BACKGROUND:The level of peripheral erythrocytes in rats is significantly increased under hypoxia exposure,and the proliferation of nucleated erythrocytes in the bone marrow may be one of the direct causes of the increase in peripheral erythrocytes.Previous studies have focused on the effects of factors such as erythropoietin and hypoxia-inducible factor,but little research has been done on related factors such as inflammation and immunity.OBJECTIVE:To study the expression of interleukin-18 in bone marrow nucleated erythrocytes,bone marrow supernatant and peripheral blood of rats after hypoxia exposure,and to explore the possible role of interleukin-18 in the pathogenesis of chronic mountain sickness.METHODS:Sixteen healthy male SD rats were randomly divided into two groups:the experimental group was kept in a hypobaric oxygen chamber at a simulated altitude of 5 000 m for 28 days,and the control group was kept in a laboratory at an altitude of 2 260 m for 28 days.The blood routine tests of the two groups of rats were performed.The proportion of CD71+nucleated erythrocytes in the bone marrow of the two groups of rats was determined by flow cytometry.The expressions of interleukin 18 mRNA and protein in CD71+nucleated erythrocytes in the bone marrow of the two groups of rats were determined by RT-qPCR and western blot assay.The expressions of interleukin 18 protein in the sternum of the two groups of rats were determined by immunofluorescence.The levels of interleukin 18 in the peripheral blood and bone marrow supernatant of the two groups of rats were determined by ELISA.RESULTS AND CONCLUSION:(1)The indexes of erythrocyte count,hemoglobin,hematocrit,and mean hemoglobin content in peripheral blood of the experimental group were higher than those of the control group(P＜0.05).(2)The proportion in bone marrow CD71+erythroblasts was significantly higher in the experimental group than that in the control group(P＜0.05).(3)RT-qPCR results showed that the expression of interleukin 18 mRNA in CD71+nucleated erythrocytes in the bone marrow of rats in the experimental group was significantly higher than that in the control group(P＜0.05).(4)Western blot assay results showed that the expression of interleukin 18 protein in CD71+nucleated erythrocytes in the bone marrow of rats in the experimental group was significantly higher than that in the control group(P＜0.05).(5)The immunofluorescence results showed that the expression of interleukin 18 protein in the sternum of rats in the experimental group was significantly higher than that in the control group(P＜0.05).(6)ELISA results exhibited that the level of interleukin 18 in the serum of rats of the experimental group was higher than that in the control group(P＜0.05),but the level of interleukin 18 in the bone marrow supernatant of rats in the experimental group was lower than that in the control group(P＜0.05).The results indicate that the increased expression of interleukin 18 in bone marrow CD71+erythroblasts and peripheral blood of rats under hypobaric hypoxia may be involved in the proliferation of erythroblasts in bone marrow.

BACKGROUND:The level of peripheral erythrocytes in rats is significantly increased under hypoxia exposure,and the proliferation of nucleated erythrocytes in the bone marrow may be one of the direct causes of the increase in peripheral erythrocytes.Previous studies have focused on the effects of factors such as erythropoietin and hypoxia-inducible factor,but little research has been done on related factors such as inflammation and immunity.OBJECTIVE:To study the expression of interleukin-18 in bone marrow nucleated erythrocytes,bone marrow supernatant and peripheral blood of rats after hypoxia exposure,and to explore the possible role of interleukin-18 in the pathogenesis of chronic mountain sickness.METHODS:Sixteen healthy male SD rats were randomly divided into two groups:the experimental group was kept in a hypobaric oxygen chamber at a simulated altitude of 5 000 m for 28 days,and the control group was kept in a laboratory at an altitude of 2 260 m for 28 days.The blood routine tests of the two groups of rats were performed.The proportion of CD71+nucleated erythrocytes in the bone marrow of the two groups of rats was determined by flow cytometry.The expressions of interleukin 18 mRNA and protein in CD71+nucleated erythrocytes in the bone marrow of the two groups of rats were determined by RT-qPCR and western blot assay.The expressions of interleukin 18 protein in the sternum of the two groups of rats were determined by immunofluorescence.The levels of interleukin 18 in the peripheral blood and bone marrow supernatant of the two groups of rats were determined by ELISA.RESULTS AND CONCLUSION:(1)The indexes of erythrocyte count,hemoglobin,hematocrit,and mean hemoglobin content in peripheral blood of the experimental group were higher than those of the control group(P＜0.05).(2)The proportion in bone marrow CD71+erythroblasts was significantly higher in the experimental group than that in the control group(P＜0.05).(3)RT-qPCR results showed that the expression of interleukin 18 mRNA in CD71+nucleated erythrocytes in the bone marrow of rats in the experimental group was significantly higher than that in the control group(P＜0.05).(4)Western blot assay results showed that the expression of interleukin 18 protein in CD71+nucleated erythrocytes in the bone marrow of rats in the experimental group was significantly higher than that in the control group(P＜0.05).(5)The immunofluorescence results showed that the expression of interleukin 18 protein in the sternum of rats in the experimental group was significantly higher than that in the control group(P＜0.05).(6)ELISA results exhibited that the level of interleukin 18 in the serum of rats of the experimental group was higher than that in the control group(P＜0.05),but the level of interleukin 18 in the bone marrow supernatant of rats in the experimental group was lower than that in the control group(P＜0.05).The results indicate that the increased expression of interleukin 18 in bone marrow CD71+erythroblasts and peripheral blood of rats under hypobaric hypoxia may be involved in the proliferation of erythroblasts in bone marrow.

