Functions of key genes involved in TGF-β/Smad signaling pathway in progression of pulmonary fibrosis / 环境与职业医学

Background Although transforming growth factor-β (TGF-β)/Smad signaling pathway is important in regulating the occurrence and development of pulmonary fibrosis, the pathogenesis of pulmonary fibrosis remains elusive. Objective To explore the functions of genes associated with TGF-β/Smad signaling pathway in the progression of pulmonary fibrosis. Methods A NIH-3T3 fibroblast model induced by TGF-β1 was established. The experiment samples were divided into a control group and a TGF-β1 treatment group. The control group was exposed to normal saline, while the TGF-β1 treatment group was exposed to 10 ng·mL−1 TGF-β1 for 12 h. The RNAs of the two groups were extracted, sequenced, and analyzed by bioinformatics methods to identify seven key genes in TGF-β pathway, including Dcn, Smad3, Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3. The gene expression levels of five markers [Collagen1α1, Collagen1α2, α-smooth muscle actin (α-SMA), TGF-β1, and TGF-β3] and the seven key genes were detected by quantitative real-time PCR (qRT-PCR). The proteins of the two groups were extracted. The important marker protein expression levels of Smad3, the phosphorylation of Smad3 (P-Smad3), and α-SMA were detected by Western blotting. At the same time, 30 healthy SPF-grade C57BL/6 mice were randomly divided into three groups, with 10 mice in each group: a control group, a SiO2 inhalation exposure group for 28 d (10 mice), and a SiO2 inhalation exposure group for 56 d (10 mice). The mice in the two treatment groups were exposed to a natural SiO2 environment for 4 h per day with a 10-min pause for breathing fresh air at 2 h intervals. The lung tissues of the mice were taken after execution. The changes of pulmonary fibrosis were detected by Masson staining, and mRNAs and proteins were extracted to detect the expression of the above key genes and proteins. Results The expression levels of the five marker genes Collagen1α1, Collagen1α2, α-SMA, TGF-β1, and TGF-β3 were significantly increased in the TGF-β1-induced NIH-3T3 fibroblasts than those in the control group (P < 0.01); the expression levels of P-Smad3 and α-SMA proteins increased significantly (P < 0.01); the expression results of the seven key genes screened in the TGF pathway were that Dcn and Smad3 were obviously down-regulated (P < 0.01), and Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3 were obviously up-regulated (P < 0.01). The changes in gene expression levels of the transcriptome sequencing showed the same trend. The results of Masson staining showed that the content of collagen fibers in the lung tissues also increased in the SiO2 inhalation exposure groups over time. In the mouse experiment, five marker genes were obviously up-regulated compared with the control group (P < 0.01); no obvious change was found in the expression of Smad3 protein, and the expression levels of P-Smad3 and α-SMA were obviously higher in the SiO2 exposure groups than those in the control group (P < 0.01); the expression levels of Dcn and Smad3 showed a down-regulated trend, while the expression levels of Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3 showed an up-regulated trend with the increase of SiO2 inhalation exposure days (P < 0.01). The expression levels of the above five marker genes, three important marker proteins, and seven key genes were consistent with the expression trends of TGF-β1-induced NIH-3T3 fibroblasts. Conclusion The expression levels of pulmonary fibrosis-related marker genes and proteins change significantly in TGF-β1-induced fibroblast cells, and the lung tissues of mice under natural SiO2 inhalation exposure has obvious fibrosis characteristics. Seven genes (Dcn, Smad3, Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3) may be involved in the regulation of pulmonary fibrosis by the TGF-β/Smad signaling pathway.

