OBJECTIVETo investigate the effects of metoprolol on electrophysiology of ischemic and anoxic myocardium in diabetic rats.

METHODSForty Sprague-Dawley (SD) rats were divided into 4 groups: diabetes group; diabetes and ablation of left sympathetic nerve group; diabetes and metoprolol group and sham group. The diabetes model was induced by intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). The ventricular diastolic effective threshold (DET), effective refractive period (ERP), and Ventricular fibrillation threshold (VFT) were measured. The serum concentration of nerve growth factor (NGF) was measured.

RESULTSMetoprolol increased DET of ischemic and anoxic myocardium in diabetic rats. The ablation of the left sympathetic nerve increased VFT of diabetic rats. VFT in metoprolo group was significantly increased compared to diabetes group after ischemia. The concentrations of NGF in diabetic group and metoprolol group were higher than those in sham group. There were no difference in NGF levels between ablation of left sympathetic nerve group and sham group.

CONCLUSIONThe remodeling of sympathetic nerve affects the electrophysiology of ischemic myocardium of diabetic rats. Metoprolol can increase the VFT and decrease the excitation threshold of the ischemic myocardium in diabetic rats.

Animals ; Diabetes Mellitus, Experimental ; physiopathology ; Heart ; drug effects ; physiopathology ; Male ; Metoprolol ; pharmacology ; Myocardial Ischemia ; physiopathology ; Nerve Growth Factor ; blood ; Rats ; Rats, Sprague-Dawley ; Sympathectomy

Abstract: Objective To investigate the efficacy of capreomycin adjuvant therapy for multidrug-resistant pulmonary tuberculosis (MDR-TB) and its effect on quality of life and immune function. Methods Eighty-eight elderly pulmonary tuberculosis patients admitted to Affiliated Hospital of Hebei University from October 2019 to October 2020 were selected and divided into two groups according to the random number table method. The control group (n=44) used 4-6Am-Mfx（Lfx）-Pto-Cfz-Z-Hhigh-dose-E/5 Mfx（Lfx）-Cfz-Z-E, the research group (n=44) used capreomycin on the basis of the control group. The 6-Minute Walk Test (6MWT) measured value/predicted value and quality of life [36-Item Short Form Health Survey Questionnaire (SF-36)] scores, safety evaluation results, chest CT cavity and lesion absorption rate and sputum culture turned negative were compared between the two groups, and the serum procalcitonin (PCT) expression levels and immune function were detected before and after treatment. Results The 6MWT measured value/predicted value of the research group and control group before the treatment were (0.48±0.11) and (0.64±0.13), which were significantly higher than corresponding (0.51±0.12) and (0.58±0.14) after treatment (t=6.23, 2.520, P<0.05), the measured/expected value of 6MWT increased in both groups after treatment. Compared with the same group before treatment, the SF-36 scores for each dimension increased in both groups after treatment (P<0.01). The expression levels of serum PCT in the research group and control group before the treatment were (0.37±0.09) ng/mL and (0.12±0.03) ng/mL versus (0.36±0.11) ng/mL and (0.21±0.06) ng/mL after treatment (t=17.480, 7.940, P<0.01). Compared with the same group before treatment, serum PCT expression levels decreased in both groups after treatment. Compared with the same group before treatment, CD3+, CD4+ and CD4+/CD8+ were elevated in both groups after treatment (P<0.05 or P<0.01); after treatment, CD3+, CD4+, and CD4+/CD8+ were significantly higher in research group compared to the control group (t=4.21, 8.02, 2.04, P<0.05). The absorption rate of chest CT cavity and lesions and negative rate of sputum culture in the research group were 88.64% (39/44) and 81.82% (36/44), which were significantly higher than corresponding 63.64% (28/44) and 61.36% (27/44) in the control group (P<0.05). Conclusions　Capreomycin can improve the quality of life of MDR-TB patients, extend the 6-minute walking distance, and regulate serum PCT expression levels and immune function, to promote the absorption of chest CT cavity and lesions, and sputum culture to turn negative, and the security is acceptable.

BACKGROUND AND OBJECTIVECombined hypoxic cytotoxic drugs and chemoradiotherapy is an important mean of oncotherapy, and Tirapazamine (TPZ) is one of the most remarkable drugs. It has been shown that TPZ has a synergistic effect with radiotherapy on tumor cells, but whether TPZ would down-regulate the expression of the hypoxia-induced genes has not been reported. This study was to investigate the hypoxia-induced mRNA expressions of hypoxia inducible factor-1alpha (HIF-1alpha) and osteopontin (OPN) in human nasopharyngeal carcinoma HNE-1 and CNE-1 cells and the radiosensitization of TPZ, a hypoxia-specific drug, on HNE-1 and CNE-1 cells in vitro.

