Adult ; Aged ; Female ; Humans ; Laryngeal Neoplasms ; diagnosis ; surgery ; Male ; Middle Aged ; Neoplasms, Muscle Tissue ; diagnosis ; surgery

The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.
Animals ; Apoptosis ; Aurora Kinase A ; antagonists & inhibitors ; Cell Cycle Checkpoints ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Colonic Neoplasms ; pathology ; Humans ; Protein Kinase Inhibitors ; pharmacology ; Receptors, Vascular Endothelial Growth Factor ; metabolism ; Xenograft Model Antitumor Assays

OBJECTIVETo observe the anti-inflammatory effect of total saponins of Panax japonicus on LPS-induced RAW264. 7 macrophages.

METHODThe effect of total saponins of P. japonicus of different concentrations on RAW264. 7 cell viability was determined with the MTT method. The NO kit assay was adopted to detect the NO release of total saponins of P. japonicus to LPS-induced RAW264. 7 cells. The enzyme linked immunosorbent assay (ELISA) was used to detect the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin 1-beta (IL-1beta). The reverse transeriptase-polymerase chain reaction (RT-PCR) was used to determine the expression of inducible nitric oxide synthase (iNOS) ,TNF-alpha,IL-1beta. The protein expression of nuclear transcription factor-kappaB p65 (NF-kappaB p65) was tested by Western blot.

RESULTThe safe medication range of total saponins of P. japonicus was less than 80 mg x L(-1). Compared with the LPS model group, total saponins of P. japonicus high, middle and low dose groups (0.1, 1, 10, 40 mg x L(-1)) could significantly reduce the secretion of NO, TNF-alpha, IL-1beta of LPS-induced RAW264. 7 cells, and inhibit the expressions of iNOS, TNF-alpha and IL-1beta mRNA and the protein expression of NF-kappaB p65.

CONCLUSIONThis study preliminarily proves the protective effect of total saponins of P. japonicus on LPS-induced RAW264.7 macrophages. Its action mechanism may be related to NF-kappaB signal pathway.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Inflammation ; drug therapy ; genetics ; immunology ; Interleukin-1beta ; genetics ; immunology ; Lipopolysaccharides ; adverse effects ; Macrophages ; drug effects ; immunology ; Mice ; NF-kappa B ; genetics ; immunology ; Nitric Oxide ; immunology ; Nitric Oxide Synthase Type II ; genetics ; immunology ; Panax ; chemistry ; Protective Agents ; pharmacology ; Saponins ; pharmacology

Glomerular hypertrophy is the main pathological characteristic in the early stage of diabetic nephropathy (DN), and its regulatory mechanism is closely related to mammalian target of rapamycin (mTOR) signaling pathway activity. mTOR includes mTOR complex 1 (mTORC1) and mTOR complex 2(mTORC2), in which, the upstream pathway of mTORC1 is phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase(Akt)/adenosine monophosphate activated protein kinase(AMPK), and the representative signaling molecules in the downstream pathway of mTORC1 are 4E-binding proteins(4EBP) and phosphoprotein 70 S6Kinase(p70S6K). Some Chinese herbal extracts could improve cell proliferation via intervening the expressions of the key molecules in the upstream or downstream of PIK/Akt/mTOR signaling pathway in vivo. As for glomerular mesangial cells(MC) and podocyte, mTOR plays an important role in regulating glomerular inherent cells, including adjusting cell cycle, energy metabolism and matrix protein synthesis. Rapamycin, the inhibitor of mTOR, could suppress glomerular inherent cell hypertrophy, cell proliferation, glomerular basement membrane (GBM) thickening and mesangial matrix deposition in model rats with DN. Some Chinese herbal extracts could alleviate glomerular lesions by intervening mTOR signaling pathway activity in renal tissue of DN animal models or in renal inherent cells in vivo and in vitro.
Animals ; Diabetic Nephropathies ; drug therapy ; enzymology ; genetics ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Hypertrophy ; drug therapy ; enzymology ; genetics ; pathology ; Kidney Glomerulus ; drug effects ; metabolism ; pathology ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; genetics ; metabolism

OBJECTIVETo evaluate clinical effect and safety of floating needle therapy and duloxetine in treating patients with persistent somatoform pain disorder (PSPD).

