Volume 91  ·   Issue 06  ·  2011

Objective To evaluate the relationship between the clearance rate of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) in scintimammography and the efficacy of neoadjuvant chemotherapy (NCT) of patients with operable breast cancer.Methods Seventy-eight patients with breast cancer underwent 99mTc-MIBI scintimammography at pre-NCT.And static planar images were taken at 10 min and 180 min post-scintimammography.The clearance rate was calculated in each patient.And the efficacy of NCT was evaluated after 2 cycles.Results The clearance rates of patients with a poor or good efficacy of chemotherapy were 24.21% ± 6.38 % ( n = 14 ) and 14.13 % ± 5.98% ( n = 64 ) respectively.There was significant difference between two groups.And a significant correlation was observed between the efficacy of chemotherapy and the clearance rate of 99mTc-MIBI ( r = - 0.539,P ＜ 0.001 ) .Conclusion The scintimammography of 99mTc-MIBI may be employed to evaluate the efficacy of NCT.

Objective To investigate the relationship between janus kinase2/signal transducer and activator of transcription 3 (JAK2/STAT3 ) signaling pathway and angiogenesis in non-small cell lung cancer (NSCLC) and explore the effects on the mRNA expression of vascular endothelial growth factor (VEGF)and basic fibroblast growth factor (bFGF) by blocking JAK2/STAT3 signaling pathway.Methods Immunohistochemistry was used to determine the expression of P-JAK2,P-STAT3 and microvessel density (MVD) in 68 NSCLC tissues and 27 normal lung tissues.And the relationship with their clinical pathological features was analyzed.Human lung cancer A549 cells were treated with different concentrations of AG490.Cell proliferation was measured by MTF assay.Western blot was performed to detect the activation of JAK2/STAT3 signaling pathway.The mRNA expressions of VEGF and bFGF were determined by RT-PCR (reverse transcription-polymerase chain reaction).A549 cells were transfected with STAT3 siRNA.And the protein of STAT3,Phos-STAT3 (P-STAT3) and mRNA levels of VEGF and bFGF were detected.Results The activation of JAK2/STAT3 signaling pathway was closely related to MVD in NSCLC.AG490 and STAT3 siRNA could block the JAK2/STAT3 signaling pathway and down-regulated the mRNA expressions of VEGF and bFGF in lung cancer cells.Conclusion JAK2/STAT3 signaling pathway plays an important role in the angiogenesis of NSCLC.Blocking this pathway may inhibit the expression of angiogenic cytokines.JAK2/STAT3 signaling pathway may be a critical therapeutic target for the treatment of angiogenesis in NSCLC.

Objective Sildenafil has been shown to be effective in pulmonary arterial hypertension (PAH).However,the impact of sildenafil on PAH has been under-investigated in China.The aim of the present study was to evaluate the efficacy and safety of oral sildenafil in PAH patients in China.Methods In this prospective,open-label and multi-center study,90 patients were recruited from 14 centers to receive oral sildenafil (75 mg/d) for 12 weeks.They underwent a six-minute walk test (SMWT) and cardiac catheterization at the beginning and the end of 12 weeks.The primary endpoint was the changes in exercise capacity as assessed by SMWT.And the secondary endpoints included assessment of functional class,evaluation of cardiopulmonary hemodynamics and clinical deterioration (defined as death,transplantation and re-hospitalization for PAH).Drug safety and tolerability were also examined.Results There were 19 males and 71 females with an average age of 32.5±12.1 years old(range: 18-61 ).Their etiologies were idiopathic (n=15),related with congenital heart disease ( n = 60 ),or related with connective tissue disease (n=9) and chronic thromboembombolic pulmonary hypertension ( n = 6).Oral sildenafil significantly increased the SMWT distances [(342±93) m vs.(403±88) m,P＜0.001].There was also remarkable improvement in Borg dyspnea score ( 2.9 ± 2.6 vs.2.4 ± 2.0,P = 0.005 ).Furthermore,significant improvements in World Healthy Organization (WHO) functional class and cardiopulmonary hemodynamics were also found ( mean pulmonary artery pressure,P ＜ 0.001; cardiac index,P ＜ 0.001; pulmonary vascular resistance,P ＜ 0.001 ).Side effects were mild and consistent with other reports.Conclusion This study confirms and extends previous studies.Oral sildenafil is both safe and effective for the treatment of adult PAH patients in China.