Characteristic of medication compliance behavior in renal transplantation patients / 中南大学学报(医学版)

OBJECTIVES@#After renal transplantation, patients need to take various immunosuppressant, but the drug compliance is poor. The theory of planned behavior suggests that the past medication behavior and subjective norms of individuals are closely related to medication compliance. This study aims to explore the change of medication compliance behavior and its influenting factors for renal transplantation patients at different stages.@*METHODS@#This study was a prospective longitudinal study. The Basel Assessment of Adherence with Immunosuppressive Medication Scale (BAASIS), Medication Belief Scale, Social Support Scale and Quality of Life Scale were used to dynamically follow up renal transplantation patients at pre-operation and 1-month, 6-month, and 12-month after transplantation.@*RESULTS@#A total of 300 patients completed the whole follow-up. The percentage of patients with good medication compliance was 97.60%, 87.30% and 84.30% at 1-month, 6-month and 12-month after transplantation respectively. The life quality of the patients was decreased at 6 months after the operation, and the patients with better self-reported life quality had poor medication compliance. After adjusting for demographic data, the risk of medication incompliance in patients with poor medication compliance before operation was 37.646 times than those with good compliance. Patients who did not use medication reminders had high risk (odds ratio=2.467) of drug non-adherence. The risk of drug non-adherence in patients with more postoperative misgivings was 1.265 times compared with that in patients with less postoperative misgivings.@*CONCLUSIONS@#The medication compliance decreases with the time of transplantation, but the medication compliance of patients with good self-reported life quality is poor. Medication concerns reduce the compliance behavior. Preoperative medication behavior has a significant predictive effect on postoperative behavior. Medication reminder is a protective factor for promoting compliance. Medical staff should pay more attention to preoperative medication belief, behaviors and reminder of using drug so as to provide precise intervention in the renal transplantation patients.

Application of percutaneous intervention in the treatment of benign biliary-enteric anastomosis stricture / 国际外科学杂志

Choledochojejunostomy is a common surgical method for the treatment of organ diseases such as hepatobiliary, gastrointestinal and pancreatic diseases, but there are many complications related to the operation. Benign biliary-enteric anastomosis stricture (BBES) is the most common long-term complication after operation, which seriously affects the quality of life of patients. At present, bile duct reconstruction and endoscopic treatment are the main methods to deal with BBES, but there are some limitations. The new interventional therapy has the advantages of small trauma, good repeatability, high success rate and few complications. It has been applied in many medical centers. The main treatment methods include percutaneous transhepatic biliary balloon dilatation, percutaneous temporary stent placement, percutaneous transhepatic choledochoscopy, magnetic compression anastomosis and intrabiliary ablation. Up to now, there is no uniform standard for the choice of interventional therapy for BBES at home and abroad, so it is of great clinical significance to establish a standardized interventional therapy strategy.

Circular RNA hsa_circ_0005556 Accelerates Gastric Cancer Progression by Sponging miR-4270 to Increase MMP19 Expression

Purpose@#Circular RNAs (circRNAs) are a new class of RNA molecules whose function is largely unknown. There is a growing evidence that circRNAs play an important regulatory role in the progression of a variety of human cancers. However, the exact roles and the mechanisms of circRNAs in gastric cancer are not clear. In this study, we aimed to elucidate the mechanism of hsa_circ_0005556. @*Materials and Methods@#Real-time quantitative polymerase chain reaction was used to detect the expression of hsa_circ_0005556, miR-4270, and matrix metalloproteinase-19 (MMP19) in gastric cancer tissues and cell lines. The expression of hsa_circ_0005556 in gastric cancer cells was silenced by lentivirus, and cell proliferation, invasion, migration, and tumorigenesis in nude mice were assessed to evaluate the function of hsa_circ_0005556 in gastric cancer. @*Results@#The expression of hsa_circ_0005556 in gastric cancer tissues and gastric cancer cell lines was higher compared to normal controls. In vitro, the downregulation of hsa_ circ_0005556 significantly inhibited proliferation, migration, and invasion of gastric cancer cells. In vivo, the downregulation of hsa_circ_0005556 suppressed tumor growth in nude mice. @*Conclusions@#Our study shows that the hsa_circ_0005556/miR-4270/MMP19 axis is involved in proliferation, migration, and invasion of gastric cancer cells through the competing endogenous RNA (ceRNA) mechanism.

Research progress of valproic acid genomics / 药学实践杂志

Valproic acid is a commonly used and broad-spectrum antiepileptic drug in clinical practice with a narrow therapeutic window. Valproic acid has a great individual difference in its metabolism which is influenced by many factors. The gene polymorphism of drug metabolic enzymes is one of the critical factors. Through consulting relevant articles, the affection of genomics and clinical treatment on valproic acid clinical application were reviewed in this paper, which provided a reference for clinical individualized treatment.

