Volume 88  ·   Issue 32  ·  2008

Nitric oxide (NO) and carbon monoxide (CO) have been found to be produced endogenously in the body since the middle of the 1980s. People first realized that small inorganic molecules with simple structure play an important role in the complex regulation of life activities, which created a brand-new research field of "gas signaling molecules", promoted the progress of life science and medicine, and also opened a new idea of "waste gas without waste". In 1998, three American scientists won the Nobel Prize in Physiology or Medicine for their outstanding achievements in NO research.

Objective To investigate the plasma levels of endogenous hydrogen sulfide (H2S), a gasotransmitter, and homocysteine (Hcy) in patients with Alzheimer' s disease ( AD), vascular dementia ( VD), and cerebrovascular disease (CVD) and their role in the pathogenesis of AD and VD. Methods 31 AD patients, 28 VD patients, 20 CVD patients , and 23 normal controls ( NC group) underwent examination of plasma concentrations of H2S and Hcy, mini mental state examination (MMSE), activity of daily living scale (ADL), Hachinski ischemic score (HIS) , and Hamilton's depression scale (HRSD). The severity of AD and VD was evaluated according to the global deterioration scale (GDS). Results (1) The plasma H2S levels of the AD, VD, and CVD patients were (34 ± 7), (36±5), and (37 ± 7) μmol/L respectively, all significantly lower than that of the NC group [ (45±7) μmol/L,all P <0. 01 ]. However, there were no significant differences in the plasma H2S level among the AD, VD, and CVD patients (all P 0. 05). The plasma H2S concentration was negatively correlated the severity of AD. (2)The plasma Hcy levels of the AD, VD, and CVD patients were ( 14. 0 ± 3. 0), ( 16. 0 ± 6. 1 ), and ( 14. 4 ± 4. 9 ) μmol/L respectively, all significantly higher than that of the NC group [ (9.8±2.5) μmoL/L,P <0. 01 ). However, there was no significant difference in the plasma Hcy level among these 3 groups ( all P 0. 05). The plasma Hcy concentration was positively correlated with the severity of AD or VD. Conclusion H2S and Hcy are both involved in the pathogenesis of AD, VD, and CVD, and its alteration in level may be associated with the severity of AD and VD.

Objective To explore the role of hydrogen sulfide (H2S) in acute lung injury (ALI) during endotoxic shock (ES) and its relationship with nitric oxide (NO) and carbon monoxide (CO). Methods Sixty-four adult male SD rats were randomly divided into 4 equal groups: control group injected with normal saline via the caudal vein, lipopolysaccharide (LPS)-treated group injected with LPS to establish ES model, LPS + NariS group injected with LPS and sodium hydrosulfide ( NaHS, an exogenous H2S donor], and LPS + PPG group injected with LPS and polypropylene glycol ( PPG, a H2S synthase inhibitor). The mean artery pressure (MAP) was measured via apolyethylene catheter in the right common carotid artery for 6 h. Then the rats were sacrificed with their lungs taken out to determine the lung water content, lung tissue melonyldialdehyde (MDA), NO, and CO contents, as well as lung tissue cystathionine-γ-lyase ( CSE), myeloperoxidase ( MPO), nitric oxide synthase ( NOS), and heine oxygenase (HO) activities. The H2S content in blood plasma was detected also. Morphological changes of the lung tissues were observed under light microscope and the index of quantitative assessment (IQA) of lung injury was calculated. Immunohistochemistry and Western blotting were used to detect the lung tissue inducible NOS (iNOS) and HO-1 protein expression. Results Compared with the control group, the MAP of the LPS group was significantly lower, the pathological changes in lung tissue was more obvious, and the IQA, lung water content, lung MDA content, lung MPO and CSE activities as well as plasma H2S content were all significantly higher(P0. 05 or P 0. 01 ). Compared to the LPS group, the plasma H2S and lung CSE activity of the LPS + NariS group were higher, the lung injury was more severe, and the MAP was lower. And compared to the LPS group, the MAP of the LPS + PPG group was higher, and the lung injury was milder ( both P0. 05 ). The eNOS activity in the lung tissue of the LPS group was (5.26 ± 0. 25 ) U · mg-1 · prot-1, significantly lower than that of the control group [ (6. 45 ± 0. 42)U · mg-1 · prot-1> ] ; and the iNOS activity and NO content of the LPS group were ( 12.6 ± 0. 6) U · mg-1 · prot-1 and ( 144 ± 25)μmol/L respectively, both higher than those of the control group [ ( 10. 5±0. 7)U ·mg-1 · prot-1 and (68±5)mol/L respectively] ( P 0. 05 or P 0. 01 ). Compared with the LPS group, the lung tissue eNOS activity of the LPS + PPG group was significantly higher, and the iNOS activity [ ( 10. 2 ± 0.4) U· mg-1 · prot-1], iNOS protein expression, and NO content [ ( 74 ± 5 ) μmol/L] were all significantly lower (P0.05 or P 0. 01 ). Compared with the LPS group, the lung tissue eNOS activity of the LPS + NaHS group [ (4. 81 ± 0. 23)U · mg-1 · prot-1] was significantly lower, and the iNOS activity [ (14. 6 ±0. 4) U · mg-1 · prot-1 ], iNOS protein expression, and NO content[ ( 217 ± 18 ) μmol/L] were significantly higher (P0. 05 or P0. 01 ). The lung tissue HO activity[ (173 ± 31 )pkat/g], HO protein expression, and CO content [ (3.63 ± 0. 24) % ] of the LPS group were all significantly higher than those of the control group[(125±22)pkat/g,(2.48±0.33)% ,both P0.05 ] , and the LPS +PPG group[(88 ± 17) pkat/g, ( 2. 98 ± 0. 23 ) %, both P 0. 05 ]. Compared to the LPS group, the lung tissue HO activity [ (263 ± 37 ) pkat/g ], HO protein expression, and CO content [ ( 4. 35 ± 0. 32 ) % ] of the LPS + NaHS group were all significantly higher ( all P0. 05 ). Conclusion The increase of H2S generation participates in the lung tissue injury during ES and this event is related to eNOS activity decrease, iNOS activity increase that causes the production of large amount of NO. H2S up-regulates the HO-1/CO system in the lung tissues during ES, which may be the endogenous compensatory response against the injury.