Objective To analyze the treatment efficacy after a failed regimen of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in patients with advanced non-small cell lung carcinoma (NSCLC).Methods A retrospective analysis was conducted for 87 patients with advanced NSCLC at our hospital from January of 2005 to December of 2006.All subjects received chemotherapy after a failure of EGFR-TKI,there were 37 cases of male and the median age was 56 ± 11 ( range,31-76) years,50 cases of female,median age 56±13 (range,31-78) years; They received a 2-drug combination chemotherapy (n=61) and a monodrug chemotherapy (n = 26).The primary endpoint was overall survival (OS).And the secondary endpoints were objective response rate (ORR) and side effects.Results The OS was9.4±6.0(range,2-33) months and ORR 9.2%(8/87).The OS was 9.1±5.2 (range,2-31)months in combination chemotherapy group and 10.0±7.3(range,3-33) months in monodrug group; the ORRs were 11.5%(7/61) and 3.8%(1/26) respectively in two groups.There was no significant difference in OS and ORR between two groups ( P ＞0.05 ).The common side effects were myelosuppression and nausea/vomiting.The rate of myelosuppression was 87.4%(76/87) and that of 3/4 grade myelosuppression 33.3% (29/87).And the rate of nausea/vomiting was 86.2% (75/87) and that of 3/4 grade nausea/vomiting 10.3% (9/87).Other side effects were mild and well-tolerated.Conclusion If tolerated,chemotherapy after an EGFR-TKI failure may prolong the survival in advanced NSCLC patients.

Objective To explore the studies and application status of sentinel lymph node biopsy (SLNB) in breast cancer in China by statistically analyzing the relevant domestic literature.Methods The literatures published from January 1999 to December 2005 were searched in the databases of ChinaInfo,CBM and CNKI retrieval system with "breast tumor,SLN and SLNB" as the key words.A total of 88 manuscripts were selected with 2 new reports of SLNB.The successful rate,accuracy,false-negative rate and sensitivity of SLNB were analyzed by SPSS 10.0 statistical analysis software.Results Among a total of 6282 patients,the detection rate of SLNB was 90.82%(5705/6282) and the overall false-negative rate 9.69%(259/2671 ).The prediction sensitivity,specificity,false positive rate,accuracy,negative and positive predictive value of SLN for axillary lymph nodes status were 90.30%,99.64%,0.41%,86.52%,92.11% and 99.55% respectively.Conclusion SLNB can accurately predict the axillary lymph node metastasis.And its detection rate is correlated with patient age and tumor location.The detection rate and false-negative rate has nothing to do with the tracer injection site.A combined regimen has a higher detection rate and a low false negative rate.Affecting the whole breast,SLN is not correlated with a particular area of breast.The validation phase of SLNB in breast cancer is currently feasible in China.

Objective To investigate the long-term efficacy of ureteral reconstruction with tubularized peritoneal free grafts for the treatment of avulsion of ureteral mucosa in animal models.Methods The model of avulsion of ureteral mucosa was established in 12 adult dogs.Then they were divided into Group A (n = 6,length of avulsed mucosa at 4 cm) and Group B ( n = 6,length of avulsed mucosa at 6 cm).And the tubularized peritoneal free grafts and ureteral stents were implanted into the injured ureters.The curative effect was observed by intravenous urethrogram (IVU) and histological examination at Week 24 post-operation.Results Severe stenosis was observed by IVU in 1 dogs in Groups A and B respectively.In the remaining 10 dogs,IVU showed normal size and morphology of kidneys.There was no hydronephrosis.And no obvious stricture of ureteral part was observed for mucosa substitutes made of peritoneal free grafts.In all 10 dogs without stenosis of both groups,peritoneal membrane was replaced by integrated transitional epithelium.And there was no obvious stricture.Collagen fibers were arranged parallel to mucosal surface.Conclusion For avulsion of ureteral mucosa under 6 cm,reconstruction with tubularized peritoneal free grafts as mucosa substitutes is an effective method.And its long-term efficacy is satisfactory.

