Association between metabolism-related chronic disease combination and prevalence of non-alcoholic fatty liver disease in community residents in Shanghai / 中华流行病学杂志

Objective: To explore the combination of metabolism-related chronic diseases associated with the prevalence of non-alcoholic fatty liver disease (NAFLD) in community residents in Shanghai. Methods: The baseline data of Shanghai Suburban Adult Cohort and Biobank were used to understand the prevalence of five metabolism-related chronic diseases, including obesity, hypertension, hyperlipidemia, gout and diabetes, based on questionnaire survey, physical examination and blood biochemical detection. NAFLD was diagnosed by B-ultrasound detection and questionnaire. Multivariable logistic regression model was used to analyze the association of 31 metabolism-related chronic diseases combinations with the prevalence of NAFLD. Results: The median age (Q1, Q3) of 65 477 subjects was 60 (51, 66) years, and men accounted for 40.6%. The overall prevalence of NAFLD was 38.2%, and the prevalence of HAFLD in patients without any of the five metabolism-related chronic diseases was 12.0%. The chronic disease combination with the strongest association with NAFLD was obesity + hypertension + hyperlipidemia + gout + diabetes in the total population (OR=37.94, 95%CI: 31.02-46.41), in women (OR=36.99, 95%CI: 28.78-47.54) and in age group ≥60 years (OR=36.19, 95%CI: 28.25-46.36). The chronic disease combination with the strongest association with NAFLD was obesity + hyperlipidemia + gout + diabetes in men (OR=50.70, 95%CI: 24.62-104.40) and in age group <60 years (OR=49.58, 95%CI: 24.22-101.47). Conclusions: The prevalence of NAFLD in community residents in Shanghai was high. Attention needs to be paid to health of obese people and weight loss should be promoted for them. Community health education should be strengthened for patients complicated with gout, diabetes, hyperlipidemia and hypertension and it is necessary to correct abnormal serum uric acid, blood sugar, blood lipids and blood pressure in a timely manner to reduce the risk of NAFLD.

Prevalence and Factors Associated with Concomitant Chinese Medicine Use by Rheumatoid Arthritis Patients in A Multi-Ethnic Asian Population / 中国结合医学杂志

OBJECTIVE@#To determine the prevalence, factors associated with and patterns of concomitant Chinese medicine (CM) with Western treatment use among patients with rheumatoid arthritis (RA) in a tertiary referral centre (Singapore General Hospital) in Singapore.@*METHODS@#We conducted a cross-sectional interviewer-administered survey of a consecutive sample of patients with RA in Singapore General Hospital centre regarding their CM use including data on patient demographics, disease characteristics, concomitant use of CM and reasons, concerns and disclosure patterns from March to August 2015. Univariate and multivariate logistic regression analyses were performed to determine the associations of CM use.@*RESULTS@#Prevalence of CM use among the 258 patients surveyed (male: female 42: 216; Chinese: Malay: Indian 191: 29: 34; mean age: 61 years; mean duration of RA: 10 years) was 46.1% (119/258). On multivariate analysis, Chinese ethnicity (OR, 95% CI: 4.11, 1.49-11.36), Chinese speakers (OR, 95% CI: 2.35, 1.03-5.54), middle-income group (OR, 95% CI: 2.53, 1.01-6.31) and greater learned helplessness (OR, 95% CI: 1.13, 1.04-1.22) were significantly associated with CM use. More CM users disclosed their CM use to CM physicians (87.3%, 96/110), sought advice from them on treatment interactions (59.4%, 57/96) and how best to combine treatments (49.0%, 47/96) than did so with rheumatologists (42.0%, 50/119; 40.0%, 20/50; and 42.0%, 21/50, respectively). Forty-two percentage (29/69) of patients who concealed CM use from rheumatologists because their rheumatologists did not specifically enquire about CM use.@*CONCLUSIONS@#Concomitant CM use among patients with RA treated in a tertiary referral centre in Singapore is high but voluntary disclosure is low. The associations identified can help doctors identify and enquire about CM use, minimizing potential adverse interactions.