METHODSTotally 108 PSPD patients were randomly assigned to the floating needle treatment group, the duloxetine treatment group, and the placebo treatment group, 36 in each group. Patients in the floating needle treatment group received floating needle therapy and placebo. Those in the duloxetine treatment group received duloxetine and simulated floating needle therapy. Those in the placebo treatment group received the placebo and simulated floating needle therapy. All treatment lasted for six weeks. Efficacy and adverse reactions were evaluated using Simple McGill pain scale (SF-MPQ) and Treatment Emergent Symptom Scale (TESS) before treatment and immediately after treatment, as well as at the end of 1st, 2nd, 4th, and 6th week of treatment, respectively. Hamilton Depression Scale (HAMD, 17 items), Hamilton Anxiety Scale (HAMA) were assessed before treatment and at the end of 1st, 2nd, 4th, and 6th week of treatment, respectively. Patients in the floating needle treatment group and the duloxetine treatment group with the total reducing score rate of SF-MPQ in Pain Rating index (PRI) ≥ 50% after 6 weeks' treatment were involved in the follow-up study.

RESULTS(1) Compared with the same group before treatment, SF-MPQ score, HAMD score and HAMA total scores all decreased in all the three groups at the end of 1st, 2nd, 4th, and 6th week of treatment (P < 0.05, P < 0.01). Besides , each item of SF-MPQ significantly decreased immediately after treatment in the floating needle treatment group (P < 0.01). Compared with the placebo treatment group, SF-MPQ, HAMD, and HAMA total score in the floating needle treatment group significantly decreased after 1, 2, 4, and 6 weeks of treatment (P < 0.05, P < 0.01). SF-MPQ score, HAMD score and HAMA total score in the duloxetine treatment group also significantly decreased after 2, 4, and 6 weeks of treatment (P < 0.05, P < 0.01). (2) There were 3 patients (8.3%) who had adverse reactions in the floating needle treatment group, 17 (50.0%) in the duloxetine treatment group, and 7 (21.2%) in the placebo treatment group. Compared with the placebo treatment group, the incidence of adverse reaction increased in the duloxetine treatment group (χ² = 6.04, P < 0.05). Besides, it was higher in the duloxetine treatment group than in the floating needle treatment group (χ² = 14.9, P < 0.05). (3) There were 19 patients in the floating needle treatment group and 17 patients in the duloxetine treatment group involved in the follow-up study. Compared with 6 weeks after treatment, no significant difference was observed at 3 and 6 months after treatment in the score of SF-MPQ, HAMD, and HAMA in the floating needle treatment group and the duloxetine treatment group. No significant difference was observed between the two groups (P > 0.05). There were 5 patients (29.4%) who had adverse reactions in the duloxetine treatment group, and no adverse reactions were observed in the floating needle treatment group. The adverse reaction rate was significantly different between the two groups (χ² = 4.26, P < 0.05).

CONCLUSIONSFloating needle therapy and duloxetine were effective in treatment of patients with PSPD. However, floating needle therapy could relieve pain more rapidly than duloxetine, with obviously less adverse reactions.

Acupuncture Therapy ; methods ; Analgesics ; therapeutic use ; Anxiety Disorders ; Duloxetine Hydrochloride ; therapeutic use ; Follow-Up Studies ; Humans ; Needles ; Pain ; Pain Management ; methods ; Pain Measurement ; Psychiatric Status Rating Scales ; Somatoform Disorders ; therapy ; Treatment Outcome

OBJECTIVEAfter performed symptom-limited maximum cardiopulmonary exercise testing (CPET) before and after acute alkalized blood, we repeated CPET with pure oxygen.