A 27-year-old male was admitted to the Xijing Hospital in August 2018 due to unprovoked severe thoracodynia with palpitations, shortness of breath and chest tightness. Computed tomography angiography showed a type A aortic dissection. Genetic testing based on next-generation sequencing for 15 genes associated with hereditary aortic diseases and Sanger sequencing validation revealed a heterozygous missense mutation c.998G>T (p.Gly333Val) in the COL3A1 gene. Sanger sequencing verification of family members confirmed that the mutation c.998G>T co-segregated with the patient′s phenotype in this family. That mutation was classified as "likely pathogenic" according to American College of Medical Genetics and Genomics standards and guidelines for genetic variant classification. Carriers of this mutation can be definitively diagnosed with "vascular Ehlers-Danlos syndrome". After the diagnosis was clarified, symptomatic treatment was given to the patient, but the disease progressed rapidly. The patient discontinued treatment and died shortly after being discharged. In this study, we found a new variant in the COL3A1 gene, expanding the mutation spectrum of this gene.

Objective To investigate the effect of γ-aminobutyric acid(GABA)signaling pathway on endoplasmic reticulum(ER)stress and mitochondrial autophagy in septic rats with acute lung injury(ALI).Methods SD rats were randomly grouped into the control(CON)group,the model group,the GABA signaling pathway activator Baclofen group(the Baclofen group),the GABA signaling pathway inhibitor dicentrine group(the BIC group),with 6 rats in each group.The Baclofen group received intraperitoneal injection of 5 mg/kg Baclofen,and the BIC group received intraperitoneal injection of 1 mg/kg BIC,once a day,for two consecutive weeks.The CON group and the model group were injected with an equal amount of physiological saline via intraperitoneal injection.Enzyme linked immunosorbent assay was applied to detect serum levels of superoxide dismutase(SOD)and malondialdehyde(MDA)and levels of cytochrome C(Cyt.C)and Nicotinamide adenine dinucleotide phosphate(NADPH)in bronchoalveolar lavage fluid(BALF).Transmission electron microscopy(TEM)was applied to observe the ultrastructure of lung tissue cells.HE staining was applied to observe the pathological morphology of lung tissue.TUNEL staining was applied to observe the apoptosis of lung tissue.Western blot assay was applied to detect expression levels of GABAAR,GRP78 and CHOP proteins in lung tissue.Results Compared with the model group,the lung swelling,congestion and inflammatory cell infiltration were improved in the Baclofen group,and the lung injury score,MDA content,apoptosis index,Cyt.C and NADPH levels,GRP78,and CHOP protein levels were reduced(P＜0.05).The number of autophagic vacuoles in phagocytic mitochondria,SOD content and GABAAR protein level were increased(P＜0.05),however,the trend of above indicators in the BIC group was opposite to that in the Baclofen group.Conclusion Up-regulation of GABA signaling pathway may have an improvement effect on ALI in sepsis rats.