Objective To identify the presence of orexin receptor 1 (OXR1) in obese rat pancreas and clarify its effect and mechanism on body weight and metabolic index in obese rats.Methods The obese rat model was established a high-fat diet.And the serum levels of glucose,triglyeride and insulin were measured by Mini-Blood Glucose meter,biochemical enzymatic method and chemiluminescent immunoassay.The pancreatic expression of OX1R protein was bidentified by immunohistochemistry.After an intracerebroventricular infusion of orexin receptor 1 antisense oligodeoxynucleotide ( OX1R-PS-ODNs),the effect on OX1R protein was detected in rat pancreatic tissue with obesity.Results After feeding for 8 weeks,high-fat diet rats appear alimentary obesity body weight,serum glucose,insulin,triglyeride and cholesterol of high-diet rats were higher than those in the control group( P＜0.05 ).The expression of OX1R protein was located in the cytoplasm of pancreas Islet 3-cells.The expression of OX1R protein in obese rat pancreas decreased around 16% versus the normal group( P＜0.05 ).After the obese rats were treated by OX1R-PS-ODNs for 72 hours,the expression of OX1R protein in pancreas declined from 82 ±6 to 65 ±4,reduced about 21% compare with control group( P＜0.01 ).Conclusion The expression of OX1R protein is found in pancreas Islet β-cells.Hypothalamic orexin system can intervene the expression of OX1 R protein in rat pancreatic tissue with alimentary obesity.And it may participate in the occurrence of obesity and the metabolic regulation of serum glucose and insulin.

Objective To explore a new method of preventing Neisseria gonorrhea (N.gonorrhoeae) by simulating intercourse in mice and verify the effect of a long-acting antibacterial material in the gonococcal infection in mice.Methods (1) Simulated male-female gonococcal transmission: the estradio-treated BALB/c female mice were inoculated with N.gonorrhoeae WHO-L via a vaginal route.In treated group,the mice received the long-acting antibacterial material via vaginal route while deionized water was administered in the control group.At Days 2-10 post-inoculation,the average number of polymorphonuclear cells (PMNs) was monitored in stained smears of vaginal cells from test mice.And the vaginal fluid was cultured for N.gonorrhoeae at Days 2,4,5 post-inoculation.N.gonorrhoeae genital tract infection was determined to compare the difference between the two groups.(2) Simulated female-male gonococcal transmission: a treated or sham glass rod was used instead of male mice's penis to simulate intercourse in gonococcus-infected female mice.The vaginal fluid on top of glass top was eluted and cultured for N.gonorrhoeae and the difference of relevance ratios compared.Results ( 1 ) In the experiment of simulated male-female gonococcal transmission,At Days 4 and 5,the positive rates of culture for N.gonorrhoeae of the tested group were lower than those of the control group,and there was significant difference between both groups ( 10.0% vs 57.5%,7.5% vs 45.0%,both P ＜0.01 ).The percentage of PMNs in the treated group was significantly lower than that of the control group at Days 5-8 post-inoculation (all P＜0.05 ).(2) In the experiment of simulated female-male gonococcal transmission,the positive rates of culture for N.gonorrhoeae from the vaginal fluid on top of glass top were 8.3% and 0 at Days 1 and 2 in the tested group respectively.And they were significantly lower than those of the control group (72.7% and 45.5% respectively,both P＜0.01 ).Conclusion After topical application in murine vagina,the longacting antibacterial material forms a layer of physically antibacterial molecular film to prevent the occurrence of N.gonorrhoeae genital tract infection or colonization in mice.It may be used as a liquid condom for male mice.