Objective To investigate the effects of hydrogen sulfide(H2S) on vascular inflammation in pulmonary hypertension induced by high pulmonary blood flow. Methods Forty-four male SD rats were randomly divided into 8 groups: 4-week control group (n =7), 4-week shunt group (n =7), 4-week shunt + propargylglycine (PPG, an endogenous H2S release inhibitor) intraperitoneal injection group ( n = 8), 11-week control group ( n = 7),11-week shunt group ( n = 7 ), and 11-week shunt + sodium hydrosulfide ( NariS, a H2S donor) intraperitoneal injection group ( n = 8). Right ventricular catheterization was used to measure the mean pulmonary arterial pressure (mPAP). Immunohistochemistry was used to detect the expression of inflammatory related factor intercellular adhesion molecule-1 ( ICAM-1 ), and the key molecules of nuclear factor-кB (NF-кB) signal transduction pathway, including NF-кB p65 and inhibitor of NF-кB (IкBα), in the pulmonary artery, and ELISA was used to detect the concentrations of the inflammatory related factors, including ICAM-1, interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) in blood plasma and lung tissues so as to reflect the corresponding inflammatory responsiveness. Results The plasma and lung tissue ICAM-1, IL-8 and MCP-1 contents of the 4-week shunt group were all significantly higher than those of the 4-week control group ( P0.05 or P 0. 01 ). The mPAP of the 4 week shunt + PPG group was (20. 3 ±1.7)mmHg,significantly higher than that of the 4- week shunt group [ ( 16. 2 ± 1.5) mm Hg, P0. 01]. The expression levels of ICAM-1 and NF-кB p65 in the small and median pulmonary artery endothelin cells of the 4-week shunt + PPG group were both significantly stronger than those of the 4-week shunt group (P0. 05 or P 0. 01 ), whereas the expression of IкBα w as weaker than that of the 4-week shunt group (P 0. 05). The plasma IL-8 content of the 4-week shunt + PPG group was ( 148 ± 29 ) μmol/L, significantly higher than that of the 4 week-shunt group [ ( 118 ± 23) μmol/L, P 0. 05 ], and the lung tissue ICAM-1 and MCP-1 levels of the 4-week shunt + PPG group were (27. 3 ± 5.0) μmol/g and ( 12. 9 ± 1.1 ) μmol/g respectively, both significantly higher than those of the 4-week shunt group [ (21.9 ± 2. 1 ) and ( 10. 2 ± 1.4) μmol/g respectively, both P 0. 05 ]. The mPAP and expression levels of ICAM-1 and NF-кB p65 of the large, median, and small pulmonary artery endothelia cells of the 11-week shunt group were all higher than those of the 11-week control group ( P 0. 05 or P 0. 01 ), whereas the expression levels of IкBα were all less obvious (P.05 or P 0. 01 ). The plasma and lung tissue ICAM-1, IL-8, and MCP-1 levels of the 11-week shunt group were all significantly higher than those of the 11-week control group ( all P 0. 01 ). The mPAP of the 11 week shunt + NaHS group was (23.2 ± 3.0 ) mm Hg, significantly lower than that of the 11-week shunt group [ (27.5 ± 1.9) mm Hg, P 0.05]. The ICAM-1 and NF-кB p65 expression levels of large, median, and small pulmonary artery endothelia cells of the 11-week shunt + NariS group were all significantly weaker than those of the 11-week shunt group (P0. 05 or P 0. 01 ), whereas the protein expression levels of IкBα in small and median pulmonary artery endothelia cells of the 11-week shunt + NaHS group were significantly higher than those of the 11-week shunt group ( both P0. 05). The plasma and lung tissue ICAM-1 contents of the 11-week shunt + NaHS group were ( 124 ± 11 ) μmol/L and ( 19.9 ± 2, 5 ) μmot/g, both significantly lower than those of the 11-week shunt group [ ( 154 ± 20) μmol/L and ( 23.9 ± 3.6) μmol/g respectively, both P0.01 ]. The plasma and lung tissue IL-8 contents of the 11-week shunt + NaHS group were (92 ± 11 ) μmol/L and ( 15.0 ± 1.7 ) μmol/g, both significantly lower than those of the 11-week shunt group [ (121 ± 17) μmol/L and (19.0 ± 3.9) μmol/g respectively, both P 0. 01 ]. The lung tissue MCP-1 content of the 11 -week shunt + NaHs group was ( 10. 8 ± 1.6) μmol/g, significantly lower than that of the 11-week shunt group [ ( 13.5 ± 1.4) μmol/g, P <0. 01 ]. Conclusion H2S attenuates the development of pulmonary hypertension induced by high pulmonary blood flow through ameliorating pulmonary vascular inflammation. The inhibitory effect of H2S on the pulmonary vascular inflammation involves elevating IкBαexpression,down-regulating NF-кB p65 expression and then inhibiting the expression of inflammatory related factors.