METHODSThe IC50 values of TPZ for HNE-1 and CNE-1 cells were measured using MTT assay, and the mRNA expressions of HIF-1alpha and OPN in HNE-1 and CNE-1 cells was determined using RT-PCR under aerobic and hypoxic conditions, respectively. The survival rates of HNE-1 and CNE-1 cells treated with or without TPZ at IC10 in the presence or absence of oxygen for 6 h were determined using colony formation assay following exposure to 1-6 Gy of 60Co radiation. The dose-survival curves were plotted and the values of D0, Dq and SER were calculated as a single-hit multitarget model.

RESULTSThe IC50 values of TPZ were 34.81 μmol/L and 35.02 μmol/L in HNE-1 and CNE-1 cells under aerobic condition, and 30.20 μmol/L and 28.48 μmol/L under hypoxic condition, respectively. The expressions of HIF-1alpha and OPN mRNA were reduced by TPZ in HNE-1 cells, but not in CNE-1 cells under hypoxic condition. For the HNE-1 cells, the respective values of D0 and Dq were 0.89 Gy and 0.28 Gy following normoxic irradiation versus 1.47 Gy and 0.44 Gy following hypoxic irradiation. For the CNE-1 cells, the respective values of D0 and Dq were 0.72 Gy and 0.68 Gy following normoxic irradiation versus 0.95 Gy and 0.56 Gy following hypoxic irradiation. The values of D0 and Dq for HNE-1 and CNE-1 cells treated with TPZ under hypoxic condition following irradiation were 0.66 Gy, 0.21 Gy and 0.85 Gy, 0.79 Gy, respectively.

CONCLUSIONTPZ can down-regulate hypoxia-induced expression of HIF-1alpha and OPN mRNA of HNE-1 cells and radiosensitize the HNE-1 cells but not CNE-1 cells, and act as a hypoxia modifier.

Antineoplastic Agents ; pharmacology ; Cell Hypoxia ; Cell Line, Tumor ; Cell Survival ; drug effects ; radiation effects ; Cobalt Radioisotopes ; Down-Regulation ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Inhibitory Concentration 50 ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Osteopontin ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Radiation Tolerance ; drug effects ; Radiation-Sensitizing Agents ; pharmacology ; Triazines ; pharmacology

OBJECTIVE: To determine the effect of continuously compressive pressure (CCP) on the expression of receptor activator of nuclear factor kappa B ligand (RANKL) in human periodontal ligament cells (HPDLCs) and to investigate the role of RANKL in alveolar bone rebuilding during orthodontic tooth movement. METHODS: The primary HPDLCs were isolated from human periodontal ligament by explanting enzymatic digestion with trypsin and collagenase to establish a pressure model. Top-bottom axial pressures (1, 2, and 3 g/cm(2)) were laid on HPDLCs for 0.5, 1.5, 6, 12, 24, and 48 h, respectively. The RANKL expression was identified by the reverse transcription-polymerase chain reaction (RT-PCR) at the mRNA level. RESULTS: The expression of RANKL mRNA significantly increased in a time-dependent manner (P<0.01), so did the value of pressure, especially in the 2 g/cm(2) group (P<0.05). CONCLUSION CCP can up-regulate the expression of RANKL mRNA in human periodontal ligament cells.
Compressive Strength ; Humans ; Periodontal Ligament ; cytology ; metabolism ; RANK Ligand ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Receptor Activator of Nuclear Factor-kappa B ; genetics ; metabolism ; Stress, Mechanical

