Role of PNPT1 in cardiomyocyte apoptosis induced by oxygen-glucose deprivation / 南方医科大学学报

OBJECTIVE@#To explore the effect of inhibiting polyribonucleotide nucleotidyl-transferase 1 (PNPT1) on oxygen-glucose deprivation (OGD)-induced apoptosis of mouse atrial myocytes.@*METHODS@#Cultured mouse atrial myocytes (HL-1 cells) with or without OGD were transfected with PNPT1-siRNA or a negative control siRNA (NC-siRNA group), and the cell survival rate was detected using CCK-8 assay. The expression levels of ACTB and TUBA mRNA were detected with qPCR, and the protein expression of PNPT1 was detected with Western blotting. The apoptosis rate of the treated cells was determined with flow cytometry, the mitochondrial membrane potential was detected using JC-1 kit, and the mitochondrial morphology was observed using transmission electron microscope.@*RESULTS@#With the extension of OGD time, the protein expression levels of PNPT1 increased progressively in the cytoplasm of HL-1 cells (P < 0.05). Transfection with PNPT1-siRNA significantly reduced PNPT1 expression in HL-1 cells (P < 0.05). Exposure to OGD significantly enhanced degradation of ACTB and TUBA mRNA (P < 0.05) and markedly increased the apoptosis rate of HL-1 cells (P < 0.05), and these changes were significantly inhibited by transfection with PNPT1-siRNA (P < 0.05), which obviously increased mitochondrial membrane potential and improved mitochondrial morphology of HL-1 cells exposed to OGD.@*CONCLUSION@#Inhibition of PNPT1 improves mitochondrial damage and reduces degradation of apoptotic-associated mRNAs to alleviate OGD-induced apoptosis of mouse atrial myocyte.

Treatment of refractory Her-2 positive metastatic young breast cancer with pyrrolidine combined with capecitabine: a case report / 中国综合临床

In order to explore the treatment of Her-2 positive breast cancer patients who failed in multi-line treatments, we retrospectively analyzed the clinical data of a patient with refractory Her-2 positive breast cancer.The patient was initially diagnosed as Her-2 positive advanced breast cancer.After six line treatment in the outer hospital, the patient′s condition was basically in a progressive state.The breast tumor was broken and purulent, the lung metastasis increased, and the patient′s quality of life was poor.The patient was admitted to Department of Breast Surgery of Affiliated Suqian Hospital of Xuzhou Medical University, after MDT discussion, we gave pyrrolotinib combined with capecitabine treatment, the chest wound healed gradually, the lung metastasis gradually reduced, and the quality of life was better.A retrospective analysis of this case showed that pyrrolidine combined with capecitabine may bring hope to Her-2 positive breast cancer patients who failed to receive multi-line therapies, especially those who failed to target therapy.

TP and FAC effect on patients with primary tumor molecular typing luminal A, axillary lymph node metastasis three negative breast cancer / 中国综合临床

Objective To explore the application of paclitaxel or docetaxel combined with cisplatin (TP) with cyclophosphamide,pirirubicin and fluorouracil (FAC) in the primary tumor molecular typing Luminal A,axillary lymph node metastasis three negative breast cancer. Methods From January 2012 to January 2014, the clinical data of forty-nine patients with were selected. All patients were divided into two groups by balance randomization method, TP group and FAC group. Twenty-five patients were treated with TP regimen and 24 patients were treated with FAC regimen. The clinical efficacy was evaluated after six cycles of chemotherapy. Chemotherapy effects,adverse reactions and survival rates of two groups were compared. Results All patients were given intravenous chemotherapy according to the plan and were evaluated for clinical efficacy. The response rate (RR) was 64. 0％ in TP group,including 4 cases of complete remission (CR),12 cases of partial remission (PR),7 cases of stable disease(SD) and 2 cases of progressive disease(PD). The adverse reactions were gastrointestinal reactions and granulocytopenia. The median progression-free survival ( PFS) and overall survival ( OS) were respectively 12. 4 months and 34. 1 months. In FAC group,the response rate ( RR) was 33. 3％,including 2 cases of CR,6 cases of PR,11 cases of SD and 5 cases of PD. The adverse reactions were gastrointestinal reactions,granulocytopenia and premature atrial contraction. The median PFS and OS were 7. 2 months and 20. 7 months respectively. The effective rate of TP group was higher than that of FAC group (χ2=4. 608,P=0. 032),and the progression-free survival time and total survival time were longer than those of FAC group (χ2 =8. 317, 8. 563, P=0. 004, 0. 003 ) . Conclusion Compared to FAC regimen, TP regimen could improve the survival rate of patients better with breast cancer of Primary tumor Luminal A and Axillary Lymph Node Metastasis Triple negative type, and adverse reactions were tolerated, it may be an optimized chemotherapy.