Establishment and characterization of patient derived xenograft model of malignant peritoneal mesothelioma in nude mice / 中华病理学杂志

Objective@#To establish patient derived xenograft (PDX) model of malignant peritoneal mesothelioma (MPM), and to identify the key characteristics of tumor biology of the model, so as to provide an experiment platform for studying the pathologic mechanisms and new therapeutic strategies for MPM.@*Methods@#Surgically excised MPM tumor tissues were inoculated subcutaneously in BALB/c-nu/nu mice for 3 stable passages. In the 4th passage, the subcutaneous tumors were harvested under aseptic conditions, cleaned and made into MPM tumor cell homogenate. Four nude mice (two males and two females) were selected and one male and one female nude mouse were inoculated in the abdominal cavity at the dose of 100 μL, others were inoculated at a dose of 200 μL. The PDX model of MPM was established. The changes of body mass in nude mice were measured regularly, the extent of abdominal and pelvic tumors was judged by experimental peritoneal cancer index (ePCI) score, and the pathologic characteristics of tumors were analyzed.@*Results@#The subcutaneous and abdominal animal models of MPM were successfully established. The subcutaneous tumor model grew into tumor on the 20th day, followed by a slow growth stage between the 20th and 29th day, then a rapid growth stage between the 30th and 57th day. According to the dose of tumor cells (100, 200 μL) and timing (14th and 69th days after grafting), the abdominal tumor model successfully simulated the early and late clinical stages of MPM. The HE staining results of the MPM nude mice model showed that the tumor was epithelial mesothelioma and invaded most of the organs, including liver, spleen, pancreas, mesentery. Immunohistochemical staining for calretinin, cytokeratin 5/6, WT1 and Ki-67 were positive. Whole-genome exon sequencing identified 26 and 36 high frequency gene mutations in tumors derived from the PDX model and clinical sample from patients, including 21 common gene mutations.@*Conclusions@#The PDX model of MPM is established. The model is characterized by highly malignant tumor with rapid growth and high invasiveness.

Influencing factors of no seeking medical treatment among pneumoconiosis patients / 中华劳动卫生职业病杂志

Objective@#To study the causes and influencing factors of no seeking medical treatment among pneumoconiosis patients.@*Methods@#Using stratified sampling method and typical survey method, we carried out the questionnaire survey in nine provinces in China including the east, the medium and the western region using a questionnaire on the seeking medical behavior pf pneumoconiosis patients and the influencing factors. The subjects include occupational pneumoconiosis cases and clinically diagnosed cases and the response rate is 94.3 percent. The data was entered twice with epidate3.1 and error detection and statistical analysis was completed with SPSS 20.0. Chi-square test was used for univariate analysis, and multivariate logistic regression was used for multivariate analysis.@*Results@#One thousand and thirty-seven subjects were investigated with average age 55.9±11.2 years. Seventy percent of them were silicosis and 21.9 percent were coal worker’s pneumoconiosis with 67.5 percent of them residing permanently in the countryside, and 37.9 percent of their education background were primary school culture and 33.1 percent of them had junior high school culture. Thirty two point six percent of respondents had no personal income with a median monthly income of 1 200 yuan. Four hundred and thirty four of subjects hadn't seek medical treatment since they got the pneumoconiosis accounting for 41.9 percent with three hundred and thirty seven of them hospitalized directly. The reasons of no seeking medical treatment for the respondents mainly include the self-induction symptoms lighter, the high cost of treatment and cannot claiming the payment of the medical expenses, buying drugs in drugstore, thinking that no medicine can cure pneumoconiosis or no effect, complex procedures, too far away from medical institutions, no unaccompanied, needing a long time or no time, communication disorders, etc. accounting for 44.4 percent, 24.6 percent, 10.9 percent, 9.1 percent, 6.9 percent, 4.4percent, 3.2 percent, 2.9 percent, 1.9 percent, 1.5 percent, respectively. The results of multivariate analysis showed the main characteristics of subjects with restrictions to the outpatient health service utilization are as follows: demographic sociological indicators such as registered permanent residence area is western (ORwestern=2.18, 95%CI:1.38-3.43) , more than seventy five years old (ORover 75=6.82, 95%CI:2.04-22.9) , unemployment, temporary or permanent employment (OR unemployment=1.90, 95%CI:1.17-3.08; ORtemporary employment=3.11, 95%CI:1.57-6.14; ORpermanent employment=2.10, 95%CI:1.18-3.74) , self-rated health score of 50 or above (ORself-rated-70=2.04, 95%CI:1.18-3.51; ORself-rated-90=3.00, 95%CI:1.97-5.37; ORself-rated 90=2.95, 95%CI:1.74-8.07) ; with increase to the outpatient health service utilization are breath with difficulty (OR=0.57, 95%CI:0.41-0.78) , emphysema (OR=0.48, 95%CI:0.26-0.90) , hospitalized with pneumo-coniosis (OR=0.12, 95%CI:0.07-0.20) .@*Conclusion@#Pneumoconiosis patients no covered by injury insurance should be orderly included in the basic medical security system, and be given the medical treatment actively; It should be strengthened the health management for the pneumoconiosis patients and correctly guided the utilization of medical services.