Objective To investigate the expression of metastasis-associated gene 1 (MTA1) and matrix metalloproteinase 9 (MMP-9) gene in breast carcinoma and the relationship between the expression of these genes and the invasion of breast cancer. Methods Fluorescence quantitative PCR technique was used to detect the mRNA expression of MTA1 and MMP-9 gene among 56 human breast cancer samples. Results The mRNA expression rate of MTA1 was higher in 83.9% ( 47/56 ) of the primary breast cancer tissues compared with the matched normal breast tissues. The mRNA expression of MMP-9 was higher in 85.7% (48/56) of the primary breast cancer tissues compared to the matched normal breast tissues. The over-expression of MTA1 and that of the MMP-9 gene were significantly related with the degree of differentiation,clinical stage, and lymph node metastasis of breast cancer ( all P 0. 05 ). The positive ratio of MTA1 gene is tightly associated with that of MMP-9 gene (P 0. 05). Conclusion The united detection of MTA1 and MMP-9 gene expression predicts the invasion and metastasis of breast cancer and supplies evidence for clinical therapy and judgment of prognosis. MTA1 and MMP-9 will become new targets for gene therapy.

Objective To investigate the changes of interleukin (IL) -6 serum level in patients with acute respiratory distress syndrome (ARDS) and the effects of continuous renal replacement therapy (CRRT) on IL-6 level and its clinical significance. Methods Forty ARDS patients were randomly divided into 2 equal groups: Group A undergoing conventional treatment and Group B receiving conventional treatment plus CRRT at onset of ARDS. Serum IL-6 level was measured by enzyme linked immunosorbent assay (ELISA) at the onset (0 h) and 12, 24, 48, and 72 hours later. Dynamic APACHE Ⅱ score was also evaluated at the time points of 0, 24, 48, and 72 h. The incidence of ventilator-associated pneumonia ( VAP), intensive care unit (ICU) mortality rate, duration of total mechanical ventilation, and ICU stay were assessed. Twenty-five healthy examinees were used as controls. Results The serum IL-6 level of the whole ARDS patients was significantly higher then that of the normal controls ( P 0.01 ), and the serum IL- 6 level of the ARDS patients who died was significantly higher than that of the ARDS patients who survived (P 0.01 ). The IL-6 serum level was correlated well with the APACHE Ⅱ score either in the survival subgroup or the non-survival subgroup ( for the former: r = 0.560 P = 0.008, and for the latter: r = 0.518 P = 0.023). Group B, contrary to Group A, had persistently decreased serum IL-6 levels and APACHE Ⅱ scores at the onset and during the progression of ARDS ( all P 0.05). The incidence of VAP in Group B was 45%, significantly lower than that in Group A (80%, P =0. 022) while the ICU mortality rate didn't differ between the two groups (40% vs 55%, P =0.342). The duration of total mechanical ventilation and ICU stay of the Group B patients who underwent early CRRT were ( 12 ± 5 ) days and ( 16 ± 5 ) days respectively, both significantly shorter than those of Group A patients [ ( 16 ± 5) days, P = 0. 027 and (19 ± 5) days, P = 0. 030 ]. Conclusion The elevated serum IL-6 level in ARDS patients seems to be correlated well with the severity of lung injury, and appears to be a goad market to judge the prognosis of the disease combined with APACHE Ⅱ score. In the early phase of ARDS, CRRT can decrease the high serum level of IL-6, shorten the duration of total mechanical ventilation and ICU stay, and decrease the incidence of VAP. Removal of the circulating proinflammatory cytokines by CRRT may be one of the most vitalmechanisms to treat ARDS.