Protective effect of amifostine in the chemotherapy of malignant solid tumor in children / 肿瘤研究与临床

Objective:To explore the cellular protective effect and adverse reactions of amifostine in the chemotherapy of malignant solid tumor in children.Methods:A total of 62 children with malignant solid tumors receiving 253 times of chemotherapy who were admitted to the Pediatrics Single Center of Beijing Tongren Hospital from April 2018 to April 2020 were selected and divided into the experimental group (amifostine was used before chemotherapy, 113 times in total) and the control group (amifostine was not used before chemotherapy, 140 times in total) according to stratified random sampling. The self-control method was used to compare the therapeutic effects and adverse effects of the use of amifostine or not in the same child under the same chemotherapy regimen.Results:Compared with the control group, the duration of agranulocytosis [(6.7±3.0) d vs. (9.5±4.3) d, t = 3.788, P < 0.05], the duration of platelet reduction (<20×10 9/L) [(3.6±1.3) d vs. (5.4±3.2) d, t = 2.037, P < 0.05], the time of receiving recombinant human granulocyte colony-stimulating factor (rhG-CSF) treatment [(6.5±3.5) d vs. (10.0±2.8) d, t = 3.049, P < 0.05] and the time of antibiotic treatment during infection [(5.0±2.5) d vs. (8.2±2.5) d, t = 3.558, P < 0.05] in the experimental group were all shorter; the amount of platelet input required [(0.7±0.5) U vs. (1.5±0.8) U, t = 2.873, P < 0.05] was less than that of the control group. Oral mucosal ulceration occurred in only 4 (3.5%) times in the experimental group, which was lower than that in the control group [12 (8.6%) times] ( χ2 = 4.634, P = 0.033). Regardless of the cost of amifostine itself, there was a statistically significant difference in treatment cost between the experimental group and the control group ( P = 0.034), and the length of hospital stay in experimental group was relatively short ( P = 0.012). The patients were more prone to nausea and vomiting and hypocalcemia when treated with amifostine. Conclusions:Amifostine can effectively protect normal tissue cells in chemotherapy of children with malignant solid tumor and its adverse reactions are mild.

Diagnosis, treatment and prognosis of 10 children with advanced clear cell sarcoma of kidney / 中华实用儿科临床杂志

Objective:To investigate the clinical features, diagnosis, treatment and prognosis of advanced clear cell sarcoma of kidney(CCSK) in children.Methods:The clinical data of 10 children with advanced CCSK hospitalized in Department of Pediatrics of Beijing Tongren Hospital, Capital Medical University from January 2014 to December 2017 were collected, and their clinical features, diagnosis, treatment and prognosis were analyzed retrospectively.Results:(1) Clinical features of CCSK: ten cases of CCSK included 6 boys and 4 girls, with the median onset age of 32 months; 7 cases were left CCSK and 3 cases were right CCSK.There were 9 cases of stage Ⅲ and 1 case of stage Ⅳ at the time of initial diagnosis, when 4 cases were misdiagnosed as other renal tumors at the time of initial diagnosis(40%, 4/10 cases). Five patients with stage Ⅲ CCSK had recurrence and metastasis during treatment and follow-up, and the main distant metastasis sites were lung, bone, liver and brain.(2) Treatment and prognosis of CCSK: seven cases received surgery combined with radiotherapy and chemotherapy, and 3 cases whose parents gave up treatment adopted non-standardized treatment.The median follow-up time was 33.5 months.Seven patients survived and 3 cases died.The 3-year overall survival rate of all 10 patients was 65.6%.The 3-year overall survival rate of stage Ⅲ was 74.1%, and that of stage Ⅳ was 0.The prognosis of stage Ⅲ was significantly better than that of stage Ⅳ( χ2=9, P=0.003). Among the 5 recurrent cases, only 1 case achieved completely remission, 2 cases achieved partially remission, 1 case suffered from disease progression and 1 case died.The 3 cases without recurrence were given standardized treatment of surgery, che-motherapy and radiotherapy, and all were completely remitted. Conclusions:CCSK is easy to be misdiagnosed, and the risk of recurrence and distant metastasis is high in stage Ⅲ patients during treatment and follow-up.Stage Ⅲ patients who actively receive standard treatment including surgery, chemotherapy and radiotherapy have good prognosis, while the mortality of patients with relapse and distant metastasis is high.

Hypoxia and inflammation are risk factors for acute myocardial injury in patients with coronavirus disease 2019 / 北京大学学报(医学版)