Pathological features and survival of triple positive breast cancer in 271 cases / 中国现代普通外科进展

Objective:To explore pathological features and survival of triple positive breast cancer (TPBC).Methods:The clinical data of 271 cases of triple positive breast cancer from January 2010 to January 2017 in Suqian area were collected,compared with 283 cases of Luminal B I (HER2 negative).The clinical pathological features and survival were analyzed.Results:Among 271 cases of triple positive breast cancer,there were 89 cases (32.84％) of distant recurrence and metastasis in 2 years,and 137 cases (50.55％) of distant recurrence in 5 years.Among 283 cases of Luminal B I,there were 32 cases (11.31 ％) of distant recurrence and metastasis in 2 years.and 52 cases (18.37％) of distant recurrence in 5 years.There were significantly differences(P＜0.05).1 year Disease-free survival (DFS)and Overall survival (OS) of all patients were 100％,Among 271 cases of triple positive breast cancer,2-year DFS and OS were 64.94 ％,85.24％ respectively.3-year DFS and OS were 54.98 ％,69.74％ respectively,5-year DFS and OS were 43.54％,47.23％ respectively.Among 283 cases of Luminal B I,2-year DFS and OS were 86.22 ％,95.76％ respectively.3-year DFS and OS were 81.98 ％,80.92％ respectively,5-year DFS and OS were 76.33％,67.49％ respectively.There were significantly differences(P＜0.05).Conclusion:TPBC has the characteristics of poor biological behavior,large mass,pathological grade of grade Ⅲ,vascular or nerve infiltration,axillary lymph node metastasis,high proliferation index and high tumor load,and early distant recurrence,low DFS and OS.We Should choose individualized,targeted treatment programs,based on patient's hormone receptor and Ki67 expression,so as to benefit patients of TPBC.

Clinical study of gefitinib plus capecitabine in treatment of recurrent and metastatic triple negative breast cancer / 中华内分泌外科杂志

Objective To evaluate the efficacy and safety of gefitinib plus capecitabine in treatment of recurrent and metastatic triple negative breast cancer.Methods From Jan.2011 to Jun.,41 patients who have recurrent and metastatic triple negative breast cancer after treated by adjuvant chemotherapy were enrolled in this study They were divided into two groups according to their wishes.The 24 cases in the experimental group were treated with gefitinib plus capecitabine.The 17 cases in the control group were treated with capecitabine.The two groups were followed up for 12 months.They were treated until the disease progression or the toxicity could not be tolerated.Results The objective response rate (ORR) in the experimental group and the control group was 70.83％(17/24) vs 35.29％(6/17).The disease control rate (DCR) in the two groups was 91.67％ (22/24) vs 64.71％ (11/17).The difference between the two groups was statistically significant (P＜0.05).The incidence rate of adverse drug reactions in the two groups was similar (P＞0.05),and the reactions were tolerable.Conclusion Gefitinib plus capecitabine is an effective and safe treatment for recurrent and metastatic triple negative breast cancer with tolerable adverse reactions,and some patients were able to survive for more than 12 months.