Objective To investigate the effects of tongxiuluo (TXL) capsule on cardiac ventricle remodeling after acute myocardial infarction (AMI). Methods Seventy AMI patients were randomly divided into 2 equal groups: conventional therapy group treated with conventional Western therapy and TXL treatment group treated with TXL capsule for 6 weeks in addition to the conventional treatment. Cardiac color ultrasound was conducted before and 6 weeks after the treatment to examine the changes of ventricular structure, mass and function. Radioimmunoassay was used to detect the levels of angiotensin Ⅱ ( Ang Ⅱ) and endothelin-1 (ET-1). Results Six weeks later, the left ventricular posterior wall thickness of end- diastolic (LVPWTD), left ventrieular end-systolic dimension( LVESD), and left atrium dimension (LAD) of the TXL group were 0.93 cm ± 0. 09 cm, 3.71 cm ± 0.19 cm, and 3.21 cm±0.29 cm respectively, all lower than those before treatment (0.93 cm±0.09 cm, 3.71 cm ±0. 19 cm, and 3.21 cm±0.29 cm respectively)and those of the conventional treatment group (0.95 cm±0.08 cm, 3.62 cm±0.46 cm, and 3.82 cm±0.30 era) ( all P 0.05 ), the ejection-fraction (EF) improvement rate of the TXL group was 63%±7%, significantly higher than that before treatment (52% ± 6% ) and that of the conventional treatment group (59% ± 8% , both P 0.05 ) . Conclusion TXL capsule in addition to conventional therapy has a positive effect on the prognosis of AMI via reversing the ventricular remodeling, and improving cardiac function.

Objective To explore the clinical significance of detection of cytokeratin 19 (CK19) Mrna and carcinoembryonic antigen (CEA) Mrna expression in the diagnosis of micrometastasis in the peripheral blood of patients with breast cancer, and the relationship with other clinieopathological characteristics. Methods Peripheral blood samples were collected from 28 normal female healthy volunteers, 20 patients with benign breast disease, and 108 patients with breast cancer (88 had undergoneoperation and 20 with metastasis). Real-time quantitative PCR was used to detect the Mrna expression of CK19 and CEA in the peripheral blood. Results Mrna expression was negative in the blood samples from the 28 normal volunteers for both CK19 and CEA. None of the 20 patients with benign breast disease was positive for CEA Mrna, but one was positive for CK19 Mrna (5%). Of the 108 patients with breast cancer, 26 (24.1%) were positive for CK19 Mrna, 23 (21.3%) were positive for CEA Mrna, and 15 ( 13.9% ) were positive for both CK19 Mrna and CEA Mrna. The positive rates of CK19 Mrna and/or CEA Mrna of the metastatic breast cancer patients were higher than those of the operable breast cancer patients. Statistically significant differences in tumor size, clinical stage, and expression levels of kI67, variant exon 6 containing isoforms of CD44 (CD44v6), and vascular endothelial growth factor(VEGF) were found between the operable breast cancer patients with micrometastasis in peripheral blood and the patients without micrometastasis ( all P 0.05). And there was no statistically significant difference between the twogroups in age, tumor location, pathological histological type, nodal metastasis, and expression levels of estrogen receptor ( ER), pregnant receptor ( PR ), CerbB2, and matrix metalloproteinase-9 ( MMP9 ) ( all P0.05). Multivariate analysis showed that tumor size, clinical stage, expressions of kI67, CD44v6, and VEGF were associated with mierometastasis in peripheral blood. Conclusion The combined detection of CK19 and CEA Mrna raises the detection rate of micrometastasis in the peripheral blood of breast cancer patients. Tumor size, clinical stage, expressions of kI67, CD44v6, and VEGF are effectivepredictors of micrometastasis in the peripheral blood of breast cancer patients.