OBJECTIVE@#To investigate the risk factors for acute myocardial injury in coronavirus disease 2019 (COVID-19) patients.@*METHODS@#This is a retrospective analysis of a COVID-19 cohort, in which 149 confirmed COVID-19 patients enrolled were divided into the group of myocardial injury (19 cases) and the group of non-myocardial injury (130 cases). Myocardial injury was defined according to Fourth universal definition of myocardial infarction released by European Society of Cardiology (ESC) in 2018, that cardiac troponin (cTn) was above 99th percentile of the reference level. Clinical information and results of laboratory tests of the eligible patients were collected. Factors associated with myocardial injury in COVID-19 patients were evaluated.@*RESULTS@#Compared with the group of non-injury, the patients in the group of injury were older and had a larger proportion of severe or critical cases (P < 0.05), higher respiratory rate and lower percutaneous oxygen saturation (SpO2) without oxygen therapy on admission (P < 0.05). All inflammatory indexes except for tumor necrosis factor α (TNF-α) showed significant elevation in the patients of the group of injury (P < 0.05). Analyzed by Spearman correlation test, we showed that the levels of circulatory cTnI were in positive correlation with the levels of high-sensitivity C-reactive protein (hs-CRP), ferritin, receptor of interleukin-2 (IL-2R), interleukin-6 (IL-6) and interleukin-8 (IL-8) (ρ > 0, P < 0.05). Lower SpO2 without oxygen therapy on admission (OR: 0.860, 95%CI: 0.779-0.949, P=0.003) and higher plasma IL-6 levels (OR: 1.068, 95%CI: 1.019-1.120, P=0.006) were independent risk factors for acute myocardial injury in the patients with COVID-19 by multivariate Logistic regression analyses.@*CONCLUSION@#Hypoxic state and inflammation may play a key role in the pathogenesis of acute myocardial injury in COVID-19 patients.

Survival of head and neck rhabdomyosarcoma in children: a clinical analysis of 98 cases / 中华全科医师杂志

Objective To analysis the prognosis of head and neck rhabdomyosarcoma (RMS) in pediatrics. Methods The clinical data of 98 pediatric patients with head and neck RMS admitted from February 2005 to September 2017 were retrospectively analyzed. The clinical staging and risk grouping were performed according to international rhabdomyosarcoma study group criterion. The treatment included chemotherapy, radiotherapy and surgery accordingly. The association of prognosis with the disease characters, treatment strategy of 98 patients RMS was analyzed by Chi-square test and Kaplan-Merier analysis with SPSS 20.0 software. Results There were 53 boys (54.1％) and 45 girls (45.9％) with a median age of 70 months (2-161 months). There were 43 cases of orbit RMS(43.9％), 46 cases of paramenigneal RMS (46.9％)and 9 cases of non-paramenigneal and non-orbit RMS(9.2％). Twenty seven patients were classified as low risk (27.6％), 42 patients as medium risk (42.9％),and 29 patients as high risk (29.5％). The patients were followed up for a medium of 42 months (9-149 months), 37 cases were dead, 60 cases were survival, and 1 lost the follow-up. Kaplan-Merier survival analysis showed that the overall survival (OS) was 61.9％(60/97), and the average survival time was (92.3±6.9) months. Univariate analysis showed that the OS of patients with paramenigneal RMS was poorer than that of patients with orbit RMS, non-paramenigneal and non-orbit RMS. The OS of high risk RMS patients was poorer than that of intermediate and low risk patients (χ2=6.132, P=0.047). Conclusions The prognosis of head and neck RMS in children is generally good, but the prognosis of paramenigneal RMS and high-risk RMS is significantly declined. The primary site of paramenigneal and high risk are independent risk factors for the prognosis of head and neck RMS in children.

Floating needle therapy for postoperative functional rehabilitation in patients with surgical neck fracture of humerus: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the effect of floating needle therapy on myofascial trigger point (MTrP) and conventional electroacupuncture on the recovery of shoulder joint function after surgical neck fracture of humerus on the basis of drugs and rehabilitation training.@*METHODS@#A total of 72 patients with unilateral surgical neck fracture of humerus were randomly divided into a floating needle group (35 cases) and an electroacupuncture group (37 cases). At the same time of the basic treatment, both groups were intervened on the 2nd day after operation. Touched the MTrP at the affected limb, and the floating needle was used to sweep around it in the floating needle group. In the electroacupuncture group, electroacupuncture was applied at Hegu (LI 4), Quchi (LI 11), Waiguan (TE 5) on the affected side, the dilatational wave (4 Hz/20 Hz) was selected. The treatment was given once every day for 2 weeks. Pain visual analogue scales (VAS) score, constant shoulder joint score, and changes in the number of MTrP were used to evaluate the pain and functional status of the shoulder joints before, after treatment, and 3 months after treatment.@*RESULTS@#Compared with that before treatment, the VAS scores were decreased, the constant scores were increased, and the numbers of MTrP were decreased in the two groups after treatment and 3 months after treatment (<0.05), but the improvement in the floating needle group was better than that in the electroacupuncture group (<0.05). Compared with that after treatment, the VAS scores were decreased and the constant scores were increased 3 months after treatment in the floating needle group (<0.05), and the VAS scores in the electroacupuncture group were decreased (<0.05).@*CONCLUSION@#Floating needle therapy is helpful for the rehabilitation of shoulder joint function after surgical neck fracture of the humerus, and its curative effect is better than conventional electroacupuncture.

