Objective:To study the expression of MMP1 and TIMP1 in simple and radiation-combined wound healing and their effects on the healing process and tissue remodeling. Methods: A rat model of radiation-combined wound healing was used. Immunohistochemistry and in situ hybridization were performed which enabled the detection of MMP1 and TIMP1 expression in the healing process. Ultrastructural changes were observed with transmission EM. Results: The wound healing process was impaired and delayed. In rats receiving 25 Gy of gamma ray locally the irradiated wounds healed 6 days later than non-irradiated controls. The following changes in MMP1 and TIMP1 expression were found: (1) In the early inflammatory phase and in the period of granulation tissue formation, MMP1 expression in the newly-formed epidermis of irradiated wounds approximated that in the controls. Later, the epidermal expression of MMP1 in radiation wounds was comparatively increased with the delay of the healing process.On days 3 to 14 after wounding, TIMP1 was weakly positive in the proliferating keratinocytes of control wounds and became negative after epidermal covering, whereas no or only slight epidermal expression was detected in radiation wounds before epidermal covering.(2)MMP1 and TIMP　1 expression in radiation wounds was markedlydecreased in fibroblasts　, endotheliocytes and macrophages as compared with the controls. The expression phase was prolonged due to the delay of the healing process.Conclusions:The reduced expression of MMP1 and TIMP1 in granulation tissue retards such important processes as cell migration, angiogenesis and tissue remodeling, thus retarding the healing process. The expression of MMP1 in the newly-formed epidermis may help the process of reepithelialization,but in the late healing period, overexpression of MMP1 and decreased expression of TIMP1 in the epidermis may hinder the establishment of basal membrane and the formation of granulation tissue, and thus affect the matrix remodeling process.

Objective: To study the mutation of ENG, ACVRL1, and SMAD4 genes in one of a family of hereditary hemorrhagic telangiectasia (HHT) and explore its molecular pathogenesis. Methods: A family spectrum of a patient with a clinical diagnosis of HHT was surveyed. Peripheral blood samples from proband and their eldest were collected, and ENG, ACVRL1 and SMAD4 gene analysis was performed by chip capture high-throughput sequencing. The mutation detected was verified by Sanger. Results: 9 of the 71 family members were diagnosed with HHT with the main manifestation of recurrent nasal bleeding. Genetic analysis showed that the proband and the eldest son of ENG gene exon 9 frameshift mutation: c.1502-1503insGG (p.Gly501GlyfsX18) , and mutations in ACVRL1 and SMAD4 genes were not detected. Conclusion: The frameshift mutation c.1502-1503insGG (p.Gly501GlyfsX18) of the ENG gene is the genetic basis for the pathogenesis of this HHT family.
Endoglin ; Exons ; Genetic Testing ; Humans ; Mutation ; Telangiectasia, Hereditary Hemorrhagic

OBJECTIVETo study the relationship between the expression of Bax, Bcl-2 proteins, and apoptosis in radiation compound wound healing of rats.

METHODSApoptosis, Bax and Bcl-2 proteins were estimated by in situ terminal labeling (TUNEL) and immunohistochemical methods.

RESULTS(1) Changes of the apoptosis in wound healing showed three typical characteristics: early occurrence, high frequency and delayed disappearance after radiation to rats when compared with those of simple wound group, which might be an important reason for radiation-induced delayed wound healing. (2) The expression of Bax protein increased evidently with the increment of apoptosis and showed a good corresponding relationship with the apoptotic frequency in the process of wound healing. While the expression of Bcl-2 protein decreased obviously as the apoptosis reached a maximum and showed increasing tendency up to normal level when the apoptosis decreased distinctively.

CONCLUSIONSBax and Bcl-2 proteins play an important role in the apoptotic regulation of radiation compound wound healing in rats.

Animals ; Apoptosis ; radiation effects ; Female ; Gamma Rays ; Immunohistochemistry ; Proto-Oncogene Proteins ; biosynthesis ; genetics ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; Rats ; Rats, Wistar ; Skin ; pathology ; radiation effects ; Wound Healing ; genetics ; radiation effects ; bcl-2-Associated X Protein

OBJECTIVEThis study was designed to evaluate the role of interleukin (IL)-1β in the development of fibrosis in mice exposed to silica.

