TFIIB-related factor 1 (BRF1) is an important transcription factor. It specifically regulates the transcription of RNA polymerase III-dependent genes (RNA Pol III genes). The products of these genes are some small non-coding RNAs, including transfer RNAs (tRNAs) and 5S ribosomal RNAs (5S rRNA). The transcription levels of tRNAs and 5S rRNA vary with changes in intracellular BRF1 amounts. tRNAs and 5S rRNA play a crucial role in determining protein synthesis. Studies have demonstrated that dysregulation of tRNAs and 5S rRNA is closely related to cell growth, proliferation, transformation, and even tumorigenesis. BRF1 is a key factor determining the generation of tRNAs and 5S rRNA. Increasing BRF1 expression enhances cell proliferation and transformation, promoting tumor development. In contrast, repressing BRF1 activity decreases the rates of cell proliferation and transformation, and inhibits tumor growth. High levels of BRF1 are found in the samples of patients suffering from hepatocellular carcinoma, breast cancer, gastric carcinoma, lung cancer, prostate carcinoma, and other cancers. It indicates that high levels of BRF1 are closely related to the occurrence of human cancer and may be a common landmark of tumors. But there is discrepancy in the regulatory mechanisms and signaling pathways of BRF1 overexpression in different cancers. In general, high levels of BRF1 in patients suffering from cancer show short survival period and poor prognosis. However, there is one exception, namely breast cancer. Approximate 80% of cases of breast cancer are estrogen receptor-positive (ER+) and 20% are ER-. The cases with high levels of BRF1 reveal longer survival period and better prognosis after they accepted the hormone treatment by Tamoxifen (Tam), compared to the cases with low level BRF1. It seems like a contradiction. Most of the cases with high levels of BRF1 belong to ER+ status. Tam has been used to treat ER+ cases of breast cancer after diagnosis and surgery. Thus, hormone therapy, such as Tam, is more effective on these patients. This is because, on one hand, that Tam competes with E2 (17β-estradiol) to bind to estrogen receptor α (ERα), but does not dissociate to occupy the receptors, blocking E2 binding to this receptor and inhibiting its biological effects. On other hand, Tam can inhibit the expression of BRF1, leading to a decline of intracellular BRF1 levels. Therefore, the actual levels of BRF1 are lower in the patients with ER+ breast cancer. It appears the prognosis of the high BRF1 expression cases better than that of the low BRF1 expression cases. Myocardial hypertrophy manifests magnification of cardiomyocyte volume rather than number increasing in the postnatal heart. Myocardial hypertrophy is a critical risk factor underlying cardiovascular diseases. No matter how myocardial hypertrophy occur, it will ultimately lead to myocardial dysfunction and heart failure. Hypertrophic growth of cardiomyocytes requires a large amount of protein synthesis to meet its needs of cardiomyocyte growth. Animal models and cell experiments have shown that myocardial hypertrophy stimulates a significant increase in BRF1 expression and transcription of tRNAs and 5S rRNA. Interestingly, elevated levels of BRF1 are found in the myocardium tissues of patients with myocardial hypertrophy. These studies demonstrate that BRF1 indeed plays a critical role in myocardial hypertrophy. In summary, high levels of BRF1 are found in patients suffering from different cancers and myocardial hypertrophy. It implies that BRF1 is a promising biological target of cancer and cardiomyopathy. BRF1 is expected to become a common biomarker for early diagnosis and prognostic observation of different human cancers. It is also an important biomarker for the diagnosis and treatment of cardiomyopathy. BRF1 not only holds an important position in the field of basic medical research but also has great prospects for translational medicine. In the present article, we summarize the progress on studies of BRF1 expressions in cancer and cardiomyopathy, proposes future research directions. It is a new research area. Here, we emphasize the significancy of BRF overexpression in the two huge diseases of human, cancer and cardiomyopathy to raise people's attention to this field.