Pathological prognostic factors of pseudomyxoma peritonei / 中华病理学杂志

Objective@#To analyze the pathological features of pseudomyxoma peritonei (PMP) in correlation with the survival status and independent prognostic factors.@*Methods@#One-hundred and fifty-five PMP specimens were collected at Beijing Shijitan Hospital, Capital Medical University, from 2012 to 2018. Conventional histopathological evaluation was performed to document the primary tumor site, histopathological type, lymph nodes metastasis, tumor emboli in the blood and lymph vessels, nerve invasion and cellular density. The immunohistochemical parameters including Ki-67, p53, MMR-related protein, MUC2 and MUC5AC were analyzed. Clinical follow-up data were reviewed to correlate with pathological prognostic factors using Kaplan-Meier estimator and Cox proportional hazards regression model for univariate and multivariate analysis.@*Results@#Among 155 PMP patients, there were 77 males and 78 females. There were 98 cases (63.2%) of low-grade peritoneal mucinous carcinomatosis, 49 cases (31.6%) of high-grade peritoneal mucinous carcinomatosis, 8 cases (5.2%) of high-grade mucinous carcinoma peritonei with signet ring cells; only 15 cases (9.7%) with lymph node metastasis; 18 cases (11.6%) with tumor emboli in the blood and lymph vessels; 8/126 (6.3%) were positive dMMR; 100 cases (64.5%) had Ki-67 label index <50%, and 56 cases(36.1%) presented with mutant type p53. Univariate analysis revealed 11 survival-related pathological parameters including gender, age, primary tumor site, histopathological type, lymph node metastasis, tumor emboli in the blood and lymph vessels, nerve invasion, cellular density, Ki-67 label index rate, p53 and dMMR. Multivariate analysis identified 4 independent prognostic factors including the histopathological type (HR 59.78, P<0.01), lymph node metastasis (HR 3.74, P=0.028), nerve invasion (HR 7.81, P=0.007) and dMMR (HR 9.82, P<0.01).@*Conclusions@#Histopathological type is the most important prognostic factor of PMP with dMMR as an independent molecular prognostic indicator.

Clinical pathologic characteristics of extranodal follicular dendritic cell sarcoma / 中华肿瘤杂志