Objective:To investigate the genetic etiology of a Marfan syndrome pedigree, and the impact of c.4336G>A variant on the splicing process of FBN1 gene.Methods:The proband was admitted to the Department of Cardiovascular Surgery of Xijing Hospital due to thoracic aortic aneurysm and dissection in August 2019. Multiplex PCR and next generation sequencing technology were used to detect 15 genes associated with hereditary aortic diseases in the proband. Then the pathogenic sites were further verified by Sanger sequencing, and above examinations were also performed among the family members of the proband. The effect of the mutation on mRNA splicing was predicted by splicing prediction software. RNAs from peripheral blood cells of the proband and the healthy person were extracted, and the effect of the mutation on mRNA splicing was verified by reverse transcription PCR and Sanger sequencing. The pathogenicity was analyzed by the recommendations from the American College of Medical Genetics (ACMG).Results:The gene panel detected a missense mutation of FBN1 gene (c.4336G>A) in the proband. Sanger sequencing results were consistent with that of panel. Sanger sequencing results showed that 4 family members were carriers of the same variant, and 3 out of the 4 family members presented signs of thoracic aortic aneurysm and dissection. The dbscSNV_ada_score and dbscSNV_rf_score software predicted that this mutation would lead to the occurrence of abnormal splicing of mRNA. The skipping of exon 35 was verified in the subsequent examinations by reverse transcription PCR and Sanger sequencing. The variant was classified as"pathogenic"according to ACMG guideline.Conclusion:FBN1 c.4336G>A mutation can cause the skipping of exon 35, and this might be the genetic mechanistic of severe cardiovascular abnormalities observed in this Marfan syndrome pedigree.

Objective To investigate the association between cumulative exposure blood to pressure (cum BP) and new-onset chronic kidney disease (CKD).Methods In this prospective cohort study,101 510 employees of Kailuan Group receiving annual health examination during 2006 to 2007 were observed.The participants received the second,third,and fourth annual health examinations during 2008 to 2009,2010 to 2011,and 2012 to 2013 year respectively.Their urinary and serum creatinine were tested,and participants with incomplete SBP,DBP data and CKD were excluded.Further excluding those who somehow failed to take annual health examination,with incomplete data,or new-onset CKD 27 809 participants were selected in the analysis.According to cum BP exposure quintile grouping:Q1 ＜ 3.70 scores;Q2:3.70-6.16 scores;Q3:6.17-8.45 scores;Q4:8.46-10.95scores;Q5 ≥ 10.96 scores.Multivariate Logistic regression was used to analyze the association between cum BP level and new-onset CKD by cum BP exposure quintile grouping.Results The rise of cum BP exposure level caused the increased incidence of CKD.The incidences of CKD in the five quintile groups were 2.59％,3.11％,4.19％,5.81％,and 7.73％ respectively (P＜ 0.01).Compared with Q1 group,multivariate logistic regression analysis showed that after the adjustment of age,gender,education,income,smoking,drinking,BMI,FBG,TC,TG,LDL,HDL,UA and CRP,the incidences of CKD gradually increased in the Q2,Q3,Q4,and Q5 cum BP quintile groups,and OR(95％CI) values were 1.08(0.86-1.35),1.26(1.01-1.58),1.57(1.27-1.95),1.78(1.43-2.21) respectively (P for trend ＜0.01).Similar results were obtained in different genders.For each single point increase of cum BP exposure level,the incidence of CKD increased 6％ in the general population (P for trend ＜ 0.01),increased 8％ in male (P for trend ＜ 0.01),and 3％ in female (P for trend=0.12).Conclusion As the cumulative exposure to blood pressure increases,the risk of CKD incidence rises,especially in men.

OBJECTIVETo evaluate the efficacies of different treatments for recurrent cervical lymph nodes and the factors contributing to prognosis in patients with nasopharyngeal carcinoma after radiotherapy.

METHODSClinical data of 79 patients with nasopharyngeal carcinoma after radiotherapy were retrospectively analyzed, and all cases were diagnosed as having recurrent cervical lymph nodes by pathological examination. The factors including sex, age, the interval between completion of radiotherapy and recurrence, rN stage, treatment methods, and the location relationship between recurrent lesion and primary tumor in the neck were analyzed for prognosis. Kaplan-Meier curves, Log-rank test and Cox's proportional hazards regression mode were used in the statistical analysis.

RESULTSThe median recurrence time was 26 months, and the 1- , 3- and 5-year overall survival rates were 77.9%, 53.4% and 39.7%. Cox's proportional hazards regression mode analysis indicated that age, rN stage, treatment methods, and the location relationship between recurrent lesion and primary tumor were significantly prognostic factors.

CONCLUSIONSNeck dissection is superior to re-radiotherapy in treatment of recurrent cervical lymph nodes in nasopharyngeal carcinoma after radiotherapy. The patients younger than 45 years old, in early rN stage and for recurrence in the center region of primary tumor have a better prognosis.