Relationship between Blood Acetaldehyde Concentration and Psychomotor Function of Individuals with Different ALDH2 Genotypes after Alcohol Consumption / 法医学杂志

Objective To explore the change rules of blood ethanol and blood acetaldehyde concentration, the impairment of psychomotor functions of different acetaldehyde dehydrogenase （ALDH） 2 genotype individuals after alcohol consumption and the relationship among them. Methods The ALDH2 genotypes in seventy-nine healthy volunteers were obtained by SNaPshotTM method, then divided into ALDH2*1/*1 （wild type） and ALDH2*1/*2 （mutant type） group. After volunteers consumed 1.0 g/kg of alcohol, blood ethanol concentration and blood acetaldehyde concentration at a series of time points before and after alcohol consumption and psychomotor functions, such as, visual selective response time, auditory simple response time and tracking experiment were detected. Biphasic alcohol response questionnaires were collected. Results After alcohol consumption, ALDH2*1/*2 group's blood ethanol and blood acetaldehyde concentration reached the peak earlier than ALDH2*1/*1 group. Its blood acetaldehyde concentration was higher than that of ALDH2*1/*1 group, 1-6 h after alcohol consumption. The psychomotor functions, such as visual selective response time and auditory simple response time in ALDH2*1/*2 group were more significantly impaired than those in ALDH2*1/*1 group after alcohol consumption. There was no statistical significance between the two groups in excitement or sedation reactions （P>0.05）. Pearson correlation coefficient test showed that blood acetaldehyde concentration was related with psychomotor function. Conclusion There are significant differences between the psychomotor function of ALDH2 wild type and mutant type individuals after alcohol consumption estimated to be related to the difference in blood acetaldehyde concentration after alcohol consumption.

β-adrenergic receptor activation promotes cardiac miR-21 expression by paracrine action of IL-6 from fibroblasts / 中国病理生理杂志

AIM:To investigate the regulation ofβ-adrenergic receptor (β-AR) agonist isoproterenol (ISO) on cardiac microRNA-21 (miR-21) expression.METHODS:The primary cultured mouse cardiomyocytes and cardiac fibroblasts were isolated by enzyme digestion and treated with ISO at 10μmol/L for 1, 6, 12, 24 and 48 h.The expression of miR-21 was detected by real-time PCR.The protein levels of p-STAT3 and STAT3 were determined by Western blot, and the concentration of interleukin-6 (IL-6) in the cultured supernatant was measured by ELISA.The cells were transfected with the luciferase reporter gene plasmid p GL3-21PPR containing the miR-21 promoter region, and the luciferase reporter gene assay was used to examine the effect of conditioned medium on the transcriptional activity of miR-21.RESULTS:The medium supernatant produced by ISO on cardiac fibroblasts was used as the conditioned medium, which increased the miR-21 expression in the cardiomyocytes in a time-dependent manner after fibroblasts was treated with ISO (P<0.05).The conditioned medium caused a significant increase in the transcriptional activity of miR-21 in the cardiomyocytes, while24 h and 48 h conditioned medium increased the transcriptional activity by 94.9％and 77.1％, respectively (P<0.01).The concentration of IL-6 in the conditioned medium was significantly increased, and the activity of transcriptional factor STAT3 was enhanced by paracrine action of IL-6 in the cardiomyocytes, which promoted the transcription and expression of miR-21.CONCLUSION:β-AR stimulation induces fibroblast synthesis and expression of IL-6 with paracrine effect on cardiomyocytes, up-regulates the expression of miR-21 in cardiomyocytes by IL-6/STAT3 pathway, and participates in the cardiac remodeling.

Correlation between IN1 gene expression levels and clinical characteristics and prognosis of hepatoblastoma in childhood / 中华实用儿科临床杂志