METHODSFive volunteers, 3hr after alkalizing blood room air CPET, re-performed CPET inhaling from Douglas bag connected with pure oxygen tank. We compared with those of room air CPETs before and after alkalized blood.

RESULTSAfter alkalized blood oxygen CPET had a similar response pattern as those of CPETs before and after blood alkalization. During the CPET, all breath frequency, minute ventilation and tidal volume at each stage were similar to those of CPETs before and after alkalized blood (P > 0.05),except there was a lower peak tidal volume than those of both CPETs and a slightly higher resting minute ventilation only than CPET after alkalized blood (P > 0.05). After alkalized blood, oxygen CPET, all PaO2 and SaO2 and most Hb were lower than those of both CPETs (P < 0.05). The pHa and [HCO3-]a were higher than those of CPET before alkalized blood (P < 0.05); but were not CPET after alkalized blood (P > 0.05). PaCO2 was similar to that of CPET before alkalized blood (P > 0.05), but was lower than that of CPET after alkalized blood at resting and warm-up (P < 0.05); then was similar to both CPETs at anaerobic threshold (P > 0.05); but was higher at peak exercise higher than those of both CPETs (P < 0.01). Oxygen increased 2,3 volunteers' workload and time at AT and peak exercises.

CONCLUSIONRespiratory response pattern to oxygen CPET after alkalized blood is similar to those of both CPETs before and after alkalized blood. The CPET response is dominantly depended upon metabolic rate, but not levels of pHa, PaCO2 and PaO2.

Blood Gas Analysis ; Exercise Test ; Humans ; Oxygen ; Respiratory Physiological Phenomena

OBJECTIVETo evaluate the sedative effect of continuous intravenous infusion of midazolam in treating severe dental phobia.

METHODS31 patients with severe dental phobia were enrolled and all of them had good communication with dentists. Two teeth in each patient were assigned to control group and experiment group seperately. The control group received root canal therapy. The experiment group were sedated by intravenous midazolam and received root canal therapy. The treat dependence and behavior therapy efficacy were evaluated. The vital signs and side effects during treatment were noted.

RESULTSContinuous intravenous infusion of midazolam showed a significant good sedative effect on patients with severe dental phobia. There were statistical difference in the Houpt score and the Frankl score between experiment group and control group (z = -4.846, P = 0.000; z = -4.907, P = 0.000). The total dose of midazolam was (9.58 +/- 3.76) mg, and mean infusion rate was (0.28 +/- 0.06) mg x kg(-1) x h(-1). The blood pressure, heart rate and respiration of experiment group were depressed. But these changes didn't interfere with the completion of the whole treatment. No severe side effects were detected.

CONCLUSIONThe single use of midazolam as an intravenous sedation agent has satisfactory effect on patients with severe dental phobia.

Blood Pressure ; Conscious Sedation ; Dental Anxiety ; Heart Rate ; Humans ; Hypnotics and Sedatives ; Infusions, Intravenous ; Male ; Midazolam

OBJECTIVEBasis on the dynamic changes of the ventilation and arterial blood gas parameters to symptom-limited maximum cardiopulmonary exercise testing (CPET), we further investigate the effect of alkalized blood by drinking 5% NaHCO3 on ventilation during exercise.

METHODSAfter drinking 5% NaHCO3 75 ml (3.75 g) every 5 min, total dosage of 0.3 g/Kg, 5 volunteers repeated CPET. All CPET and ABG data changes were analyzed and calculated. At the same time, CPET and ABG parameters after alkalized blood were compared with those before alkalized blood (control) used paired t test.