Crystal structures, absolute configurations and molecular docking studies of naftopidil enantiomers as-adrenoceptor antagonists

Chiral drug naftopidil (NAF), a specific-adrenoceptor (AR) antagonist for the treatment of benign prostatic hyperplasia, was used in racemic form for several decades. Our recent work declared that NAF enantiomers showed the same antagonistic effects on the-AR, but the binding mechanism of these two stereochemical NAF isomers to thereceptor remained unclear. Herein, we reported the crystallographic structures of optically pure NAF stereoisomers for the first time and unambiguously determined their absolute configurations. The crystal data ofandenantiomers matched satisfactorily the pharmacophore model for-selective antagonists. Based on the constructedhomology model, molecular docking studies shed light on the molecular mechanism of NAF enantiomers binding to-AR. The results indicated that NAF enantiomers exhibited the very similar binding poses and occupied the same binding pocket.

Visual quality after femtosecond laser-assisted deep anterior lamellar keratoplasty with big-bubble method for the treatment of keratoconus / 眼科新进展

Objective To observe the visual outcomes of big-bubble deep anterior lamellar keratoplasty (DALK) for the treatment of keratoconus using a femtosecond laser.Methods A total of 30 patients (50 affected eyes) with keratoconus were enrolled in the study by the self control observation method.All the patients were treated with femtosecond laser assisted DALK by large bubble method,and the curative effect was observed.Results All the 30 patients underwent the surgery successfully.In the early time after the surgery,the corneal grafts were transparent,the corneal physiological thickness was restored,and the grafts fitted the implant bed elastic layer well.The uncorrected visual acuity and the best corrected visual acuity on day 7,1 month,6 months and 1 year after surgery were higher than those before surgery (all P ＜ 0.05),but there was no significant difference between above time points (all P ＞ 0.05).The corneal curvature and corneal astigmatism were significantly decreased after surgery,the thickness of the thinnest cornea was significantly increased after surgery (all P ＜0.05),but there was no significant difference between the different time points after surgery (all P ＞ 0.05).The endothelial cell density before surgery and 1 year after surgery was (2989.34 ±294.52) · mm-2 and (2821.19 ±325.51) · mm-2,while loss rate of endothelial cell was (5.62 ± 0.56)％,but there was no significant difference between different time points after surgery (all P ＞ 0.05).There were no complications during the surgery,but wound dehiscence occurred in 1 eye,loose suture in 1 eye,and stromal rejection in 1 eye,and there was no other complication after surgery.Conclusion It is safe and effective of femtosecond-laser assisted DALK by a big-bubble method to treat keratoconus,and it is a good choice for patients with advanced keratoconus.

Three-dimensional DSA in displaying origin of uterine artery / 中国介入影像与治疗学

Objective To explore the value of three-dimensional DSA (3D-DSA) in displaying the location of the origin of uterine artery.Methods A total of 90 female patients underwent uterine artery (UA) embolization were enrolled.The bilateral internal iliac artery catheterization were performed by 3D-DSA,then the images were reconstructed in every 5 degree interval to choose the optimum range of viewing angle.The origination and the degree of the origin artery and UA were calculated.The distance between the origin of UA and superior glutea artery which was identified as the locating point was measured.Results Bilateral and contralateral oblique position of ＞30°-60°were the optimal projection positions of UA.Totally 64.44％ (116/180) of UA originated from the anterior trunk of internal iliac artery,18.33％ (33/180) originated from the inferior gluteal trunk,9.44 ％ (17 / 180) originated from the internal pundenal artery,5.56 ％ (10 / 180) originated from internal iliac artery,and 2.22％ (4/180) originated from the superior gluteal artery;10.56％ (19/180) of the angle of the origin artery and UA were 0-30°,38.89％ (70/180) were ＞30°-60°,41.11％ (74/180) were ＞60°-90°,4.44％ (8/180) were＞90°-120°,2.78％ (5/180) were＞120°-150°,2.22％ (4/180) were＞150°-180°.Distance between the origin of UA and superior gluteal artery was 3.04-18.31 mm,average was (11.71±4.28)mm.Conclusion 3D-DSA can clearly display the origination,viewing angle and the distance away from superior gluteal artery.