Background Due to the limited availability of established research models, very few studies addressed the health effects and underlying mechanisms following exposure to diesel exhaust during the initiation of pulmonary respiration. It is highly demanded to elucidate such health effects and underlying mechanisms, so as to exert protective measures during the early stages of life. Objective To evaluate the health effects of diesel exhaust very-early-in-life inhalation in hatchling chicken with a novel chicken embryo air cell inhalation exposure model, and to explore the potential roles of aryl hydrocarbon receptor signaling pathways in the observed effects with a specific aryl hydrocarbon receptor inhibitor. Methods Fertilized chicken eggs were assigned into five groups randomly (15 eggs per group): control group, air control group, aryl hydrocarbon receptor inhibitor (PDM2) group, diesel exhaust group, and diesel exhaust + aryl hydrocarbon receptor inhibitor (PDM2) group. Fertilized eggs were incubated with standard procedure. At embryonic day 17 (ED17), aryl hydrocarbon receptor inhibitor was administered to the corresponding animals. During embryonic day 18-19 (ED18-19), chicken embryos were exposed to diesel exhaust via air cell inhalation, then placed back to incubator until hatch. The air control group received clean air infusion during ED18-19, while the control group did not receive any treatment. Within 24 h post-hatch, 26 hatchling chickens were anesthetized with sodium pentobarbital, subjected to electrocardiography, and sacrificed to harvest tissue samples of heart and lung. Cardiopulmonary toxicities were evaluated by histopathology, and potential changes in the protein expression levels of aryl hydrocarbon receptor pathway molecule cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) and fibrosis-related pathway molecule phosphorylated SMAD family member 2 (pSMAD2) were assessed by Western blotting. The remaining 29 hatchling chickens were reared until two weeks old, and then subjected to identical treatments. Results The inhalation exposure to diesel exhaust at initiation of pulmonary respiration resulted in thickened right ventricular wall (by 220.3% relative to the control group, same hereafter) and elevated heart rate (17.4%) in one-day-old hatchling chickens. Although no remarkable fibrotic lesions were observed at this point, the expression levels of CYP1A1 and phosphorylation levels of SMAD2 in the lung tissues significantly increased (by 81.3% and 71.6%, respectively). Such changes were effectively abolished by the aryl hydrocarbon receptor inhibitor PDM2 pretreatment. In the two-week-old animals, the thickened right ventricular wall (by 339.3%) and elevated heart rate (by 18.9%) persisted, and significant fibrotic lesions were observed in the lung tissue samples under Masson staining. Again, the aryl hydrocarbon receptor inhibitor PDM2 pretreatment effectively abolished such changes. In addition, no statistically significant changes in CYP1A1 expression levels were observed in the two-week-old chicken lung samples, and a remarkable down-regulation of SMAD2 phosphorylation was observed. The aryl hydrocarbon receptor inhibitor PDM2 pretreatment independently decreased the phosphorylation levels of SMAD2 in the two-week-old chicken lung samples. Conclusion Inhalation exposure to diesel exhaust at initiation of pulmonary respiration could result in persistent cardiopulmonary injury in hatchling chickens, and the underlying mechanism might be associated with the regulation of pSMAD2 by the aryl hydrocarbon receptor signaling pathway.

Objective:To investigate the dynamic change of Notch1 expression level on the surface of myeloma cells in patients with multiple myeloma (MM) and its clinical significance.Methods:A total of 38 patients with MM in the Fifth Affiliated Hospital of Sun Yat-Sen University from April 2013 to July 2019 were selected. At the same time, 18 patients with mild iron deficiency anemia were selected as controls. Flow cytometry was used to detect Notch1 expression levels on the surface of myeloma cells for MM patients at the first diagnosis (before the treatment), in remission stage (the time of best effect during the treatment) and in the advanced stage (disease progression), and on the surface of normal plasma cells of the control group. The therapeutic efficacy was analyzed, and the expression levels of Notch 1 were compared among the different stages of MM patients and the control group.Results:Among 38 MM patients, 6 cases (15.8%) had strict complete remission (sCR), 14 cases (36.8%) had complete remission (CR), 10 cases (26.3%) had very good partial remission (VGPR), 6 cases (15.8%) had partial remission (PR), 2 cases (5.3%) died after the first course of treatment. Notch 1 detection was performed in 36 patients. The expression rate of Notch1 on the surface of myeloma cells at the first diagnosis, in remission stage, and in the advanced stage of MM patients and on the surface of normal plasma cells of the control group was (13.1±3.9)%, (2.7±1.2)%, (5.4±1.7)% and (2.1±0.3)%; the difference was statistically significant ( F = 151.4, P < 0.01). The expression rate of Notch1 in MM patients at the first diagnosis and in advanced stage was higher than that in remission stage (all P < 0.01), while the expression rate of Notch1 on the surface of myeloma cells in remission stage was higher than that on the surface of normal plasma cells in the control group ( t = 2.219, P = 0.038). Conclusion:The Notch1 signaling pathway may play an important role in the occurrence and development of MM, and Notch1 detection has a certain guiding significance for the monitoring, treatment and prognosis assessment of MM.