RESULTSAfter alkalized blood, CPET response patterns of parameters of ventilation, gas exchange and arterial blood gas were very similar (P > 0.05). All minute ventilation, tidal volume, respiratory rate, oxygen uptake and carbon dioxide elimination were gradually increased from resting stage (P < 0.05-0.001), according to the increase of power loading. During CPET after alkalized blood, ABG parameters were compared with those of control: hemoglobin concentrations were lower, CaCO2 and pHa were increased at all stages (P < 0.05). The PaCO2 increased trend was clear, however only significantly at warm-up from 42 to 45 mmHg (P < 0.05). Compared with those of control, only the minute ventilation was decreased from 13 to 11 L/min at resting (P < 0.05).

CONCLUSIONEven with higher mean CaCO2, PaCO2 and pHa, lower Hba and [H+]a, the CPET response patterns of ventilatory parameters after alkalized blood were similar.

Blood Gas Analysis ; Carbon Dioxide ; Exercise Test ; Humans ; Oxygen ; Oxygen Consumption ; Respiration ; Respiratory Physiological Phenomena ; Tidal Volume

OBJECTIVEUnder the guidance of the holistic integrative physiology medicine, we reanalyzed the data during symptom-limited maximum cardiopulmonary exercise testing (CPET) in order to investigate control and regulatory mechanism of breathing.

METHODSThis study investigated 5 normal volunteers who accepted artery catheter, performed CPET room air. Continuous measured pulmonary ventilation parameters and per minute arterial blood gas (ABG) analysis sample parameters during exercise. All CPET and ABG data changes were standard analyzed and calculated.

RESULTSWith gradually increasing power, minute oxygen uptake(every breath oxygen uptake x respiratory rate = O2 paulse x heart rate) and minute ventilation (tidal volume x respiratory rate) showed nearly linear progressive increase during the CPET(compared with the rest stage, P < 0.05 - 0.001); Minute ventilation increased even more significant after the anaerobic threshold (AT) and respiratory compensation point. PaO2 was increased at recovery 2 minutes (P < 0.05); PaCO2 was decreased after anaerobic threshold 2 minutes (P < 0.05); [H+]a was increased from AT (P < 0.05), and rapidly raised at last 2 minutes, remained high at recovery. Lactate was increased rapidly from AT (compared with resting, P < 0.05); bicarbonate decreased rapidly from AT (compared with resting, P < 0.05) and it's changed direction was contrary to lactic acid.

CONCLUSIONIn order to overcome the resistance of the power during exercise, metabolic rate othe body increased, respiratory change depend upon the change metabolism, and the accumulation of acidic products exacerbated respiratory reactions at high intensity exercise.

Anaerobic Threshold ; Blood Gas Analysis ; Exercise Test ; Healthy Volunteers ; Heart Rate ; Humans ; Oxygen ; Oxygen Consumption ; Pulmonary Ventilation ; Respiration ; Respiratory Physiological Phenomena ; Tidal Volume

OBJECTIVETo investigate the outcome of surgical treatment for gastrointestinal stromal tumor(GIST) and the associated factors.

METHODSA total of 277 patients with GIST underwent primary surgical treatment from January 1990 to February 2010 at the Cancer Center of Sun Yat-sen University. The clinical data were retrospectively reviewed and the pathological examination was reviewed. Follow-up was performed.

RESULTSThere were 176 males and 101 females. The age ranged from 20 to 81 years old (median,57). Location of the tumor included colorectum (n=28),small bowel(n=76), stomach(n=173). All the patients had en bloc resection, including local excision in 98 patients, organ resection in 64, and extended resection in 115. The 5-year survival rates were 83.5%, 71.9%, and 61.9% in the three different procedures, respectively, and the difference was not statistically significant(P>0.05). Cox model showed that the tumor size, recurrence and metastasis were independent risk factors associated with the prognosis in GIST patients(P<0.05).

CONCLUSIONSSurgery remains the major approach for gastrointestinal GIST. Complete resection is the principal treatment. Extensive resection or extended lymph nodes dissection is not associated with improved survival.

Adult ; Aged ; Aged, 80 and over ; Female ; Gastrointestinal Stromal Tumors ; diagnosis ; surgery ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Young Adult