METHODSThe total of 96 Male C57BL/6 mice were divided into four groups. (1) blank control group, (2) PBS group in which mice were instilled with PBS only, (3) silica + IL-1β mAb group in which mice were instilled with 2.5 mg silica dust and 40 µg anti-IL-1β mAb, (4) silica group in which mice were instilled with 2.5 mg silica dust and 40 µg IgG. The final volume of suspension or PBS instilled into the mouse was 50 µl. At 7, 28 and 84 days after treatment, 8 mice were sacrificed in each group. Then BALF was collected for the count of inflammatory cells and cytokines determination. The lung tissues were collected for the detecting of mRNA levels of fibrogenic molecules.

RESULTSThe collagen deposition induced by silica in the lung tissues was partly inhibited by anti-IL-1β. A intensely pulmonary cytokines such as IL-1β, TNF-α, MCP-1 were induced by crystalline silica exposure, and partly inhibited by anti-IL-1β. The levels of TGF-β and fibronectin in silica exposed mice were significantly elevated than those in control mice at days 28 and 84 after treatment (P < 0.01). And the mRNA levels of TGF-β, collagen I and fibronectin were significantly decreased in silica+IL-1β mAb group when compared with those in silica group at days 7, 28 and 84 (P < 0.01). There was a significant decrease of the ratios of IFN-γ/IL-4 in both silica+anti-IL-1β mAb and silica groups when compared with those in control mice at the above three time points (P < 0.01). However, the IFN-γ/IL-4 ratios in silica+anti-IL-1β group were significantly higher than those in silica group at 7, 28 and 84 days (P < 0.05 or P < 0.01).

CONCLUSIONIL-1β may promote the pulmonary fibrosis in mice exposed to silica.

Animals ; Antibodies, Monoclonal ; pharmacology ; Bronchoalveolar Lavage Fluid ; chemistry ; Collagen Type I ; metabolism ; Disease Models, Animal ; Fibronectins ; metabolism ; Interferon-gamma ; metabolism ; Interleukin-1beta ; metabolism ; physiology ; Interleukin-4 ; metabolism ; Lung ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Pulmonary Fibrosis ; chemically induced ; metabolism ; pathology ; Silicon Dioxide ; toxicity ; Transforming Growth Factor beta ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Objective To investigate the distribution of gene polymorphism of CYP450 2C9 and VKORC1-1639A/G in the Chinese population as well as the difference of genetic polymorphism between Chinese Han population and other ethnic populations.Contribution of CYP2C9 and VKORC1 genotype to the maintenance doses on warfarin was also studied.Methods The genotype and allele frequencies were calculated and compared with those in other populations.One hundred and one patients with stable anticoagulation with warfarin under a target international normalized ratio(INR)of 2.0 to 3.0 were enrolled for studying the relationship between the CYP2C9 and VKORC1 gene polymorphism and the warfarin maintaining dosage.Results CYP450 2C9~*3 + 1075C/A allele frequencies were:AA in 449 cases(92.2%),AC in 36 cases(7.4%)and CC in 2 cases(0.4%),respectively.VKORC1-1639A/G allele frequencies were AA in 415 cases(85.2%),GA in 72 cases(14.8%),but GG in no case(0.0%),respectively.When linear stepwise regression analysis was used to identify factors contributing to warfarin stable dose,the final equation was:ln(D)=0.346 + 0.017(weight)-0.376(CYP450 2C9~*3 + 1075C/A)+ 0.148(VKORC1-1639A/G)-0.002(age)(r=0.827,P=0.02).Conclusion There existed significant gene polymorphism CYP450 2C9~*3 + 1075C/A and VKORC1-1639A/G in the Chinese Han population.Both Gene polymorphisms of CYP450 2C9*3 + 1075C/A and VKORC1-1639A/G were significantly affecting the maintaining dose of warfarin in the Chinese population.