Objective To study on the mRNA expression level of IN1 gene associated with the clinical efficacy and prognosis of hepatoblastoma(HB) in children and to elucidate the early warning value of IN1 gene for prognosis and chemotherapy sensitivity.Methods Forty HB patients were selected based on primary diagnosis and treated from January 2015 to May 2018 in Tongren Hospital Affiliated to Capital Medical University.The expression level of INI1 gene was detected by using fluorescence immuno-PCR.Clinical data of children with HB were collected,including staging,grouping,risk,efficacy and prognosis of chemotherapy.The relationship between the mRNA expression of IN1 gene and clinical data was analyzed by SPSS 21.0 software.Results (1) Clinical characters:the medium age of 40 HB patients was (30.50 ± 2.39) months,male 29 cases (72.5 ％),and female 11 cases (27.5 ％).There was 1 case (2.5％) of stage Ⅱ HB,13 cases (32.5％) of stage Ⅲ HB,and 26 cases (65.0％) of stage Ⅳ.The low-and intermediate-risk group had 12 cases (30.0％) of HB,and the high-risk group had 28 cases (70.0％) of HB.(2) Clinical efficacy and prognosis:by July 1st,2018,the medium following-up time was (12.2 ± 10.1) months,4 patients (10％) were treated by chemotherapy without surgery,and 36 patients (90％) were treated by surgery.All patients (100％) received chemotherapy.The average cycle of chemotherapy lasted (13.17 ± 0.02).Ten patients were dead and 30 patients survived till following-up.The overall survival (OS) rates were 75％ and the event-free survival rates were 50％ (20 patients with HB).(3) IN1 gene mRNA expression:The average PCR quantitative of IN1 gene mRNA of 40 HB patients (2-△CT) was 0.31 ± 0.70.The average mRNA quantitative of HB patients (2-△CT) with high-risk and low/intermediate-risk group was 0.23 ± 0.43 and 0.48 ± 1.13 (t =6.363,P =0.05).According to histology diagnosis,the average mRNA quantitative of small cell undifferentiated (SCU) type (12 cases)and other type (25 cases) was 0.09 ± 0.11 and 0.43 ± 0.86 (t =4.533,P =0.04).The average mRNA quantitative of patients with or without radical surgery was 0.04 ± 0.03 and 0.34 ± 0.74 (t =2.935,P =0.022).The data of children with poor chemotherapy sensitivity(19 cases)and those sensitive to chemotherapy (21 cases) were 0.03 ± 0.04 and 0.30 ± 0.82,and the difference was statistically significant (t =5.688,P =0.018).Conclusions Poor therapeutic effect results in low mRNA expression of IN1 gene in children of HB.The IN1 gene expression could be an early warning factor for treatment sensitivity and prognosis.

Correlation between IN1 gene expression levels and clinical characteristics and prognosis of hepatoblastoma in childhood / 中华实用儿科临床杂志

Objective@#To study on the mRNA expression level of IN1 gene associated with the clinical efficacy and prognosis of hepatoblastoma(HB) in children and to elucidate the early warning value of IN1 gene for prognosis and chemotherapy sensitivity.@*Methods@#Forty HB patients were selected based on primary diagnosis and treated from January 2015 to May 2018 in Tongren Hospital Affiliated to Capital Medical University. The expression level of INI1 gene was detected by using fluorescence immuno-PCR. Clinical data of children with HB were collected, including staging, grouping, risk, efficacy and prognosis of chemotherapy. The relationship between the mRNA expression of IN1 gene and clinical data was analyzed by SPSS 21.0 software.@*Results@#(1)Clinical characters: the medium age of 40 HB patients was(30.50±2.39) months, male 29 cases (72.5%), and female 11 cases (27.5%). There was 1 case (2.5%) of stage Ⅱ HB, 13 cases (32.5%) of stage Ⅲ HB, and 26 cases (65.0%) of stage Ⅳ. The low-and intermediate- risk group had 12 cases (30.0%) of HB, and the high-risk group had 28 cases (70.0%) of HB.(2)Clinical efficacy and prognosis: by July 1st, 2018, the medium following-up time was (12.2±10.1) months, 4 patients (10%) were treated by chemotherapy without surgery, and 36 patients (90%) were treated by surgery .All patients (100%) received chemotherapy.The average cycle of chemotherapy lasted(13.17±0.02). Ten patients were dead and 30 patients survived till following-up.The overall survival (OS) rates were 75% and the event-free survival rates were 50% (20 patients with HB). (3) IN1 gene mRNA expression: The average PCR quantitative of IN1 gene mRNA of 40 HB patients(2-ΔCT)was 0.31±0.70.The average mRNA quantitative of HB patients (2-ΔCT)with high-risk and low/intermediate-risk group was 0.23±0.43 and 0.48±1.13(t=6.363, P=0.05). According to histology diagnosis, the average mRNA quantitative of small cell undifferentiated (SCU) type (12 cases)and other type (25 cases) was 0.09±0.11 and 0.43±0.86(t=4.533, P=0.04). The average mRNA quantitative of patients with or without radical surgery was 0.04±0.03 and 0.34±0.74 (t=2.935, P=0.022). The data of children with poor chemotherapy sensitivity(19 cases)and those sensitive to chemotherapy (21 cases) were 0.03±0.04 and 0.30±0.82, and the difference was statistically significant (t=5.688, P=0.018).@*Conclusions@#Poor therapeutic effect results in low mRNA expression of IN1 gene in children of HB.The IN1 gene expression could be an early warning factor for treatment sensitivity and prognosis.