Objective To explore the association between plasma fibrinogen (FIB) concentration and ten-year change in blood pressure in Chinese population aged 35 -64. Methods A prospective cohort comprising 2683 subjects was established in Beijing in 1992. Blood pressure (BP) and other traditional cardiovascular risk factors were assessed in 1992 and 2002 respectively, and plasma FIB concentration was measured in 1992. The association of plasma FIB with ten-year change in blood pressure was analyzed. Results (1) The median concentration of FIB among this population was 3. 8 g/L (3.2 -4. 3 g/L), and the percentage of the people with abnormal FIB concentration ( FIB4. 0 g/L) was 33.4% in 1992. The FIB concentration of the females was higher than that of the males (P0. 01 ) and the FIB concentration of the hypertensive subjects was significantly higher than that of the non-hypertensive subjects ( P 0. 05 ), however, there was no significant difference in the abnormal FIB rate among different age groups. (2) Compared with the BP levels in 1992, the systolic BP and diastolic BP of this population increased by 10. 0 mm Hg and 5.0 mm Hg respectively in 2002. The partial correlation coefficients of baseline FIB concentration with ten-year difference for systolic and diastolic BP were 0. 125 (P 0. 01 )and 0. 047 (P 0. 05) respectively, and the absolute value of 10-year increase of systolic pressure in the subjects with abnormal FIB was significantly higher than that in those with normal FIB ( P0. 01 ). (3) The BP grade 2002 was higher than the baseline grade in 1992 in 49. 6% of the study population. The BP grade increase rate of the subjects with abnormal FIB was 55.3%, significantly higher than that of the subjects with normal FIB (46. 8%, P0. 05). (4) In the population without baseline hypertension the risk of BP grade increase within 10 years in those with abnormal FIB was 1.46 times the risk in those with normal FIB, the multivariable OR (95% CI) was 1. 457 ( 1. 201 - 1. 768 ) for those with normal BP and 2. 082 ( 1. 422 - 3. 048) for those with hypertension. Conclusion Plasma FIB concentration is associated with the BP change. Improvement of high coagulation and high adhesion help control BP. Especially in people with hypertension.

Objective To evaluate the efficacy of sequential administration of gefitinib and docetaxel in the second-line therapy for advanced non-small cell lung cancer (NSCLC). Methods Eighty- two patients with advanced NSCLC who had received both gefitinib and docetaxel treatment were divided into 2 groups: Group A ( n = 17) that were treated with gefitinib first and then crossed over to docetaxel treatment when progressive disease (PD) occurred as second-line treatment, and Group B (n = 65) that were treated with docetaxel first, and then crossed over to gefitinib treatment when PD occurred. Results The response rate of gefitinib in phase Ⅰ ( duration before crossover) was 27.7%, not significantly different from that in phase Ⅱ (duration after crossover) (29.4%, P 0. 05). The response rate of docetaxel in phase Ⅰ was 13.8%, not significantly different from that in phase Ⅱ (5. 9%, P 0. 05 ). Gefitinib showed an efficacy superior to docetaxel after adjusting the sequence of these two agents (28.0% vs 12. 2%, x2 = 5.46, P = 0. 02). The time to progression (TTP) of gefitanib was 6. 0 months, signifieandy longer than that of docetaxol (4. 0 months, P =0. 00). Though no statistically significant survival difference was seen between these two groups, stratified analysis showed that the median survival time of the patients with the Eastern Cooperative Oncology Group (ECOG) = 2 in Group A was 13.0 months, significandy longer than that in Group B (6. 0 months, P = 0. 01 ). The adverse events (Aes), including skin rash and diarrhea were all generally tolerable. The incidence of Aes was similar in these two groups. Conclusion Although no impact was found in the efficacy and survival between these two different sequential administration of gefitinib and docetaxel for patients with advanced NSCLC, but the patients with poor performance status may get longer survival if they receive treatment of gefitinib first crossed-over to docetaxel.