Objective@#To investigate the clinical pathologic characteristics of extranodal follicular dendritic cell sarcoma (FDCS).@*Methods@#We collected 7 cases of extranodal FDCS, HE staining, immunohistochemical study were performed. The V600E mutation of BRAF in 7 cases were detected by real-time PCR and EBER in situ hybridization was performed on 4 cases.@*Results@#Among the 7 cases of FDCS, 5 cases were male and 2 cases were female, the median age was 55 years old, including 4 cases of low-grade FDCS and 3 cases of high-grade FDCS. The tumor location of 2 cases was in mediastinum, the tumor locations of others were in nasopharynx, kidney, lung, rectum and liver, respectively. The results of immunohistochemistry showed that, the tumor cells were diffusely or focally positive for CD21, CD23, CD35, D2-40, EGFR and CXCL13, but negative for S-100, CD68, HMB45, SMA, Desmin, CD117, Dog-1, CD34, CD30, EMA and CK.Five cases were positive for PD-L1 and the its expression in high-grade FDCS were higher than that in low-grade FDCS.Two cases of low-grade FDCS were positive for BRAF V600E, but the BRAF V600E mutation weren′t detected in all of 7 cases. The result of EBER in-situ hybridization showed that only the nasopharynx FDCS was positive.The follow-up information of 5 patients were available (7~43 months), 4 patients died and 1 still alive with rectum metastasis.@*Conclusions@#FDCS is a rare malignant disease with relapse and metastatic tendency. The combined applications of the first-line antibodies including CD21, CD23, CD35 and second-line antibodies including D2-40, CXCL13, EGFR are helpful for its diagnosis and differential diagnosis. The high expression of PD-L1 implicates the potential benefit of FDCS patients acquired from immunotherapy.

Significance of HPV and cell cycle related proteins in basaloid squamous cell carcinoma of the larynx / 中华病理学杂志

Objective@#To study the significance of HPV and cell cycle related proteins in basaloid squamous cell carcinoma (BSCC) of the larynx.@*Methods@#Twenty-nine cases of laryngeal BSCC from Beijing Tongren Hospital from January 2005 to December 2011 were reviewed. HPV typing by polymerase chain reaction-reverse dot blot (PCR-RDB) and p53, Ki-67, p16, p21 and cyclin D1 expression by immunohistochemistry were performed. The relationship between these indicators, various pathologic parameters (TNM, tumor size, tumor site and lymph node metastasis) and HPV status was analyzed.@*Results@#There were 27 male and 2 female patients. The median age was 62 years. Lymph node metastasis and supraglottic tumor location were slightly higher than that of "usual" SCC, but not statistically significant (P>0.05). HPV DNA was detected in 27.6% (8/29) of the laryngeal BSCC, and all were HPV16. The expression of HPV was not related to age, alcohol consumption, tumor stage and tumor size. p53 was expressed in 31.0%(9/29) of laryngeal BSCC, and these cases were more likely supraglottic and had lymph node metastases (P<0.05). p16 staining was seen in 24.1% (7/29) of laryngeal BSCC, and these cases showed slightly higher rate of lymph node metastasis compared to p16 negative cases. The expression rates of p21 and cyclinD1 were 27.6% (8/29) and 69.0%(20/29), respectively, which were not related to age, tumor size, stage, lymph node metastasis, smoking and drinking. There were only 3 p16+ /HPV+ cases, which showed higher p21 and Ki-67 index compared to the HPV negative group (P<0.05).@*Conclusion@#Some laryngeal BSCC expresses HPV DNA, possibly indicating an association with HPV; but p16 expression is not a reliable indicator for HPV infection.

Comparison of whole blood indium and the serum indium of the population exposed to the indium / 中华劳动卫生职业病杂志

Objective@#The method was established for the detection of whole blood indium and serum indium. By comparing the results of two samples, it is possible to explore the significance of whole blood indium and serum indium in the population exposed to indium compounds.@*Methods@#According to GBZ/T 295-2017 and GBZ 294-2017, the whole blood and serum samples were diluted 20 times by 0.5% nitric acid solution (including 0.05% Triton X-100) . Under the standard mode of inductively coupled plasma mass spectrometry (ICP-MS) , whole blood indium and serum indium of indirect exposure group, low exposure group and high exposure group in an indium mine were detected with 20 μg/L rhodium standard solution as internal standard.@*Results@#This method has a working range of 0.00~5.00 μg/L and a correlation coefficien t>0.999. The detection limit and quantitative lower limit of whole blood indium were 0.076 μg/L and 0.26 μg/L respectively. Those of serum indium were 0.06 μg/L and 0.20 μg/L accordingly. The recovery rates of serum and whole blood samples were 88.5%~95.6% and 93.0%~101%. Intra batch precisions were 1.3%~4.4% and 1.9%~3.5% and inter batch precision were 2.4%~6.1% and 2.1%~4.6% in two samples. There were no significant differences between whole blood indium and serum indium in indirect exposure group. The serum indium level was lower than the detection limit in 3 cases, while their whole blood indium was only below the quantitative lower limit. However, in other groups whole blood indium level was significantly higher than serum indium level (P<0.05) and even was two-fold in the high exposure group.@*Conclusion@#The detection of whole blood indium is more sensitive than that of serum indium, which can reflect the internal exposure level more accurately in exposure population. Therefore, the whole blood indium is of more important referential value to health examination and poisoning diagnosis in the population exposed to indium and its compounds.