Study on the expression of hormone receptor and human epidermal growth factor receptor 2 in breast cancer primary tumor and axillary lymph node metastasis / 中国综合临床

Objective To explore the expression of HR and Her?2 in breast cancer primary tumor and axillary lymph node metastasis. Methods Four hundred and twenty?eight female patients with unilateral breast cancer combined with axillary lymph node metastasis treated in the Affiliated Suqian Hospital of Xuzhou Medical University from January 2011 to January 2016 were selected in this study. Immunohistochemistry was used to detect the expression of ER,PR,Her?2 and Ki67 in primary tumor and axillary lymph node metastasis. Results The positive rates of ER expression were 75. 9% ( 325/428 ) and 70. 3% ( 301/428 ) respectively in primary tumor and axillary lymph node metastasis. The positive rates of PR expression were 61. 4% ( 263/428) and 56. 1% ( 240/428 ) respectively in primary tumor and axillary lymph node metastasis. The rates of Her?2 overexpression were 20. 1% ( 86/428) in primary tumor and the positive rate of Her?2 in axillary lymph node metastasis was 22. 7%( 97/428 ) . The positive rates of Ki67 expression were 45. 6%( 195/428 ) and 39. 7%(170/428) respectively in primary tumor and axillary lymph node metastasis. The expression of ER,PR,Her?2 and Ki67 in primary and axillary lymph node metastasis showed no statistical significance ( P>0. 05 ) . The molecular typing of primary tumor and axillary lymph node metastasis were not consistent in 31 patients ( 31/428,7. 24%) ,including 14 cases of primary tumor Luminal A,9 cases of Her?2 overexpression in axillary lymph node metastasis and 5 cases of triple negative breast cancer. Primary tumor Luminal B was detected in 10 cases, while 6 cases of Her?2 overexpression in axillary lymph node metastasis and 4 cases of triple negative breast cancer. Primary tumor Her?2 was overexpressed in 4 cases,while 1 case of Luminal A,3 cases of Luminal B in axillary lymph node metastasis. There were 3 cases of primary tumor triple negative breast cancer,while 2 cases of Luminal B in axillary lymph node metastasis and 1 case of Her?2 overexpression. Conclusion The expressions of ER, PR, Her?2 and Ki67 in primary tumor and axillary lymph node metastasis of some breast cancer were different. Immunohistochemistry for primary tumor and axillary lymph node metastasis of stage II?III breast cancer patients should be routinely carried out. Based on molecular typing of primary tumor and axillary lymph node metastasis,individualized treatment plan can be developed,so that patients will benefit from it.

Modified procedure and clinical value for preserving intercostobrachial nerve in breast cancer operation / 局解手术学杂志