The biological functions of cell-to-cell connection over long distance--membrane nanotube / 生理学报

Cell-to-cell connections provide conduits for signal exchanges, and play important functional roles in physiological and pathological processes of multicellular organisms. Membrane nanotubes are common long-distance connections between cells, not only transfer molecule signals and mitochondria, but also cooperate with gap junction and other cell-to-cell communications to transfer signals. During the last decade, there are many studies about membrane nanotubes, which focus on the similarities and differences between membrane nanotubes and other cell-to-cell communications, as well as their biological functions. In the present review, we summarized the latest findings about the structural diversity, the similarities and differences in signal transmission with other types of cell-to-cell communications, and physiological and pathological roles of membrane nanotubes.

Research advances of autonomic nervous system in the regulation of cardiac inflammation / 生理学报

The autonomic nervous system consists of the sympathetic nervous system and the parasympathetic nervous system. These two systems control the heart and work in a reciprocal fashion to modulate myocardial energy metabolism, heart rate as well as blood pressure. Multiple cardiac pathological conditions are accompanied by autonomic imbalance, characterized by sympathetic overactivation and parasympathetic inhibition. Studies have shown that overactive sympathetic nervous system leads to increased cardiac inflammatory reaction. Orchestrated inflammatory response serves to clear dead cardiac tissue and activate reparative process, whereas excessive inflammation may result in pathological cardiac remodeling. Since the discovery of the α7 nicotinic acetylcholine receptor (α7nAChR)-mediated cholinergic anti-inflammatory pathway (CAP), the protective effects of the parasympathetic nervous system in cardiac inflammation have attracted more attention recently. In this review, we summarized the role and underlying mechanisms of the sympathetic and parasympathetic nervous systems in cardiac inflammation, in order to provide new insight into cardiac inflammatory response in cardiovascular diseases.

Prostaglandin E receptors differentially regulate the output of proinflammatory cytokines in myometrial cells from term pregnant women / 生理学报

Prostaglandin (PG) E plays critical roles during pregnancy and parturition. Emerging evidence indicates that human labour is an inflammatory event. We sought to investigate the effect of PGE on the output of proinflammatory cytokines in cultured human uterine smooth muscle cells (HUSMCs) from term pregnant women and elucidate the role of subtypes of PGE receptors (EP, EP, EP and EP). After drug treatment and/or transfection of each receptor siRNA, the concentrations of inflammatory secreting factors in HUSMCs culture medium were detected by the corresponding ELISA kits. The results showed that, PGE increased interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) output, decreased chemokine (c-x-c motif) ligand 8 (CXCL8) output in a dose-dependent manner, but had no effect on IL-1β and chemokine (c-c motif) ligand 2 (CCL-2) secretion of HUSMCs. EP/EP agonist 17-phenyl-trinor-PGE stimulated IL-6 and TNFα whilst suppressing IL-1β and CXCL8 output. The effects of 17-phenyl-trinor-PGE on IL-1β and CXCL8 secretion were remained whereas its effect on IL-6 and TNFα output did not occur in the cells with EP knockdown. The stimulatory effects of 17-phenyl-trinor-PGE on IL-6 and TNFα were remained whereas the inhibitory effects of 17-phenyl-trinor-PGE on IL-1β secretion was blocked in the cells with EP knockdown. Either of EP and EP agonists stimulated IL-1β and TNFα output, which was reversed by EP and EP siRNA, respectively. The inhibitors of phospholipase C (PLC) and protein kinase C (PKC) blocked EP/EP modulation of TNFα and CXCL8 output. PI3K inhibitor LY294002 and P38 inhibitor SB202190 blocked 17-phenyl-trinor-PGE-induced IL-1β and IL-6 output, respectively. The inhibitors of adenylyl cyclase and PKA prevented EP and EP stimulation of IL-1β and TNFα output, whereas PLC and PKC inhibitors blocked EP- and EP-induced TNFα output but not IL-1β output. Our data suggest that PGE receptors exhibit different effects on the output of various cytokines in myometrium, which can subtly modulate the inflammatory microenvironment in myometrium during pregnancy.

RNA-binding protein HuR regulates hsa-let-7c expression by its RNA recognition motif / 生理学报

MicroRNAs (miRNAs) are small noncoding RNAs that control diverse cellular and developmental events through repression of large sets of target mRNAs. miRNAs expressions were mainly regulated at two levels: transcriptional and post-transcriptional. Transcriptional regulation of miRNA-encoding genes produce specific expression patterns of individual miRNA. However, the mechanism of post-transcriptional regulation of miRNAs remains largely unknown. The present study was aimed to clarify whether HuR, an evolutionary conserved AU-rich binding protein, could regulate miRNAs expressions. By means of a computational screen for AUUUA motifs within pri-miRNAs, we found that the downstream of hsa-let-7c but not hsa-miR-21 was enriched of AUUUA motifs. Then we transfected HuR and mutant HuR lacking RNA recognition motif 3 (RRM3) respectively into HEK293T cells. And HuR protein and miRNAs expressions were detected by Western blot and real-time PCR, respectively. The results showed that the overexpression of HuR promoted mature hsa-let-7c expression but not hsa-miR-21 expression. Furthermore, overexpression of HuR deletion mutant lacking RRM3 did not promote hsa-let-7c expression. These results suggest that RRM3 is crucial for HuR mediating mature hsa-let-7c expression. Collectively, these findings proposed a novel role of HuR in biogenesis of miRNAs, possibly by way of post-transcriptional regulation of miRNAs.