Clinicopathologic characteristics of pseudomyxoma peritonei / 中华病理学杂志

Objective@#To analyze the relationship between clinicopathologic characteristics of pseudomyxoma peritonei (PMP) and its prognosis.@*Methods@#Fifty-two cases of PMP collected from 2012 to 2017 at Beijing Shijitan Hospital, Capital Medical University were reviewed using the diagnostic criteria of WHO 2010. The histopathologic features, including original location, neural invasion and calcification were observed; and the relationship with prognosis was analyzed. Immunohistochemical staining for CK7, CK20 and CDX2 was performed on all cases. ER, PR, and p16 were additionally performed on those without clear origin.@*Results@#Patients′ mean age was 52.0 years, and included 29 males and 23 females. Thirty-two cases were derived from appendix; among them, 23 were low grade and 29 were high grade. Signet ring-cells, neural invasion and calcification were detected in 15, 12 and 9 cases respectively. Neural invasion was associated with adverse prognosis (P=0.025) and signet ring cell morphology (P<0.01). Prognosis was not related to gender, age, original location or grade.@*Conclusion@#Neural invasion is not uncommon in PMP and predicts a bad prognosis.

Stroke mimics and intravenous thrombolysis / 国际脑血管病杂志

In patients with acute stroke-like onset, many are stroke mimics (SMs). The most common cases include epilepsy, migraine, brain tumor, and metabolic disorders. Accurate identification of SMs is very important for intravenous thrombolytic therapy.It reduces unnecessary treatment and risks and avoids the delay of proper treatment.This article reviews the common SMs in venous thrombolysis and how to identify them from clinical manifestations, imaging, and scale assessment.

Analysis of blood lead level of children living around lead-zinc mines / 中华劳动卫生职业病杂志

Objective@#To investigate the blood lead level of children living around lead-zinc mining areas, in order to analyze its distribution features of the population.@*Methods@#In August 2016, three natural villiages around lead-zinc mines were selected randomly as survey sites, which were grouped A, B and C according to each distances from the center field, totally 1 379 children from the three villages were selected by cluster random sampling method as the investigation subjects, and their elbow peripheral vein blood samples were collected to determine the blood lead level by graphite furnace atomic absorption spectrometry. The distribution features of blood lead in different district, gender and age groups were compared and analyzed.@*Results@#The median and quartile range of blood lead were 0.066 and 0.058 mg/L respectively. The blood lead levels of 341 children were esceeding 100 μg/L and that account for 24.73%. The median blood lead showed statistical significant differrnce among three groups (P<0.01) , and the medians from high to low were: 0.075 mg/L (A) , 0.065 mg/L (B) and 0.059 mg/L (C) respectively. The average blood lead of male was higher than that of female (P<0.01) . There was significant difference in blood lead levels among different aged groups (P<0.01) , and the high blood lead rate dicreased with the increase of age (P<0.01) . Results of multivariate logistic regression analysis showed that there was a high risk of excessive lead in the blood lead of boys aged 1-6 years from the center of the area.@*Conclusion@#The blood lead level of children living around lead-zinc mining areas is relatively high. There are difference in district distribution, gender and age.

