) = 3.369, 95% confidence interval (95%CI) = 1.369-6.133, P = 0.035], hyperglycaemia needing insulin treatment (OR = 4.738, 95%CI = 1.890-8.652, P = 0.017) in late stage and 30-day mortality (OR = 2.187, 95%CI = 1.265-4.743, P = 0.002). Conclusion Adjunctive treatment with short-term, low-dose systemic glucorticosteroids worsen the clinical outcomes and should not be used to SCAP patients routinely.

Objective:To investigate the prognostic significance of high sensitivity-C reactive protein (Hs-CRP) in patients with peripher-al T-cell lymphoma (PTCL). Methods:A total of 234 newly diagnosed PTCL patients with a median age of 48 years were analyzed retro-spectively. Serum Hs-CRP levels and other factors, including tumor stage and international prognostic index (IPI), were determined. Af-ter a median follow-up of 23 months, the relationship between Hs-CRP and overall survival (OS) was observed. Results:Serum Hs-CRP level positively correlated with IPI score (r=0.132, P<0.001), tumor stage (r=0.183, P=0.005), B symptoms (r=0.225, P=0.001), and lactic dehydrogenase (r=0.169, P=0.009), but negatively correlated with plasma albumin levels (r=?0.343, P<0.001), hemoglobin concentra-tion (r=?0.239, P<0.001), and platelet count (r=0.131, P=0.045), and is uncorrelated with age (P>0.05), gender (P>0.05), fitness score (P>0.05), and leukocyte count (P>0.05). Patients with serum Hs-CRP levels≤10 mg/L had better OS than patients with serum Hs-CRP levels>10 mg/L. Univariate and multivariate Cox regression models showed that platelet count, Hs-CRP, albumin levels, and IPI score were independent adverse prognostic factors. Conclusion:The baseline Hs-CRP level can serve as a major indicator of prognosis in PT-CL patients.

Objective To preliminarily investigate the levels of interleukin (IL)-1 family and IL-34 in serum of patients with ankylosing spondylitis (AS) and their roles.Methods Serum IL-1 family levels were detected from 6 AS patients and 4 healthy controls by using protein-chip technique.Enzyme-linked immunosorbent assay (ELISA) method was used to detect the levels of serum IL-34 from 65 AS patients and 85 healthy controls and the relationships of serum IL-34 levels and clinical or laboratory features were analyzed.T test and Spearman correlation were used for statistical analysis.Results IL-1Ra [(3302±1352) pg/ml vs (10778±2764) pg/ml]and IL-36Ra [(1363±194) pg/ml vs (3875±996) pg/ml] levels were significantly down-regulated in AS patients compared with that of healthy controls (t=5.363 and 4.289 respectively,both P＜0.05).The levels of IL-1α,IL-18,IL-36α and IL-37 were increased more remarkable in AS patients than in healthy controls (t=-2.532,-5.400,-5.023 and-5.783 respectively,both P＜0.05).Moreover,serum IL-34 levels were elevated more significantly in AS patients than in healthy controls [(169±153) pg/ml vs (54±31) pg/ml,t=6.722,P＜0.01] and were positively correlated with the levels of CRP and ESR.Serum IL-34 levels were markedly up-regulated in human leukocyte antigen (HLA)-B27 positive patients than in HLA-B27 negative patients(P＜0.05).Conclusion Part of IL-1 family and IL-34 may be involved in inflammatory or immunological process of AS.

OBJECTIVETo observe the short- term effects of hemogram in donors after peripheral blood stem cell（PBSC）collection and donors' tolerance.

METHODSA total of 166 related allogeneic donors were selected from The First Affiliated Hospital of Medical School of Zhejiang University between January 2013 and December 2014, including 86 male and 80 female. All donors accepted granulocytecolony- stimulating factor（G-CSF）5-10 μg·kg⁻¹·d⁻¹ until collection finished and were measured by blood cells count before and after PBSC collection.

RESULTSAfter PBSC collection, the hemoglobin level decreased from 145（94-181）g/L to 138（93-167）g/L, and the platelet counts decreased in all donors from 231（105- 490）× 10⁹/L to 95（39- 210）× 10⁹/L. The amount of hemoglobin contamination in collection products was weak correlated with the decreased hemoglobin in peripheral blood（r=0.297, P=0.017）, and the platelet contamination was high correlated with that decreased in peripheral blood（r=0.719, P<0.001）. The decline of hemoglobin level after twice PBSC collection was of no significant difference between four groups in different ages（P≥0.05）. The decline of platelet counts was out of a significant difference（P> 0.05）. In addition, the decline of hemoglobin level after once and twice PBSC collection was of a significant difference between four groups in different body mass index（BMI）（P=0.003 and P<0.001）, especially in thinner group with obvious decrease. But the decline of platelet counts was out of a significant difference （P>0.05）.

CONCLUSIONThe hemoglobin level decreased mildly in healthy allogeneic hematopoietic stem cell donors after PBSC collection and it is better to adjust parameters every time to ensure their safety for thinner donors. However, it will increase the risk of platelet decline, which is unrelated with ages and BMI and can be tolerated.

Blood Donors ; Blood Platelets ; Female ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Hematopoietic Stem Cells ; cytology ; Hemoglobins ; analysis ; Humans ; Male ; Platelet Count

OBJECTIVETo study the therapeutic effect of intranasal administration of temozolomide (TMZ) for brain-targeting delivery in a rat model bearing orthotopic C6 glioma xenografts.

METHODSForty Wistar rat bearing brain C6 glioma xenograft were randomly divided into 4 groups and treated with physiological saline solution or with TMZ by intravenous injection, gavage or intranasal administration. The tumor size, rat survival time and pathological changes were observed in each group.

RESULTSMagnetic resonance imaging showed a significantly reduced volume of glioma in intranasal TMZ group compared with that in the control, intraveneous TMZ injection group and TMZ gavage groups (12.45∓2.49 mm(3) vs 60.16∓4.12, 33.17∓3.56, and 35.16∓4.36 mm(3), respectively, P<0.05). The median survival time of the C6 glioma-bearing rats was also significantly longer in intranasal TMZ group than in the other 3 groups (31.0 days vs 20, 19, and 21.5 days, respectively, P<0.05). In the glioma xenografts, PCNA expression was the lowest and tumor cell apoptosis rate the highest in intranasal TMZ group.

CONCLUSIONIntranasal TMZ administration can suppress the growth of C6 glioma in rats and may serve as an effective strategy for glioma treatment.

Administration, Intranasal ; Animals ; Antineoplastic Agents, Alkylating ; administration & dosage ; Apoptosis ; Brain Neoplasms ; drug therapy ; Cell Line, Tumor ; Dacarbazine ; administration & dosage ; analogs & derivatives ; Drug Delivery Systems ; Glioma ; drug therapy ; Magnetic Resonance Imaging ; Neoplasm Transplantation ; Rats ; Rats, Wistar