Objective To explore the relationship between the expression of transcription factor ⅡB-related factor 1 (Brf1) and the prognosis of non-small cell lung cancer (NSCLC).Methods Collected 96 cases of NSCLC Surgical specimens and clinical data of patients from January 2013 to August 2015 in our hospital.First of all,we compared the expression of Brf1 in NSCLC tissues and adjacent lung tissues by Western blot and RT-qPCR.Then,Immunohistochemistry was used to detect the expression of Brf1 in NSCLC tissues,and analysis of the relationship between Brf1 expression level and clinical case characteristics.Survival curves were plotted using the Kaplan-Meier method and Log-rank test and multivariate Coxv regression analysis were performed.Results Western blot and RT-qPCR results showed that the expression of Brf1 in NSCLC tissues was significantly higher than that in adjacent lung tissues (P ＜0.01).The positive expression rate of Brf1 in 96 cases of NSCLC was 72.9％.The Brf1 expression level was higher in the poorly differentiated group than in the moderately-highly differentiated group(Mean Rank 62.33 ＞ 43.89,Z =-2.914,P =0.004),and the lymph node metastasis group was higher than the non-metastasis group(Mean Rank 60.34 ＞ 42.58,Z =-3.055,P =0.002),which was independent of patient gender,age,smoking status,tumor size,TNM stage,and pathological type (P ＞0.05).Single-factor survival analysis by Log-rank test showed that the survival rate of Brf1 positive expression group was lower than that of the negative group (x2 =7.560,P ＜0.01).Multivariate analysis of Cox regression model found that Brf1 positive expression (HR =2.043,95％ CI:1.082-3.860) was an independent observational index that affects the prognosis of patients with NSCLC.Conclusion Brf1 is overexpressed in NSCLC tissues,and Brf1 negative expression has a good clinical prognosis,suggesting that Brf1 may be one of the indicators of malignant degree and prognosis of NSCLC.

Objective To evaluate the effect of hyperbaric oxygen (HBO) therapy on postoperative cognitive dysfunction (POCD) in elderly patients undergoing general anesthesia.Methods A total of 112 patients,aged 65-75 yr,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,undergoing elective non-cardiac surgery with general anesthesia,were randomly divided into control group (C group,n =54) and HBO group (n =58).Patients were exposed to hyperbaric oxygen in a hyperbaric oxygen chamber once a day from day 3 to day 12 after surgery in both groups.Pressure was slowly increased to 2 atmosphere absolute within 20 min,pure oxygen was inhaled for 35 min by mask,5 min later pure oxygen was inhaled for another 35 min,oxygen inhalation was then stopped and pressure was slowly increased to 1 atmosphere absolute in HBO group.Patients inhaled air at 1 atmosphere absolute for 70 min in C group.Cognitive function score was assessed using Mini-Mental State Examination,language ability test,visual identification function test,digit span backwards task and Hasegawa's Dementia Scale (HDS) at 2 days before surgery and 7 and 13 days after surgery.The development of POCD was recorded.Results Compared with the baseline at 2 days before surgery,language ability test,digit span backwards task and HDS scores were significantly decreased at 7 and 13 days after surgery in C group,and digit span backwards task scores were significantly decreased at 7 days after surgery in HBO group (P＜0.05 or 0.01).The language ability test and HDS scores were significantly higher,and the incidence of POCD was lower at 7 and 13 days after surgery in HBO group than in C group (P＜0.05).Conclusion HBO therapy can reduce POCD in elderly patients undergoing general anesthesia.