Objective To analyze the effect of additional chromosome abnormalities on the prognosis and the clinical manifestations of acute promyelocytic leukemia (APL) and the reaction of the patients with additional chromosomes to the treatment of combination of red arsenic sulfide, all trans-retinoic acid (ATRA) and anthracyclin. Methods The clinical data of 158 patients with newly diagnosed APL who were treated with combination of red arsenic sulfide, ATRA, and anthracyclin were analyzed retrospectively. Results The frequency of additional chromosome abnormalities in the APL patients was 18.4%, and trisome 8 and i17q- were the most to be seen. The disseminated intravascular coagulation rate of the patients with additional chromosome abnormality was 62. 1%, significantly higher than that of the patients without additional chromosome abnormality ( 35.6%, P 0. 05 ). The complete remission rate of the patients with additional chrosome abnormality was 75. 9%, not significantly lower than that of those without additional chrosome abnormality (90. 7% ) , and the relapse rate and incidence rate of central nervous system leukemiawere 13.8% and 17. 2%, both higher, but not significantly, than those of the patients without additional chromosome abnormality ( 6. 2% and 6. 2% respectively ) ( all P0. 05 ). There was no significant difference in survival rate between these 2 groups (P = 0. 160 ). Conclusion Additional chromosome abnormality does not significantly influence the prognosis of APL treated with combination of red arsenic sulfide, ATRA, and anthracyclin.

Objective To investigate the impact of glucokinase-associated dual-specificity phosphatase 12 gene (DUSP12) single nucleotide polymorphism (SNP) on type 2 diabetes mellitus in Chinese. Methods The genotypes of -6735T→C of DUSP12 were determined by PCR-RFLP in 577 Chinese in Shanghai, 359 with normal glucose tolerance (NGT) and 218 being newly diagnosed DM patients without taking any drug. Oral glucose tolerance test was conducted. Height, weight, glucose and insulin concentrations, serum lipid profiles, and fat distribution parameters were determined. Results The genotype frequency distributions of -6735T→C variant in DUSP12 gene of the DM group and NGT group were not significantly different ( all P 0.05 ). The fasting plasma glucose concentration of the NGT subjects with C allele was 5.00 ( 4.69 - 5.28 ) mmol/L, significantly higher than that of the subjects with TT genotype [ 4. 90(4.50- 5.26 )mmol/L, P = 0. 035 ] . The serum HDL-c concentration of the NGT subjects with Callele was ( 1.25 ± 0.30 ) mmol/L, significantly lower than that of those with TT genotype [ ( 1.34 ± 0.30) mmol/L, P = 0. 010]. These two results still showed significant statistical differences after adjusted with sex, age, and BMI (P =0. 035). Conclusion -6735T→C variant in DUSP12 doesn't play a major role in diabetes, but it may have some effects on glucose and lipid metabolism.

Objective To observe the pharmacokinetics of adriamycin-adsorbing nanometric activated carbon in intralymphatic chemotherapy. Methods Two ml of suspension of activated carbon with the diameter of 21 nm was mixed with adriamycin 5 mg. Eighteen dogs were randomly divided into 6 equal groups. The above mentioned mixture was injected subserosally to the anterior wall of gastric antrum of the dogs. Thirty minutes, 1 h, 2 h, 1 day, and 3 days after the injection the gastruepiploic lymph nodes of the Groups 1 -5 were obtained. And Group 6 underwent extraction of venous blood samples 5, 15, 30, 60, 120, and 240 minutes after the injection and extraction of thoracic duct fluid 5, 15, 30, 60, 120,240, and 360 minutes after the injection. The adriamycin concentrations at different time points were determined by mass spectrometer. The lymphatic vessels and nodes at the gastric wall were observed by the naked eyes. Results Black tiny lymphatic vessels and lymph nodes were visualized around the injection areas immediately after the injection. Adriamycin content could be detected 30 min after the injection and lasted for 72 h at high levels with the peak content of (84. 6 ± 2.0) μg per gram tissue at 60 min in the paralymph node of gastroepiploic artery. The adriamycin concentration in the lymph fluid of thoracic duct reached the top level of 162. 5 ng/ml 30 min after the injection, and then decreased slowly. Adriamycin could be still detected in lymph fluid 6 h after injection. No trace of adriamycin was found in the blood at any time points. Conclusion The content of adriamycin can keep high and last long in the drainage of lymph node and lymph fluid in the treatment of intralymphatie chemotherapy using adriamycin-adsorbing nanometric activated carbon.