The design of PBL combined with CBL teaching course for standardized training of clinicians based on the clinical decision thinking mode / 中华医学教育探索杂志

To design teaching course of problem-based learning (PBL) combined with case-based learning (CBL) for standardized training of clinicians based on clinical decision thinking mode (CDTM) of diagnosis and treatment process for primary liver cancer. The CDTM of treatment choice for primary liver cancer is multi-scheme selection model. The general decision rule includes decision condition, action plan and decision tree. For the theoretical study of clinical decision rules, it is suitable to design PBL teaching, but it is suitable to design CBL teaching course for clinical decision-making practice. The teaching course of PBL combined with CBL is conducive to improving the ability of clinicians' clinical decision thinking step by step.

Effects of Epigallocatechin-3-gallate on Oxidative Stress and Inflammatory Factors in the Kidney Tissues of Rats with Paraquat Poisoning / 中国医科大学学报

Objective To investigate the effect of Epigallocatechin-3-gallate(EGCG)on oxidative stress and inflammatory factors in the kidney tissues of rats with paraquat poisoning,and explore the possible mechanism. Methods Rats were randomly divided into control group(group A), paraquat exposure group(group B),paraquat exposure+low dose of EGCG group(group C),and paraquat exposure+high dose of EGCG group (group D)(n=10 in each group). Kidney tissues were harvested and observed by HE staining. The level of creatinine was tested by biochemical detector. Serum oxidative stress and inflammatory factor level were detected by ELISA method. Oxidative stress in kidney tissue was determined by Western blotting and colorimetry. Inflammatory factor level in renal tissue was tested by real-time PCR. Results Kidney damage was observed in rats of groups B,C,and D. Rats in groups C and D showed less renal injury than group B,and high dose of EGCG(group D)enhanced kidney damage compared to the low dose(group C). Compared with group A,rats in the groups C and D showed lower level of 8-isoprostane,creatinine, interleukin-6(IL-6),and tumor necrosis factorα(TNF-α)in serum and malondialdehyde(MDA),3-nitrotyrosine(3-NT),and TNF-αand IL-6 mRNA in renal tissue in rats with paraquat poisoning,and group D showed the lowest mRNA level of inflammatory factor and oxidative stress. Con-clusion EGCG has protective effects on the kidney of rats with paraquat poisoning,and its mechanism may be related to the reduction of oxida-tive stress and inflammatory reaction in the kidney.

Efficacy observation of DA-EPOCH-R protocol for patients with B-cell non-Hodgkin lymphoma / 白血病·淋巴瘤

Objective To evaluate the efficacy and safety of DA-EPOCH-R protocol for patients with B-cell non-hodgkin lymphoma (NHL). Methods 43 patients with B-cell NHL received DA-EPOCH-R protocol, and their efficacy and adverse reactions were analyzed. Results 43 patients received a total of 203 cycles of chemotherapy and the median chemotherapy cycle was 6 (2ˉ8 cycles). 32 patients (74.4%) achieved complete remission (CR) after 2ˉ4 cycles of chemotherapy. A further analysis found that age ≤60 years and>60 years, stageⅠ/Ⅱand stageⅢ/Ⅳ, germinal center B-cell (GCB), non-GCB, double expression lymphoma (DEL) and non-DEL patients had no significant differences (P> 0.05). With a median follow-up of 40 months (9ˉ62 mouths), the overall survival (OS) rate of 1-year and 3-year was 97.6 % and 92.8 % respectively. The major toxicity of DA-EPOCH-R protocol was hematologic toxicity. Other toxicities were mild, and no treatment-related deaths occurred. At the end of follow-up, no secondary tumors were found. Conclusions DA-EPOCH-R protocol is an effective and safe protocol for patients with NHL. The result shows that the curative effect of patients in stageⅢandⅣis similar to the patients in stageⅠandⅡ.