Objective To study the effects of allergen and corticosteroid on T help 17 (Th17) and orphan nuclear receptor gammat (RORγt) in allergic-rhinitis mice.Methods Experimental allergic rhinitis (AR) was induced by the extract of dermatophagoides pteronyssinus (DP) including 2% ovalbumin (OVA)sensitization in 30 male mice with DP allergen group (n = 10),intranasal corticosteroid (budesonide,BUD) group (n = 10) or without treatment (model group,n = 10).And another 10 were included into the normal control group.The murine levels of Th17 were measured by flow cytometry (FCM).The expression of RORγt mRNA was measured by reverse transcription-polymerase chain reaction (RT-PCR) while that of RORγt protein in nasal mucosa detected by immunohistochemical staining.Results The expression of RORγt in nasal mucosa of AR model was higher than that in the control group ( 25 ± 5 vs 48 ± 10,P ＜0.01 ).But its expression declined significantly after the administration of local corticosteroid (48 ± 10 vs 31 ±6,P ＜0.01 ).The levels of RORγt mRNA and Th17 in the AR model group were significantly higher than those in the control group ( 18.4% ± 1.3% vs 27.5% ± 1.6%,0.43 ± 0.04 vs 0.64 ± 0.05,both P ＜0.01 ).The levels of RORγt mRNA and Th17 in the spleen of AR mice were significantly reduced by allergen dosing (27.5% ± 1.6% vs 20.0% ±2.1%,0.64 ±0.05 vs 0.54 ±0.03,both P ＜0.01 ) but not by corticosteroid ( P ＞ 0.05).Conclusions Allergen may affect the systemic immunity to inhibit the RORγt expression and block the Th17 differentiation in AR model.Local steroid only produces a marked effect through a down-regulated RORγt expression in nasal mucosa.

Objective To investigate the relationship between the resistance of methotrexate (MTX) enantiomer and the gene expression levels of folylpolyglutamate synthetase (FPGS).Methods The cell lines of MTX enantiomer resistance from 15 -55 μmol/L were obtained when the A549 cell lines were exposed intermittently and progressively to an incremental dose of each MTX enantiomer.The resistant index of MTX resistance cell lines were detected by MTT.The gene expressions of FPGS in cytoplasm and mitochondria were detected by real-time quantitative polymerase chain reaction (PCR).Results The resistance indice of D-( - )-MTX resistant cell lines were higher than those of L-( + )-MTX resistant cells (32.7±9.3 vs 11.5 ±2.9,P ＜0.05).The resistant indice of L-( + )-MTX /A549 were from 5 to 15,which mean the middle resistance.The resistant indice of D-( - )-MTX/A549 were more than 15,which mean the severe resistance.The expression of mFPGS had difference between resistant cell lines of L-( + )and D-( - )-MTX except at 15 μmol/L MTX (at 25 μmol/L,1.3 ±0.7 vs.2.3 ±0.9;at 35 μmol/L,1.1 ±0.9 vs.2.6±0.3;at 45 μmol/L,1.0±1.0 vs.1.4±0.8;at 55 μmol/L,0.2±0.1 vs.1.0±0.2;all P＜0.05).The expressions of cFPGS had no difference between resistant cell lines of L-( + ) and D-( - )-MTX at 15 μmol/L MTX,while at 25 -55 μmol/L,the cFPGS levels and resistance indice of D-( - )-MTX/A549 resistant cell lines showed a highly negative correlation ( r = - 0.95,P＜0.05 ).Conclusion There may be a different mechanism between the first time treatment with 15 μmol/L dosage and the continual treatment with more than 25 μmol/L dosage in A549 cell lines.There had higher resistant index in D-( - )-MTX/A549 cell line than in L-( + )-MTX/A549 cell line.The results indicated that the difference in chirality should be considered in clinical treatment with MTX.