Carcinoma ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes ; pathology ; Nasopharyngeal Neoplasms ; radiotherapy ; Neck ; Neck Dissection ; Neoplasm Recurrence, Local ; surgery ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; Treatment Outcome

Using cheap biomass resources is a hotspot of research on industrial biotechnology. It is difficult for traditional fermentations with single strain to treat so complex components and more impurities, which becomes the key problem in industrialization. In this review, some existing industrial bioprocesses involving microbial consortia were described. Comparison of 1,3-propanediol production by microbial consortia and pure cultures were then introduced and the relationship between cells in microbial consortia were summarized. Finally, the perspective was also addressed to design and apply microbial consortia in the future.

Objective To evaluate complications from two anal stapling operations of anorectal surgery,the procedure for prolapse and hemorrhoids (PPH) and the stapled transanal rectal resection (STARR).Methods The data of 1 276 patients undergoing PPH for hemorrhoids and 149 patients having STARR for ODS from January 2010 to January 2015,in Beijing Chaoyang Hospital were studied.More than six months of follow-up was done.Statistics used included t Test and Chi-square test,Logistic regression analysis.Results Complications of PPH and STARR included hemorrhage in 27 cases (2.1％) vs.3 cases (2.0％);pain in 285 cases (22.3％) vs.6 cases (4.0％);uroschesis in 96 cases (7.5％) vs.12 cases (8.1％);edema in 227 cases (17.8％) vs.16 cases (10.7％);defecatory urgency in 194 cases (15.2％) vs.38 cases (25.5％);anastomotic infection in 17 cases (1.3％) vs.2 cases (1.3％);mild anal incontinence in 11 cases (0.9％) vs.2 cases (1.3％);anastomotic stenosis in 11 cases (0.9％) vs.1 case (0.7％).There was a positive correlation between dry stool,defecatory urgency and hemorrhage after PPH.PPH compared to STARR:The post-operative pain,edema and defecatory urgency and overall complication rate was significantly different (t =26.51,x2 =4.69,x2 =10.38,x2 =37.12,P ＜ 0.05).Conclusions PPH and STARR have rare serious complications and easy to handle.Abnormal defecation such as dry stool and defecatory urgency is an important risk of hemorrhage.

OBJECTIVETo explore the predictive value of high-sensitivity C reactive protein (hsCRP) in middle-aged population during the peripheral arteriosclerosis.

METHODSRandom sampling method was used in the study. In 2006-2007 Kailuan Group health examination of 101,510 employees, using stratified random sampling method to select 5,852 as observational cohort included, in the final with a standard queue 5,440 in December 2009. This study selected to participate in the 2012-2013 health examination cohort as the research object, in accordance with the inclusion criteria ultimately selected survey 3,978, select the epidemiological investigation, physical examination, laboratory testing data analysis. Of the 3 978 subjects, 2,282 were male and 1,696 were female, and the baseline age was (53.80±11.14) years. According to the baseline hsCRP quartile level was divided into four groups for comparison of baseline data, using multiple linear regression analysis between hsCRP and brachial-ankle pulse wave velocity (baPWV). Area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the prediction of hsCRP levels in peripheral arteriosclerosis.

RESULTSWith increase of hsCRP levels, the survey of baseline levels of baPWV showed increasing trend, (1,445.49±300.55), (1,494.46±307.94), (1,547.67±320.34), (1,621.32±342.53) cm/s, respectively. Multiple linear regression results showed that age, by logarithmic transformation of hsCRP (lghsCRP) level, systolic blood pressure and fasting blood glucose for each additional unit, baPWV levels were increased 266.47, 58.00, 5.02, 39.79 cm/s (P<0.001), and BMI for each additional unit, baPWV level decreased 9.52 cm/s (P=0.030). The prediction of hsCRP in peripheral artery showed that lghsCRP level of AUC to 0.59 (95% CI: 0.57-0.61), lower than the age and systolic blood pressure predicted value AUC (95% CI) of 0.69 (0.67-0.71), 0.75 (0.73-0.77), respectively.

CONCLUSIONThe hsCRP level could not predict the peripheral arteriosclerosis alone, and the combined age and systolic blood pressure level could have better predictive value.

Ankle ; Ankle Brachial Index ; Biomarkers ; Blood Flow Velocity ; Blood Pressure ; C-Reactive Protein ; Female ; Humans ; Male ; Middle Aged ; Peripheral Arterial Disease ; Pulsatile Flow