Effect of febuxostat on epithelial-to-mesenchymal transition of kidney tubules, serum interleukin-6 and transforming growth factor β1 in hyperuricemic rats / 中华内科杂志

Objective To observe the effect of febuxostat on epithelial-to-mesenchymal transition (EMT) of kidney tubules and the levels of serum IL-6 nad transforming growth factor (TGF) β1 in hyperuricemic rats.Methods Forty male SD rats were divided into 4 groups:normal control group (NC group),oteracil potassium group (OP group),oteracil potassium with febuxostat group (OF group) and oteracil potassium with benzbromarone group (OB group).Each group had 10 rats and balanced in body weights.To induce hyperuricemia,rats were given oteracil potassium by gastric garage once a day for eight weeks.Rats in OF group and OB group were given either febuxostat or benbromarone starting with oteracil potassium,and rats in NC group was given saline only.Blood samples were taken before,and at the end of 4 and 8 weeks of the treatments and serum uric acid,creatinine,blood usea nitrogen (BUN),IL-6 and TGFβ1 contents were measured at each time point.Renal pathological changes were observed via HE and Masson staining,and the expression of α-SMA and E-cadherin were detected by immunohistochemistry.Results Compared with those in NC group,the levels of serum uric acid,creatinine,BUN,IL-6 and TGFβ1 in the another three groups were increased significantly (all P ＜ 0.01).However,the IL-6 and TGFβ1 contents in OF group were much lower than those in OP group (P ＜0.01).HE and Masson staining showed that OF group had less damage and tubulointerstitial fibrosis than OP group and OB group (P ＜0.01).Moreover,the expression of α-SMA was significantly down-regulated (P ＜ 0.01) and that of E-cadherin was significantly up-regulated in OF group compared with those in OP group.Conclusion Febuxostat treatment significantly inhibited EMT and reduced the levels of IL-6 and TGFβ1 in hyperuricemia rats.

Effects of Luteolinl on the Proliferation and Differentiation in Human Periodontal Ligament Cells / 沈阳医学院学报

Objective:To evaluate the biological effects of Luteolinl on the proliferation and differentiation in human periodontal ligament cells (PDLC) . Methods:MTT, ALP kit and Q-PCR was used to detect the expression of osteogenesis related gene. Results:Luteolinl (100, 10, 1, 0.1, 0.01μmol/L) could increase the proliferation of PDLC, and there were significant differences compared with control group (P<0.05) . The ALP Kit results showed that Luteolinl could increase the ALP actiuty of PDLC (P<0.05) . The Q-PCR results showed that Luteolin could increase the expression of ALP and RUNX2 (P<0.05) . Conclution:At proper concentration,Luteolinl can increase the proliferation and differentiation of PDLC.

Effects of receptor interacting protein (RIP)1 on isoniazid induced hepatocyte necroptosis in mice / 天津医药

Objective To study the relationship between receptor interacting protein (RIP)1 and hepatocyte necropto?sis in isoniazid (INH) induced mouse model. Methods Kunming male mice were randomly divided into three groups. Con?trol group (C) received 0.3 mL of normal saline one time per day. INH group (INH) was injected intraperitoneally INH 100 mg/kg body weight, one time per day. Nec-1+INH group was injected intraperitoneally Nec-1 in 0.1%DMSO and 1 mg/kg body weight one time/12 hours, and INH was injected intraperitoneally at the same dose with that of INH group. All animals were treated for 7 days. Pathological changes of liver tissues were studied by HE staining. RIP1 expression was detected by immunohistochemical, Western blot and real-time PCR analysis. Levels of malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH) and superoxide dismutase (SOD) in liver homogenate were determined by colorimetric method. Re?sults Hepatocytes were arranged orderly in C group. The degeneration and necrosis of hepatocytes were found in Nec-1+INH group, and severe degeneration and necrosis of hepatocytes were found in INH group. Compared with C group, the ex?pression levels of RIP1, ROS and MDA were increased significantly, and the expression levels of GSH and SOD were de?creased significantly in INH group (P<0.05). INH-induced acute liver necroptosis was significantly alleviated after treat?ment with Nec-1. Compared with INH group, the expression levels of RIP1, MDA and ROS were significantly decreased, and the expression levels of GSH and SOD were significantly increased in Nec-1+INH group (P<0.05). Conclusion These re?sults suggest that RIP1 is involved in INH-induced hepatocyte necroptosis in mice. The inhibition of RIP1 expression might be a treatment strategy for prohibition of INH-induced acute liver necroptosis.