Objective To explore the effects of sphingosine kinase 1 ( SphK1 ) on mucin (MUC)5AC overexpression under the induction of tumor necrosis factor-α(TNF-α).Methods The HBE16 airway epithelial cells were cultured,pretreated with SphK1-specific inhibitor DMS or transfected with SphK1 siRNA.Then each group was stimulated by a certain concentration of TNF-α.The relative contents of SphK1,COX-2,p-P38,p-ERK and IκBα were detected by Western blot while the levels of MUC5AC,PGE2 and cAMP analyzed by enzyme linked immunoassay.The transcription activities of cAMP-responseelement-binding protein and nuclear factor κB (NF-κB) were detected by luciferase reporter gene detection systen.The mRNA expressions of SphK1 and MUC5AC were detected by RT-PCR (reverse transcription-polymerase chain reaction ) .And the intracellular MUC5AC protein was detected by immunofluorescence.Results The levels of protein and mRNA expression of SphK1 and MUCSAC were obviously elevated [( 0.69 ± 0.12,0.86 ± 0.07 ),( 0.60 ± 0.09,0.79 ± 0.05 )] .They were all significantly higher than those in the control group ( 0.26 ± 0.03,0.33 ± 0.04,0.18 ± 0.06,0.22 ±0.10).There was an elevation of COX-2,PGE2,cAMP,p-P38,p-ERK,CREB and NF-κB activity (all P ＜0.01 );the production of IκBα protein was lower than that in the control group ( P= 0.003 ).DMS decreased the levels of MUC5AC mRNA expression (0.37±0.06) and protein production (0.27 ±0.04),lowered the production of COX-2,PGE2,cAMP,p-P38 and p-ERK,inhibited the activity of CREB and NF-κB and increased the IκBα production ( all P ＜0.01 ).Transfection of SphK1 siRNA showed the similar effects as DMS ( all P＜0.01 ).Conclusion SphK1 plays an important role in regulating the MUC5AC expression under the induction of TNF-α.And the activation of critical signal factors in that process is dependent on SphK1.

Objective To explore the role of cortactin in endocytosis of colon cancer cells and clarify the significance of its over-expression in colon cancer tissues.Methods Immunohistochemistry and Western blot were employed to detect the expression of cortactin in benign and malignant tissues and cells.Cell endocytosis was examined in cancer cells after siRNA treatment and DNA transfection with plasmid encoding cortactin wild type and domain deletion mutants.Results Cortactin was over-expressed in colon cancer tissues than in adjacent normal tissues.The expression rate was 77.5% in cancer tissues and 47.5% in normal tissues ( P ＜ 0.05 ).The value of transferrin uptake was 0.61 ± 0.02 in siRNA treated cancer cells and 1.01 ± 0.16 in the control cells (P ＜ 0.05).Intact molecule and sufficient level of cortactin was required for an optimal endocytosis of cancer cells.Cortactin was involved in coated-vesicle transportation in cells.Conclusion Endocytosis in colon cancer cells is dependent on an intact expression of CTTN.An over-expression of cortactin facilitates the signaling in invasion and metastasis related to endocytosis.

Objective To investigate the epidemiological characteristics of subclinical target organ damage (TOD) among urban adult residents with hypertension in Tianjin and evaluate its relationships with circulating renin-angiotensin-aldosterone system (RAAS). Methods An epidemiological survey was conducted on urban adult residents in Tianjin. The participants with uncomplicated hypertension were followed up to examine for target organ involvement, including left ventricular hypertrophy ( LVH), carotid plaque or intima-media thickening ( IMT),microalbuminuria (MAU) and estimated glomerular filtration rate (eGFR). Multivariate logistic regression was used to evaluate the relations between subclinical TOD and RAAS. Results A total of 1547 subjects with uncomplicated hypertension underwent further examinations for target organ involvement. The prevalence rates of LVH, carotid plaque, carotid IMT, MAU and eGFR ＜60 ml · min-1 · (1.73 m2)-1 were 37.7%, 38.2%, 35.4%, 33.7% and 4.4%, respectively. The prevalence rates were categorized according to the absence or presence of one marker, two or three markers of TOD at 20.5%, 34.7%, 33.7% and 11.1% respectively. According to the logistic regression analysisadjusting for age, gender, current smoking, current drinking, previous antihypertensive treatment, body mass index, mean systolic blood pressure, mean diastolic blood pressure, duration of hypertension and other risk factors, plasma renin activity ( OR 0.870, 95 % CI 0.791 -0.958, P = 0. 005 ) and plasma angiotensin Ⅱ (OR 1.005, 95% CI 1.001 -1.009, P =0.021 ) levels were independently associated with LVH,serum aldosterone level was independently associated with carotid IMT or plaque ( OR 1. 025, 95% CI 1. 000- 1. 050, P = 0. 048 ) and MAU ( OR 1. 049, 95% CI 1. 024 - 1. 074, P ＜ 0. 001 ). Conclusion Subclinical TOD is fairly common among urban adult residents with hypertension in Tianjin. And RAAS plays an important role in the pathogenesis of subclinical TOD.