Objective To observe the human papillomavirus(HPV) prevalence and its distribution character among females in Changzhou and to provide epidemiological data for the prevention of cervical cancer and development of HPV vaccine .Methods The clinical material consisted of 32215 women ,who were from Changzhou Hospital T .C .M ,Changzhou Maternal and Child Health Care ,The Second People's Hospital of Changzhou and Changzhou Wujin Hospital from January 2014 to June 2016 .17 kinds of high-risk subtypes (HPV16 ,18 ,31 ,33 ,35 ,39 ,,45 ,51 ,52 ,53 ,56 ,58 ,59 ,66 ,68 ,73 ,82) and 6 kinds of low-risk subtypes (HPV6 ,11 ,42 ,43 ,81 ,83) were detected .All cases were divided into six groups according to the age (<20 ;>21 to 30;31 to 40 ;41 to 50 ;51 to 60 ;and>61) and the age distribution of women infected with HPV and genotypes of HPV were analyzed .Results Out of 32215 cervical cell specimens ,8396 cases were detected HPV infections with the position rate of 26 .06% .In seventeen types of high-risk HPV ,HPV 16 (4 .55% ) were the most common subtype ,followed by 52 (4 .43% ) ,58 (2 .75% ) ,53 (2 .42% ) ,51 (2 .16% ) ,68 (1 .85% ) ,56 (1 .73% ) ,33 (1 .40% ) ,18 (1 .38% ) ,66 (1 .33% ) ,59 (1 .26% ) ,39 (1 .08% ) ,31 (1 .02% ) ,35 (0 .89% ) ,45 (0 .42% ) ,73 (0 .26% ) ,and 82 (0 .15% ) .Six types of low-risk HPV were detected ,of which HPV 81 (2 .96% ) was the most common subtypes ,followed by 43 (1 .86% ) ,42 (1 .62% ) ,6 (1 .27% ) ,11 (0 .80% ) and 83 (0 .26% ) .Conclusion The predominant genotypes of HPV 16 and ,52 infection in female reproductive tract are the highest .

The levels of the products of RNA polymerase Ⅲ-dependent genes(Pol Ⅲ genes),including tRNAs and 5S rRNA,are elevated in transformed and tumor cells,which potentiate tumorigenesis.TFIIB-related factor 1(Brf1)is a key transcription factor and specifically regulates the transcription of Pol Ⅲ genes.In vivo and in vitro studies have demonstrated that a decrease in Brf1 reduces Pol Ⅲ gene transcription and is suf-ficient for inhibiting cell transformation and tumor formation.Emerging evidence indicates that dys-regulation of Brf1 and Pol Ⅲ genes is linked to the development of hepatocellular carcinoma(HCC)in humans and animals.We have reported that Brf1 is overexpressed in human liver cancer patients and that those with high Brf1 levels have shorter survivals.This review summarizes the effects of dysregu-lation of these genes on HCC and their regulation by signaling pathways and epigenetics.These novel data should help us determine the molecular mechanisms of HCC from a different perspective and guide the development of therapeutic approaches for HCC patients.