Objective To investigate the flexibility of both the covered stents specially designed for use in intracranial vasculature and the delivering system in passing through the bone tube and the physiological curves of the cranial internal carotid artery(CICA)to reach the targeted area,the performance (adherence)of the covered stents in occluding vascular wall diseases and the impact on the vascular branches of the covered segment.Methods The covered stents specially designed for use in intracranial vaseulature were used to treat 13 patients with CICA diseases using endovascular techniques.There were 4 huge pseudoaneurysms,4 giant aneurysms,3 small wide-necked aneurysms,1 giant pseudoaneurysm with concurrent internal carotid cavernous fistula(CCF),and 1 CCF.Prior to the detachment of the covered stents,balloon occlusion test(BOT)of the internal carotid artery on the diseased side and whole-brain digital subtraction angiography(DSA)were performed in all the patients.Three to 16 months following procedure,DSA and clinical follow-ups were performed.Results Thirteen patients all tolerated the BOT well with the DSA demonstrating well-opened anterior and posterior communicating arteries.The covered stents and the delivering systems all successfully passed CICA to reach the targeted diseased area,with the diseased segments of the internal carotid artery including C3—C4 in 4 cases,C4—C5 in 4 and C6—C7 in 5.Immediately following the detachment of the covered stents,DSA demonstrated that 7 aneurysms were completely occluded,4 aneurysms had slight endoleak,and 1 CCF had markedly-decreased blood flow through the fistula.In the patient with concurrent pseudoaneurysm and CCF,the pseudoaneurysm disappeared and the blood flow through the fistula was markedly-reduced immediately following the stenting procedure.Apart from one patient with aneurysmal subarachnoid hemorrhage who died due to extensive vascular spasm on the 9th day following the stenting procedure,all the other 12 patients had unobstructed stented vessels on the follow-up DSA images,with 2 demonstrating slight stenosis.In the 6 patients with post-procedure endoleak,DSA showed that the endoleak in 4 patients had disappeared,one endoleak disappeared following the second stenting,and one CCF remained low-flow fistula.There was no sequela related to the occlusion of branches in the covered arterial segment.Conclusion The covered stents specially designed for use in the intracranial vasculature and the delivering system are both flexible enough to pass the tortuous CICA to reach the intracranial diseased artery,and are effective in managing CICA diseases.Further follow-up is still needed to determine the long-term effect of the covered stents,and the adherence of the covered stents needs further investigation.

Objective:To explore the role of sympathetic adrenal medulla system,vascular endothelial function and renin-angiotensin-aldosterone system (RAAS)in the pathogenesis of hypertension caused by obstructive sleep apnea hypopnea syndrome (OSAHS).Methods:A total of 42 OSAHS patients with hypertension (OSAHS + hypertension group)were selected,and they received continuous positive airway pressure (CPAP)treatment for six months.An-other 50 OSAHS patients without hypertension and no received CPAP treatment were regarded as pure OSAHS group.Levels of norepinephrine (NE),24h urine vanillyl mandalic acid (VMA),nitric oxide (NO),endothelin-1 (ET-1),angiotensin Ⅱ (AngII)and aldosterone before and after treatment were compared in OSAHS + hyperten-sion group,and they were compared with those of pure OSAHS group.Results:① Compared with pure OSAHS group and before treatment in OSAHS + hypertension group,there were significant rise in levels of NE [(3.0± 1.4)ng/ml vs.(4.1± 1.7)ng/ml,(3.7 ± 1.5)ng/ml],ET-1 [(56.7 ± 12.6)pg/ml vs.(66.3 ± 14.7)pg/ml, (63.2±13.8)pg/ml],AngⅡ [(38.2±6.7)pg/ml vs.(45.7±8.5)pg/ml,(42.1 ±7.6)pg/ml]and aldosterone [(148±12)ng/L vs.(162±16)ng/L,(154±15)ng/L],and significant reduction in NO level [(63.7±11.8)μmol/L vs.(56.2 ±8.4)μmol/L,(59.1 ±9.3)μmol/L]after treatment in OSAHS + hypertension group,P <0.05 or <0.01,but there was no significant difference in 24h urine VMA level,P >0.05 both;②Compared with before treatment,there were significant reductions in levels of NE,ET-1 and AngII after treatment in OSAHS +hypertension group (P <0.05 or <0.01),but there were no significant difference in levels of 24h urine VMA,NO and aldosterone,P >0.05 all.Conclusion:Sympathetic adrenal medulla system,renin-angiotensin-aldosterone sys-tem and vascular endothelial function may be involved in incidence of hypertension in OSAHS patients.

BACKGROUNDRecent studies have suggested that cancer stem cells are one of the major causes for tumor recurrence due to their resistance to radiotherapy and chemotherapy. Although the highly invasive nature of glioblastoma (GBM) cells is also implicated in the failure of current therapies, it is not clear how glioma stem cells (GSCs) are involved in invasiveness. Rac1 activity is necessary for inducing reorganization of actin cytoskeleton and cell movement. In this study, we aimed to investigate the distribution characteristics of CD133+ cells and Rac1+ cells in GBM as well as Rac1 activity in CD133+ GBM cells, and analyze the migration and invasion potential of these cells.

METHODSA series of 21 patients with GBM were admitted consecutively and received tumor resection in Tianjin Medical University General Hospital during the first half of the year 2011. Tissue specimens were collected both from the peripheral and the central parts for each tumor under magnetic resonance imaging (MRI) navigation guidance. Immunohistochemical staining was used to detect the CD133+ cells and Rac1+ cells distribution in GBM specimens. Double-labeling immunofluorescence was further used to analyze CD133 and Rac1 co-expression and the relationship between CD133+ cells distribution and Rac1 expression. Serum-free medium culture and magnetic sorting were used to isolate CD133+ cells from U87 cell line. Rac1 activation assay was conducted to assess the activation of Rac1 in CD133+ and CD133 - U87 cells. The migration and invasive ability of CD133+ and CD133 - U87 cells were determined by cell migration and invasion assays in vitro. Student's t-test and one-way analysis of variance (ANOVA) test were used to determine statistical significance in this study.