Objective To study the method and clinical value of preservation of intercostobrachial nerve( ICBN) by fat dissolving meth-od during breast cancer operation. Methods The clinical data of 50 cases withⅠ~Ⅲa stage breast cancer from January 2013 to June 2013 were analyzed. Fifty patients were randomly divided into two groups,there were 26 patients in preservation group,whose ICBN were preserved by fat dissolving method during axillary lymph nodes dissection,and 24 patients in resection group,whose ICBN were not preserved by routine method during axillary lymph nodes dissection. Comparison of operation times,bleeding volume,the number of axillary lymph nodes dissection and upper arm sensory function of patients after operation between both groups was done. Results The mean time of operation was (102. 3 ± 15. 6) min in preservation group and(95. 6 ± 12. 4) min in resection group,while the number of axillary lymph nodes dissection was (19. 5 ± 8. 8 ) in preservation group and ( 19. 2 ± 9. 5 ) in resection group, with no significant difference between both groups (P>0. 05). Bleeding volume was (51. 2 ± 11. 5)mL in preservation group and (98. 5 ± 13. 4)mL in resection group,with significant differ-ences(P<0. 05). After postoperative one month,we observed upper arm sensory function of patients. It showed that 3 cases of sensory numb-ness or pain occurred in preservation group (11. 5%),20 cases of sensory abnormality occurred in resection group (83. 3%),mainly as sen-sory loss,numbness,pain or burning sensation,there was significant difference between both groups (P<0. 05). All patients were followed up half a year,patients with sensory abnormality in preservation group recovered,and recovery in resection group was not obvious,it still showed sensory abnormality in varying degrees. During the follow-up,no local recurrence or distant metastasis was found in both groups. Conclusion Preserving intercostobrachial nerve by fat dissolving method in breast cancer operation is based on conventional operation and made a few of improvements. It is simple and feasible. During the operation,we find that the axillary neurovascular is clearer,preservation of ICBN is easier. It does not affect the axillary lymph node dissection and operation time,while it can reduce incidence of postoperative sensory abnormality and improve the quality of life of patients,therefore it is worthy of clinical application.

Efficacy comparison of different stimulation therapies for periarthritis of shoulder / 中国针灸

<p><b>OBJECTIVE</b>To compare clinical efficacy differences among electroacupuncture (EA), transcutaneous electrical nerve stimulation (TENS) therapy and acupoint massage (AM) on periarthritis of shoulder.</p><p><b>METHODS</b>One hundred and twenty cases were randomly divided into an EA group, a TENS group and an AM group, 40 cases in each one. The selection of acupoints in the three groups were all the same, which were Jianqian (Extra), Xiabai (LU 4), Jianyu (LI 15), Binao (LI 14), Jianliao (TE 14), Naohui (TE 13), Xiaohai (SI 8) and Houxi (SI 3). EA was applied in the EA group with dense-disperse wave for 30 min, TENS therapy with dense-disperse wave for 30 min in the TENS group and AM combined with mobilization manipulation of Tuina on the shoulder in the AM group. All of the treatment was given once a day, six times a week and totally 4 weeks were required. The score of visual analogue scale (VAS) and improvement of shoulder joint activities in the three groups before and after the treatment were observed.</p><p><b>RESULTS</b>After the treatment, the VAS score and activities of shoulder joint were all improved in the three groups (all P < 0.001) and AM group had more obvious improvement than TENS group and EA group (all P < 0.05). The effective and curative rate was 61.50 (24/39) in the AM group, which was superior to 42.9% (15/35) in the EA group and 44.4% (16/36) in the TENS group (both P < 0.05). The effective and curative rate of shoulder joint activities in the AM group was 61.5% (24/39), which was superior to 48.6% (17/35) in the EA group and 44.4% (16/36) in the TENS group (both P < 0.05).</p><p><b>CONCLUSION</b>The acupoint massage has obvious clinical efficacy on periarthritis of shoulder, which could effectively relieve the pain and improve activities of shoulder joint, and it is superior to EA and TENS therapy.</p>

Effect of promoter polymorphism of organic cation transporter OCTN1/2 on the susceptibility to Crohns disease: a Meta-analysis / 中华流行病学杂志