To study the effect of curcumin on signaling pathway of signal transducers and activators of transcription (STAT5) in primary newly-diagnosed chronic myelocytic leukemia (CML) cells, and to explore the clinical significance of curcumin in the treatment of primary CML cells, the cells were randomly divided into 3 groups: normal control group, CML cells group, and curcumin group; the cellular proliferation was assayed by MTT test; the expression of cellular STAT5 mRNA in CML cells was detected by RT-PCR; the activation of STAT5 in CML cell was detected by electrophoretic mobility shift assay (EMSA). The results showed that the cellular proliferation of curcumin group (OD value 0.640 +/- 0.073) was decreased, as compared with that of the CML cells group (OD value 0.856 +/- 0.083, P <0.01). The expression levels of STAT5 mRNA in CML cells group (integral ratio of OD 1.782 +/- 0.156) were significantly greater than that in the normal control group (integral ratio of OD 0.289 +/- 0.025, P <0.01). The expression of STAT5 mRNA in curcumin group (integral ratio of OD 1.398 +/- 0.126) was significantly decreased as compared with that in the CML cells group (P <0.01). The activation of STAT5 was significantly increased in CML cells group (gray value 5323.375 +/- 515.640) as compared with that in the normal control group (gray value 2943.000 +/- 273.377, P <0.01). The activation of STAT5 of curcumin group (gray value 4331.750 +/- 398.035) was significantly decreased as compared with that of CML cells group (P <0.01). It is concluded that the cellular proliferation and the expression of STAT5 mRNA are increased in the primary CML cells. The activation of STAT5 in primary CML cells is markedly enhanced. STAT5 signaling pathway may be involved in the proliferation of primary CML cells. Curcumin can inhibit the cellular proliferation and the expression of STAT5 mRNA, and down-regulate the activation of STAT5 in primary CML cells. Curcumin may be used in treatment of leukemia.
Adult ; Antineoplastic Agents ; pharmacology ; Cell Proliferation ; drug effects ; Curcumin ; pharmacology ; DNA ; metabolism ; DNA-Binding Proteins ; genetics ; metabolism ; Female ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; metabolism ; pathology ; Male ; Milk Proteins ; genetics ; metabolism ; RNA, Messenger ; analysis ; STAT5 Transcription Factor ; Signal Transduction ; drug effects ; Trans-Activators ; genetics ; metabolism

ObjectiveTo investigate the clinicopathological features and prognosis of natural killer (NK)/T cell lymphoma and to analyze its relationship with Epstein-barr virus(EBV). MethodsTotally, 36 cases of cutaneous NK/T cell lymphoma were collected from 2000 to 2010 at the Department of Pathology, Peking University Health Science Center, and classified into primary and secondary groups according to whether there is evidence of extracutaneous involvement within 6 months after diagnosis. Clinicopathological features were analyzed and Epstein-barr virus (EBV) was detected. ResultsOf these 36 cases, 13 (36.1％) were classified as primary cutaneous NK/T cell lymphoma, 20 (55.6％) as secondary, and 3 (8.3％) remained unclassified because of the lack of clinical data. Males were more likely to develop both primary and secondary cutaneous NK/T cell lymphoma than females, but there was no striking difference in sex ratio between the patients with primary and secondary lymphoma (P ＞ 0.05 ). Compared with the patients with primary cutaneous NK/T cell lymphoma, those with secondary cutaneous NK/T cell lymphoma showed a younger median age at onset(43.5 vs. 54 years, P ＜ 0.05), higher prevalence of B symptoms(including fever, night sweat, body weight loss) and multiple skin lesions (P ＜ 0.05 and 0.01, respectively). EBV was positive in 92.3％ (12/13) of the primary lymphoma cases and 85％(17/20) of the secondary lymphoma cases. Moreover, the median survival was 8 months in all the cutaneous NK/T cell lymphoma cases, and was significantly shorter in secondary cases than in the primary cases(6 vs. 18 months, x2 = 6.074, P ＜ 0.05). ConclusionsCutaneous NK/T cell lymphoma is an EBV-associated, clinica]ly aggressive disease entity. Patients with primary cutaneous NI/T cell lymphoma seem to have an older age at onset and a better prognosis as compared with those with secondary cutaneous NK/T cell lymphoma.