BACKGROUND:As the high proliferation and low apoptosis of the bone marrow in polycythemia vera patients, hematopoietic stem cels transplanted into NOD/SCID mice can differentiate into erythroid cels, but whether hematopoietic stem cels transplantation could improve the hematopoietic function of aplastic anemia mice is not yet reported. OBJECTIVE:To investigate whether transplantation of bone marrow mononuclear cels with JAK2V617F mutation from polycythemia vera patients can influence hematopoietic reconstruction in aplastic anemia mice. METHODS:Severe aplastic anemia mouse models were established by using recombinant human interferon-γplus busulfan, and then, these mouse models were randomly divided into experimental group (n=10) and control group (n=10). Bone marrow mononuclear cels isolated from polycythemia vera patients with positive JAK2V617F mutation were transplanted into the mice in the experimental group via tail vein at 5 days after drug withdrawal.The same volume of normal saline was administered to the control group. Routine peripheral blood test, morphology of bone marrow cels, bone marrow biopsy, and percentage of CD45+ cels in the peripheral blood and marrow were determined at 14 days after transplantation. RESULTS AND CONCLUSION: At 14 days after transplantation, pancytopenia occurred in the experimental group, bone marrow smears showed scattered lymphocytes and hematopoietic progenitors, and bone marrow biopsy presented that hematopoietic tissues were reduced and a smal amount of granulocyte cels and erythroblasts could be seen, but megakaryocytes were rare. In contrast to the control group, there was no improvement in the hematopoietic function of mice in the experimental group. CD45+ cels were detectable in the peripheral blood and bone marrow in the experimental group, but not in the control group; and a higher percentage of CD45+ cels was measured in the bone marrow than in the peripheral blood of experimental group mice. Experimental findings indicate that bone marrow mononuclear cels from polycythemia vera patients with positive JAK2V617F mutation can be engrafted into aplastic anemia mice, but cannot improve the hematopoietic function of mice.

Objective To investigate the relationship between Hepatitis B patients with different viral loads and immunoglob-ulin A,G,M and complement C3,C4.Methods Firstly,followed by real-time fluorescence quantitative PCR detection 210 cases of hepatitis B patients with HBV-DNA levels,according to 10n copies/ml different viral load detection results,it was divided into 102 ~108 copies/ml of the experimental groups.Then the experimental groups and control group were simulta-neously detected in immunoglobulin A,G,M and complement C3,C4.Analysed the correlation between HBV loads and im-munoglobulin A,G,M and complement C3,C4.Results When the viral loads of hepatitis B patients were 105 ~108 copies/ml,the testing results of IgA,IgG and IgM were both increasing (U =12.43,10.96,6.42,P <0.01),while C3 and C4 were both decreasing (U =8.37,6.0,P <0.01).When the viral loads of hepatitis B patients were 102 ~ 104 copies/ml,only IgA and IgM were increasing (U =2.36,2.04,P <0.05),the other testing results had no statistical significance.Between the test of 7 experimental groups compared with each other,only 104 group and 105 group had significantly changed (IgA and IgM were increasing,C4 was decreasing,U =2.39,2.46,2.09,P <0.05,IgG was increasing,U = 3.25,P <0.01),but between other low viral loads or high viral loads were not significantly differences.Conclusion The different viral loads of hepatitis B patients could cause the different changes of immunoglobulin A,G,M and complement C3,C4,especially in the 4 groups from 105 to 108 copies/ml.Followed by increasing in viral loads,there were immunoglobulin A,G,M increasing and comple-ment C3,C4 decreasing,and also serious impaction on the immune function of organism.There was a positive correlation be-tween viral loads in vivo and immune damages,correlation coefficient (γ =0.967,P <0.01).When the viral loads from 104 to 105 copies/ml,the testing results had changed significantly.It suggest that should control viral loads under 104 copies/ml in the hepatitis B antiviral treatment,so the effect of immune function damage will be the minimum.

AIM:To observe the effect of plumbagin on the mRNA and protein expression of nicotinamide ade -nine dinucleotidephosphate oxidase 4 ( Nox4 ) , reactive oxygen species ( ROS ) level and protein expression of α-smooth muscle actin (α-SMA) in the HSC-LX2 cells stimulated with transforming growth factor β1 (TGF-β1) in vitro.METH-ODS:HSC-LX2 cells were cultured in vitro and divided into blank group, model group, high-, medium-and low-dose (2, 1.5 and 1 μmol/L) plumbagin groups .After incubated with each drug for 72 h, the mRNA expression of Nox4 was detec-ted by RT-PCR.ROS levels were tested by in situ loading probe method.The protein contents of Nox4 and α-SMA were measured by Western blot .RESULTS:Compared with model group , after treated with plumbagin for 72 h, the mRNA ex-pression of Nox4, ROS level and α-SMA protein were significantly decreased in high-and medium-dose plumbagin groups (P<0.01).CONCLUSION:Plumbagin inhibits the activation of HSC-LX2 cells via decreasing the expression of Nox4, thus decreasing ROS levels .