Correlation of Genetic Polymorphism, Alcoholic Beverage Type and Ethanol Metabolism / 法医学杂志

Objective To explore the effects of A DH1B and A LDH2 gene polymorphism and type of al-coholic beverage on ethanol metabolism, to provide data support for cases involving the interpretation of ethanol metabolism or back calculation of blood ethanol concentration in forensic practice. Methods A total of 81 volunteers were selected. The genotypes of A DH1B, A DH1C and A LDH2 were obtained by a multiplex SNaPshot genotyping method. Each subject was administered with 1.0 g/kg of alcohol. About 1 mL venous blood was collected before and after the alcohol consumption at 30 min, 45 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h and 8 h, respectively. The concentrations of ethanol and acetaldehyde in blood were determined by headspace gas chromatography. The peak times of blood ethanol concentration (Tmax), the peak mass concentrations of ethanol (Cmax), the area under curve (AUC) of ethanol (AUCethanol), AUCacetaldehyde and ethanol elimination rates (β) were calculated. In order to eliminate the influence of A DH1C, the A DH1C*1/*1 carriers were grouped based on the genotype of A DH1B and A LDH2. The data of each group were evaluated by one-way analysis of variance and pairwise comparison tests were performed by least significant difference method. The gene interactions were evaluated by two-way analysis of variance. Each parameter of three kinds of alcoholic beverage (white wine, red wine and beer) among groups was analysed by variance analysis with randomized block design. Results There were no differences in the value of Tmax and Cmax between the groups with different A DH1B and A LDH2 genotype. The differences in the values of AUCethanol, β and AUCacetaldehyde among some groups carrying different A DH1B and A LDH2 geno-type had statistical significance, while no significant difference was observed in these parameters when one individual taking same dose of different alcoholic beverage type. Conclusion The ethanol metabolism is associated with the related gene polymorphism, which is barely affected by alcoholic beverage type.

Treatment and prognosis analysis of 56 cases of childhood hepatoblastoma in advanced stage with pulmonary metastasis / 中华实用儿科临床杂志

Objective To explore the treatment and prognosis of advanced stage childhood hepatoblastoma with pulmonary metastasis.Methods Fifty-six cases of advanced stage hepatoblastoma with pulmonary metastasis diagnosed through pathology from April 2006 to June 2014 in Department of Pediatrics,Beijing Tongren Hospital Affilia-ted to Capital Medical University were enrolled,among them 33 cases were males and 23 cases were females,and the median age was 2.33 years old(1 month-15 years and 1 month old).The clinical effects of multidisciplinary therapy were analyzed.Results (1)Follow-up studies were conducted till December 2016,in which 21 cases of 56 children achieved complete remission,the complete remission rate was 37.5%(21/56 cases),while 12 cases were partial re-mission and 14 cases were deceased,and the effective rate reached 58.9%(33/56 cases).The follow-up period of 41 children were over 24 months,in which the 2-year free event survival(EFS)rate was 37.5%,2-year overall survi-val(OS)rate was 75.0%,5-year survival rate was 42.4%,and the 95% average survival confidence interval was 35.7-55.9 months.(2)The OS rate of children with small age(≤3 years old)was 88.1%(36/42 cases),the ove-rall prognosis was better than that of >3 years old children(35.7%,5/14 cases)(P=0.003).The survival rate of children with complete tumor resection[OS rate was 89.2%(33/37 cases)]was significantly higher than that of the incomplete excision[OS rate was 47.4%(9/19 cases)],and the difference was statistically significant(P=0.001). The prognosis of epithelial type cases was better than that of other types,and the difference was statistically significant (P<0.05),while the fetal type prognosis was the best,and the difference was statistically significant(χ2=8.56,P=0.014).The growth of alpha fetoprotein was negatively correlated with the clinical efficacy and prognosis(r=-0.468, P=0.023).Conclusions Lung is the most common metastatic site of hepatoblastoma,and the marginal lung metasta-sis is more common.With insidious onset and poor prognosis.Therefore,it should be treated with early diagnosis and multidisciplinary therapy to improve prognosis.