Objective To investigate the effect of DNA methyhransferases inhibitor 5-aza-2'deoxycytidine (5-Aza-CdR) on the histone H3-lysine 9 methylation status and gene expression of RUNX3 in human bladder tumor cells. Methods Human bladder tumor cells of the line EJ were cultured and treated with 5-Aza-CdR for 24 h. MTT test was used to observe the proliferation and growth of the EJ cells. Other EJ cells were cultured and treated with 5-Aza-CdR and then chromatin immunoprecipitation assay was used to analyze the histone H3-lysine 9 methylation status of RUNX3 promoter and the second exon. The expression of RUNX3 was measured by RT-PCR. Results The survival rate of the EJ cells treated with 5-Aza-CdR of the concentrations of 0. 1, 0.5, 1.0, 2.0, 5.0, and 10.0 μmol/L were 98. 1%, 95.3%, 75.9%, 52.3%, 16. 2%, and 7.7% respectively. And the survival rates of the EJ cells treated with 5-Aza-CdR for 12, 24, 36, 48, 72, and 96 hours were 89.4%, 85.2%, 78.6%, 37.1%, 8.9%, and 7.1% respectively. The survival rates of the 1.0, 2.0, 5.0, and 10. 0 μmol/L group were significantly lower than that of the control group ( all P 0. 05 ). Before the intervention, the amplified bands of the histone H3- lysine 9 methylation status of RUNX3 gene promoter and the second exon zone were obvious, but both disappeared after the treatment with 2. 0 and 5.0 μmol/L 5-Aza-CdR. Before the intervention, RUNX3 gene was not expressed, and was expressed after treatment with 2.0 μmol/L 5-Aza-CdR. Conclusion 5-Aza- CdR not only obviously inhibits the proliferation of human bladder cancer cells but also reactivates RUNX3 gene through demethylation of histone H3- lysine9 at RUNX3 promoter and the second exon. H3-lysine 9 trimethylation may be one of the most important reasons for gene inactivation of the RUNX3 gene.

：Objective To develop asimple, precise, and specific method for measurement of tacrolimus in whole blood. MethodsTacrolimus was extracted from the blood samples of 40 patients treated with tacrolimus byliquid-liquid extraction. Then high performance liquid chromatography-mass spectrometry(HPLC/MS) was used, with ascomycin as internal marker, to isolate the tacrolimus andmeasure the concentration thereof. The standard curve was drawn. The linearity ofquantitative measurement was determined. Detection limits test, CV test, and recovery testwere performed. ELISA was used simultaneously. The results of these 2 methods werecompared. Results A good standard curve was drawn based on the results of HPLC/MS assay(y=0. 2464x +0. 0082,R2 =0. 9996). The detected data were highly related to the detectedconcentrations. The linearity range was 0. 100 -40. 000 ng/ml( y = 1. 0294x -0. 035, R2=0. 9998). The detection limit of the assay was 0. 100 ng/ml. The CV values by this assaywere basically 5%. The recovery rate ranged 95.67% -98. 30% for tacrolimus over the range0. 300 - 16. 016 ng/ml. There was a linear correlation (y = 1. 0172x + 0. 3742, R2 = 0.9630) between the assay results by HPLC/MS to ELISA in blood. The measurement value ofELISA was ( 19 ± 9), significantly higher than that of HPLC/MS ( 18±9, P0. 01 ).Conclusion This newly developed method of HPLC/MS is simple, precise, and specific andwith lower cost, it can be used in the clinical practice and experimental study ontacrolimus.