Objective:To evaluate the efficacy of somatosensory evoked potential (SEP) monitoring for prevention of deep venous thrombosis (DVT) in lower extremity of patients undergoing spinal surgery.Methods:A total of 120 patients of both sexes, aged 40-70 yr, of American Society of Anesthesiologists physical status ⅠorⅡ, without impairment of coagulation function, undergoing posterior lumbar interbody fusion, were selected and divided into 3 groups ( n=40 each) using the random number table method and envelope method: basic preventive measure group (group A), compression stocking group (group B) and SEP monitoring group (group C). In group B, elastic stockings were worn at 1 h before surgery.SEP monitoring was performed during surgery, and the intensity of current stimulation was 25 mA in group C. The flow velocity of popliteal vein in both lower extremities was measured using color Doppler ultrasound apparatus during surgery.Venous blood samples were taken to measure plasma D-dimer concentrations at 1 day before surgery, at the end of surgery and at 24 h after surgery.The DVT developed in lower extremities was diagnosed by ultrasound method during surgery and within 24 h after surgery. Results:Compared with A and B groups, the blood flow velocity of popliteal vein was significantly increased, and the plasma D-dimer concentration and incidence of DVT developed in lower extremity during surgery were decreased in group C ( P<0.05). Conclusion:SEP monitoring can effectively prevent the occurrence of DVT in lower extremity while it is used as an electrophysiological monitoring of the spinal cord in patients undergoing spinal surgery.

Objective To evaluate the effects of negative pressure suction liquid collector in patients undergoing percutaneous endoscopic interlaminar discectomy.Methods Fifty patients undergoing percutaneous endoscopic interlaminar discectomy from October 2015 to August 2016 were chosen as the control group,while 50 patients receiving the same surgery from September 2016 to February 2017 were chosen as the experimental group.The experimental group was treated with negative pressure suction liquid collector,and the control group was treated with conventional drainage procedure.Water pollution of surgical drape,operator gown and operating room floor,and workload of operating room personnel were evaluated,and rate of intraoperative hypothermia was compared between two groups.Results There were only 3 cases of operator's splashed sleeves in the experimental group,and the water pollution rate of surgical drape,operator gown and operating room floor in the control group was 100％,and the difference was statistically significant (P＜0.01).The workload of circulating nurses for cleaning wet floor and operation assistants for sucking liquid in the experimental group was reduced by 100％ compared to the control group (P＜0.01).The rate of intraoperative hypothermia was 4％ in the experimental group and 22％ in the control group,and the difference was statistically significant (P＜0.05).Conclusion Application of negative pressure suction liquid collector for percutaneous endoscopic interlaminar discectomy can significantly reduce the workload of operating room personnel and pollution of operating room,and the rate of intraoperative hypothermia.

Objective:To explore the application effect of case-based learning (CBL), teaching mode combined with 3D printing in clinical teaching of sacral tumors.Methods:A total of 108 undergraduate interns and standardized residency training students who studied in our hospital from 2017 to 2018 were divided into the CBL teaching group ( n = 53) and the CBL combined with 3D printing teaching group ( n = 55) according to their study time. The combined teaching group used computer tomography (CT) data to reconstruct and print out a 3D model of sacral tumors based on CBL, and performed preoperative teaching on the invasion of the surrounding tissues of the tumor. The scores of the students in the two groups were evaluated respectively, and the students were surveyed by self-identification questionnaire (learning interest, self-learning ability, teamwork ability, comprehensive analysis ability and clinical thinking ability). The t-test (one-sided) was used for comparison between groups using stata 14.0. Results:The score of CBL teaching group (75.90±6.70) was lower than that of CBL combined with 3D printing teaching group (83.60±7.40). In terms of critical thinking ability evaluation, self-learning ability, learning interest, comprehensive analysis ability and clinical thinking ability, the CBL combined 3D printing teaching group was superior to the CBL teaching group, and the difference was statistically significant ( P<0.001). In terms of teamwork ability, there was no statistical difference between the two groups. Conclusion:The CBL teaching mode combined with 3D printing can improve academic performance, students' learning interest and clinical thinking ability of sacral tumors in the teaching of undergraduate interns and standardized residency training students.