With age,even in the absence of other diseases,a sedentary lifestyle can decrease left ventricular compliance,and decrease diastolic function.This is the matrix that causes diastolic heart failure.Recent studies have shown that the elderly people who adopt a sedentary lifestyle,especially women, have almost the same degree of ventricular stiffness as those with diastolic heart failure.

A 54-year-old male was hospitalized for the second time in the Department of Endocrinology, General Hospital of Tianjin Medical University on March 16, 2010, mainly due to fatigue, palpitation, hand shaking accompanied by weight loss for 10 months, unsteady walking for 20 days, confusion, intellectual retardation for 4 days, and paroxysmal transient reversible loss of consciousness for 2 days. The patient complained of anemia 17 years ago and was cured by oral medication. For the past 2 months, I was treated with oral vitamin B12 and folic acid due to fatigue. 15 years ago, I suffered from hyperthyroidism (referred to as hyperthyroidism for short), and after 1 1/2 years of oral methimazole treatment, I improved and stopped the drug. I denied the history of heart, brain, kidney, hepatitis and drinking history, and had no partial eclipse.

A 64-year-old woman was admitted to the hospital for "episodic dyspnea for 17 months and recurrent for 13 h". 17 months ago, she had sudden dyspnea, accompanied by malignant vomiting, sweating, no chest pain, and immediately lost consciousness. She was diagnosed with "acute anterior myocardial infarction, cardiogenic shock" in the local hospital. She was given tracheal intubation, ventilator-assisted ventilation, thrombolysis, antiplatelet, anticoagulation, and pressurization treatment. After 1 d, the patient's consciousness gradually recovered, and after 20 d, she was discharged from the hospital in a stable condition. She came to our hospital for coronary angiography. At that time, the physical examination of admission showed that blood pressure was 156/84 mm Hg (1 mm Hg =0.133kPa), and cardiopulmonary auscultation was negative.

The prevalence of diabetes is increasing rapidly worldwide. Although there are many kinds of therapeutic drugs, the achievement rate of diabetes treatment is only about 40% [1]. Type 2 diabetes is a chronic progressive disease, and with the deterioration of pancreatic islet β cell function, it is bound to be more and more difficult for patients to control blood glucose [2]. 　　

Testicular torsion, also known as spermatic cord torsion, is a state in which the testis twist along the longitudinal axis of spermatin, which causes the blood supply to the testis to decrease or interrupt, resulting in ischemia and necrosis of the testis tissue. It has been found that testicular torsion reduction is a typical ischemia-reperfusion injury (IRI) process, which can cause increased apoptosis of testicular germ cells, leading to different degrees of testicular atrophy and low spermatogenic function.

A 38-year-old male was seen in the Department of Endocrinology of Peking Union Medical College Hospital in April 2009 due to polydipsia, polyphagia and polyuria for more than 10 years and weight loss for half a year.The patient had symptoms of polydipsia, polyphagia and polyuria without obvious trigger since 1996, and his blood glucose was all>20 mmol/L at random for three times. He was treated with oral hypoglycemic drugs, insulin and traditional Chinese medicine, but the control was unstable.