Objective To explore the effects of systemic glucocorticoid treatment on tuberculous pleural effusion. Methods Ninety Wistar rats were intrapleurally injected with 0.03 mg of standard human Mycobacterium tuberculosis to establish models of tuberculous pleural effusions and then were randomly divided into 2 equal groups both without anti-tuberculosis treatment: glucocorticoids group (GG) undergoing intramuscular injection of 0. 3 mg triamcinolone acetonide in the right thigh 24 h after intrapleural injection, and control group (CG) received nothing as control. 8, 24, 32, and 48 hours, and 3, 5, 7, 10, and 15 days after intramuscular injection 5 rats from each group were killed. The thorax was opened, the amount of pleural effusion (PE) was recorded, and the pleural cavity, histopathology of pleura and lung parenchyma were examined. The white blood cell (WBC) count and differential leukocyte count, and levels of total protein (TP), glucose (GLU), and lactic dehydrogenase (LDH) in the PE were determined. Bioassays were used to detect the PE levels of soluble intercellular adhesion molecule-1 ( sICAM-1 ), transforming growth factor β1 ( TGF-β1 ), and interferon γ (IFN-γ). Results The PE volumes of GG 8 -48 h after the intramuscular injection were significantly lower than those of CG ( P 0. 05, P 0.01 ), and PE completely disappeared on day 3. The WBC in PE 24 -48 h after and the percentages of neutrophils 8 -48 h after the intramuscular injection of GG were all significant lower than those of CG (all P0. 01 ). The TP levels 32 and 48 h after the intramuscular injection of GG were both significantly higher than those of CG ( both P 0. 01 ). The LDH level of GG within 24 h after the intramuscular injection was significantly lower than that of CG (P 0. 01 ). Both the sICAM-1 and TGF-γ1 levels of GG were higher 8 h after the intramuscular injection, but lower 48 h after the intramuscular injection than those of CG ( both P 0. 01 ). The IFN-γ levels 8 -48 h after the intramuscular injection of GG were all higher than those of CC (all P 0.01 ). The IFN-γ//TGF-β1 ratios at different time points of GG were all higher than those of CG, and there were significant differences in those 8 - 48 h after the intramuscular injection between these 2 groups ( all P 0.01 ). Pathologically, the mean thickness of pleura in GG was significantly less than that in CG. Congestion and edema in subpleura and pulmonary interstitium were less in GG than in CG. Conclusion Early use of glucocorticoids helps reduce the inflammatory response in pleural cavity in tuberculous pleurisy accelerate the absorption of pleural effusion and decrease the thickness of pleura.

Objective To investigate the Dynamic effects of glucocorticoid (GC) on bone mineral density and microarchitecture time-related changes of trabecular bone in bone mineral density (BMD) and microarchitecture in glucoeorticoid -treated rats. Methods Fifty-two 3.5-month-old female SD rats were randomly divided into 3 groups. Ten rats were killed at the beginning of experiment with their right tibiae taken out as the baseline group; 22 rats underwent subcutaneous injection of methylprednisolone once daily (GC-treated group) , and the other 20 rats underwent subcutaneous injection of normal saline once daily as control group. One and 9 weeks after the beginning of experiment 11 and 10 rats from GCT Group and control group each were killed with their right tibiae taken out. High resolution micro-CT was used to identify the densimetric and microarchitectural properties of the trabecula in the proximal metaphysic of tibia. Results Compared with the control group the values of volumetric BMD ( vBMD ), tissue BMD ( tBMD ), bone volume fraction ( BVF ) , trabecular number ( Tb. N ) , degree of anisotropy ( DA ) , and trabecular connectivity (Conn. D) in the trabecular bone at different time-points, of the GCT group all decreased; and the values in the ninth week were the lowest (all P 0. 05). The values of trabecular thickness (Tb. Th), trabecular separation (Tb. Sp), and structure model index (SMI) at different time-points of the GCT group were higher than those of the control group. A time-related analysis within the GCT group showed there was a declination in BVF, Conn. D, Tb. N, and DA with administration time, but Tb. Th and Tb. Sp were increased significantly ( all P 0. 05 ). The mean values of Tb. Th in the first week and the ninth week of GCT Group were ( 0. 076 ± 0. 020 ) mm and ( 0. 086 ± 0. 026 ) mm respectively, both higher than the baseline value [ (0. 067 ± 0. 014) mm] and the values of the control group in the first and ninth weeks [ (0. 075 ± 0. 022) mm and (0. 072 ± 0. 009) mm respectively]. Conclusion Administration of GC time-dependently decreases the BMD and causes deterioration in microarchitecture of trabecular bone; and the remaining trabeculae seem thicken to increase their strength as compensation.

Case 1: A 53-year-old male, Uygur peasant, came to the stomatology department in August 2000. Because of the different language, our hospital translated: intermittent pain in the left mandibular posterior teeth for more than 10 hours. The pain was skipping, which could be relieved by taking cold water in the mouth.

The term clinical epidemiology appeared in the 1930s, formed as a discipline in the late 1970s and early 1980s under the joint efforts of David L. Sackett and other scholars, and continues to today.Clinical epidemiology was introduced in China in the early 1980s through the loan of the World Bank and the funding of Roche Foundation.