Identification of PTCH1-3'-UTR regulated lncRNAs associated with competing endogenous RNA networks in non-small cell lung cancer cell line / 复旦学报（医学版）

Objective To investgate the effect of PTCH1-3'-UTR on the expression of long noncoding RNAs (lncRNAs) and analyze regulatory networks so as to indicate the function of PTCH1-3'-UTR.Methods We screened PTCH1-3'-UTR regulated lncRNAs in non-small cell lung cancer (NSCLC) by using microarray,and validated the expression by qPCR.To explore the potential mechanisms of these lncRNAs underlying NSCLC progression,we performed GO and KEGG pathway analysis of the dysregulated lncRNAs.We also conducted a bioinformatic analysis in TCGA database to identify the association of PTCH1-3'-UTR regulated lncRNAs and the overall survival of NSCLC patients.Results The expression of seven PTCH1-3'-UTR up-regulated lncRNAs (LOC100507547,FAM41C,DOCK4-AS1,AC009305.1,KLF7-IT1,RP11-749H20.1,LINC01511) were validated by qPCR.The GO and KEGG pathway analysis of the dysregulated lncRNAs indicated that a series of biological progresses were involved in the function of PTCH1-3'-UTR regulated lncRNAs,including transcription,signal transduction,protein transport and translational elongation,and several pathways,such as calcium signaling pathway,Jak-STAT signaling pathway,p53 signaling pathway and insulin signaling pathway.Among the lncRNAs regulating PTCH1-3'-UTR,6 were shown to be associated with the overall survival of NSCLC patients.High expression of lncRNA-CDKN2BAS and FAM66D related to the probability of lower survival,while high expression of lncRNA-LINC00240,LOC400027,ABCC6P2 and FLJ10038 might have a higher probability of survival.Conclusions The study would provide an insight of the function of PTCH1-3'-UTR,and PTCH1-3'-UTR dysregulated lncRNAs may be potential prognostic biomarkers for NSCLC.

Bigelovii A induced autophagy in MCF7 cells by inhibiting mTOR signal pathway / 中国药理学通报

Aim To investigate the effects of Bigelovii A on autophagy and its mechanism.Methods Fluorescence microscope,flow cytometry and Western blot were employed to analyze autophagy.Western blot was used to detect the protein expressions of mTOR pathway.MTT colorimetry was used to assay cell viability after treatment with 3-MA and Bigelovii A or Bigelovii A alone.Results Bigelovii A-treated MCF7 cells displayed a dramatic increase in the number of MDC-labeled vesicles and the expressions of LC3-Ⅱ,indicating cell autophagy.Ⅰt was proved that in MCF7 cells,Bigelovii A inhibited mTOR signaling by decreasing Akt and p-ERK.Consistently,Bigelovii A decreased phosphorylation levels of mTOR,p70S6K (Ser371,Thr389) and 4EBP1 proteins.Inhibiting Bigelovii Ainduced autophagy with the autophagy inhibitor 3-methyladenine significantly decreased cell viability,which suggested that Bigelovii A-induced autophagy played a pro-survival role.Conclusion Bigelovii A is likely to induce autophagy through inhibiting mTOR pathway.

AMP-activated kinase activation inhibits transforming growth factor-β1 production in cardiac fibroblasts via targeting C/EBPβ / 生理学报

AMP-activated protein kinase (AMPK) activation has been shown to protect against fibrosis. However, the underlying mechanism remains unclear. Here we explored the effect of AMPK activation on transforming growth factor-β1 (TGFβ1) production induced by angiotensin II (AngII) in cardiac fibroblasts and the underlying mechanisms. Adult mouse cardiac fibroblasts were isolated. TGFβ1 and AMPK activity were determined by ELISA and Western blots, respectively. Pretreatment of AMPK activator AICAR inhibited TGFβ1 production induced by AngII in cardiac fibroblasts, which was reversed by AMPK inhibitor compound C. Furthermore, bioinformatics predicted a potential CCAAT/enhancer-binding protein β (C/EBPβ) binding site in the promoter region of the mouse Tgfb1 gene. Luciferase reporter with wild type, but not deleted, C/EBPβ binding sites transfection in mouse embryonic fibroblasts showed increased TGFβ1 transcriptional activity induced by AngII, indicating that C/EBPβ mediates AngII-induced TGFβ1 transcript expression. Pretreatment of AICAR inhibited C/EBPβ expression induced by AngII. In conclusion, AMPK activation inhibited TGFβ1 production induced by AngII in cardiac fibroblasts through targeting C/EBPβ. This finding provides a new mechanism underlying the anti-fibrogenic effects of AMPK activation.