RESULTSIn the central parts of GBMs, CD133+ cells were found to cluster around necrosis and occasionally cluster around the vessels under the microscope by immunohistological staining. In the peripheral parts of the tumors, CD133+ cells were lined up along the basement membrane of the vessels and myelinated nerve fibers. Rac1 expression was high and diffused in the central parts of the GBMs, and the Rac1+ cells were distributed basically in accordance with CD133+ cells both in the central and peripheral parts of GBMs. In double-labeling immunofluorescence, Rac1 was expressed in (83.14 ± 4.23)% of CD133+ cells, and CD133 and Rac1 co-expressed cells were located around the vessels in GBMs. Significantly higher amounts of Rac1-GTP were expressed in the CD133+ cells (0.378 ± 0.007), compared to CD133- cells (0.195 ± 0.004) (t = 27.81; P < 0.05). CD133+ cells had stronger ability to migrate (74.34 ± 2.40 vs. 38.72 ± 2.60, t = 42.71, P < 0.005) and invade (52.00 ± 2.28 vs. 31.26 ± 1.82, t = 30.76, P < 0.005), compared to their counterpart CD133- cells in transwell cell migration/invasion assay.

CONCLUSIONSThese data suggest that CD133+ GBM cells highly express Rac1 and have greater potential to migrate and invade through activated Rac1-GTP. The accordance of distribution between Rac1+ cells and CD133+ cells in GBMs implies that Rac1 might be an inhibited target to prevent invasion and migration and to avoid malignant glioma recurrence.

AC133 Antigen ; Antigens, CD ; metabolism ; Cell Line, Tumor ; Glioblastoma ; metabolism ; pathology ; Glioma ; metabolism ; pathology ; Glycoproteins ; metabolism ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Peptides ; metabolism ; rac1 GTP-Binding Protein ; metabolism

OBJECTIVETo evaluate the efficacy and safety of video-assisted thoracoscopic (VATS) esophagectomy in the treatment of esophageal cancer.

METHODSFrom June 2004 to October 2007, video-assisted thoracoscopic esophagectomy was performed in 36 patients, including 29 men and 7 women with median age of 58.9 years old. The cancer located at upper segment in 5 cases, middle 25 cases and lower 6 cases. VATS approach was used to mobilize the intrathoracic esophagus and stomach was mobilized by open approach. Esophagogastric anastomosis was performed in the left neck.

RESULTSThe mean operative time was 250 minutes (190-330 min) and average time of VATS was 70 minutes. The mean hospital stay was 8.7 days. Mean lymph node harvest was 14.3 nodes. Post-operative complications occurred in 11 patients(30.6%), but no perioperative death occurred.

CONCLUSIONVideo-assisted thoracoscopic esophagectomy is technically feasible and safe with lower morbidity and shorter hospital stay as compared to open procedure, and may replace the open esophagectomy in selected patients.

Esophageal Neoplasms ; surgery ; Esophagectomy ; methods ; Female ; Humans ; Male ; Middle Aged ; Thoracic Surgery, Video-Assisted

Objective Constructing physiological-psycho-social three dimensional aging index system, and scale to provide a basis for evaluating the effects of human aging and anti-aging measures. Methods Evaluation, modification and determination of the second and third level indexed by Delphi and principal component analysis and other methods. The weight of each index was weighted by the analytic hierarchy process, and the reliability and validity were calculated on the basis of the preliminary scale. A large sample of empirical studied to determine the aging of different age groups standardized score distribution table. The best model for judging functional age was sought, based on a variety of biostatistical models. Results The aging scale was constructed by three levels, the first level included 3 indicators, the second level had 10 indicators, the third level included 51 indicators, and adopted by expert certification the national society. 3 184 valid questionnaires were obtained through epidemiological investigation, the average total score of aging was (46.93±11.07) points, and the scores of aging were positively correlated with age(r=0.785, P<0.001). The average scores of aging in each dimension were different and the difference was statistically significant (all P<0.001), and each dimension had significant difference with age. The growth model (R2=0.635) was selected, the curve of the relationship between the score of aging and age was fitted. Conclusions The three-dimensional human aging scale was scientific, feasible, and has good reliability and validity. The empirical results show that the comprehensive score of aging increase with age, and show certain characteristics and laws on the curve.