Objective To investigate the associations between polymorphisms of organic cation transporter OCTN1/2 (organic cation transporter 1/2) and the susceptibility of Crohn' s disease (CD) through a meta-analysis.Methods Databases of PubMed,EMBASE,MedLine,and CNKI (Chinese),Wanfang (Chinese) were searched for published case control studies on the association between polymorphisms of OCTN1/2 gene and the susceptibility of CD which were published before September 2012.The meta-analysis was applied with Review Manager 4.2 software and Stata 10.0 software.Results Nineteen eligible studies,including 14 from Europeans,3 from Asians,1 from Oceania,and 1 from the US were included in the meta-analysis.In total,significant associations were found between OCTN1/2 polymorphisms and the susceptibility of CD for all genetic models.In subgroup analyses,significant associations were found in the European population for OCTN1/2.Associations were not significant in the non-European population for OCTN1 (TT vs.CT:OR=1.25,95％CI:0.75-1.98,P=0.34; TT vs.CC+CT:OR=l.48,95％CI:0.95-2.29,P=0.08) and for OCTN2 (CC vs.GC:OR=1.03,95％CI:0.68-1.56,P=0.89; CC vs.GG + GC:OR=1.23,95％CI:0.83-1.82,P=0.31).However,there were significant associations found between OCTN1/2(TT vs.CC,TT+CT vs.CC,CC vs.GG,CC + GC vs.GG) polymorphisms and the susceptibility of CD found in the nonEuropean population.Conclusion Results from this meta-analysis suggested that OCTN1/2 polymorphisms were associated with the susceptibility of CD in the European population.Associations between OCTN1/2 polymorphisms and the susceptibility of CD in the non-European population required searching for large samples to confirm the findings.

Influence of central obesity on clustering of other risk variables on metabolic syndrome among adults with normal body mass index / 中华流行病学杂志

Objective To study the influence of central obesity on clustering of other metabolic syndrome (MS) risk variables among adults with normal body mass index.Methods Through cluster multistage and random sampling methods,local people aged ＞35 years old with normal body mass index (BMI=18.5-24.9 kg/m2) in Lanxi country were selected.Overnight fasting blood specimens of these people were collected.Chi-square test,analysis of covariance,and logistic regression analyses were performed.Results (1) 1821 residents were surveyed including 844 male and 977 female subjects.The overall prevalence of MS was 8.68％ and the overall prevalence of central obesity was 15.87％.Both prevalence rates of the two diseases appeared to be lower in males than in females(MS:3.32％ vs.13.31％; center obesity:5.57％ vs.24.77％,all P＜0.001 ).(2) The overall positive rate of clustering on other MS risk variable was 36.02％,with 34.12％ in males and 37.67％ in females.Comparing the subjects who did not have central obesity,those subjects wth central obesity had higher positive rate in other MS risk variables.(3) Data from analysis of covariance showed that the level of waist circumference appeared an upward trend along with the count of other MS risk variables (all P＜0.001 ).(4) Data from multivariable logistic regression analysis showed that central obesity was a risk factor on clustering of other MS risk variables.Conclusion Control the level of waist circumference among normal body mass index was an effective method in preventing metabolic syndrome and cardiovascular disease in adults.

Benign prostate hyperplasia induced by urogenital sinus implantation in rats: a histomorphological study / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the histomorphological and immunochemical characteristics of benign prostate hyperplasia (BPH) induced by urogenital sinus (UGS) implantation in the rat model.</p><p><b>METHODS</b>We randomized 32 seven-week old male SD rats into a sham operation control and three (2-, 3- and 6-week) UGS model groups. We made the UGS model by implanting two urogenital sinuses from homogeneous male rat embryos into the host rats' right anterior lobe, and killed the model rats 2, 3 and 6 weeks later for measuring the wet weight, volume and micromorphological parameters of the right anterior lobe and detecting the factors expressed in the epithelium, stroma and smooth muscle by immunochemistry.</p><p><b>RESULTS</b>The model rats showed significant increases in the wet weight, volume and relevant indexes of the right anterior lobe (P < 0.05), as well as in the proportion of stromal area and relative stromal volume (P < 0.1) with the prolonging of time. The mean stromal proportion of the 3-week models was as high as 75.32%. There was also a time-dependent increase in the relative total volume of epithelia in the model groups. The luminal area and the proportions of the luminal and epithelial volumes were obviously reduced in the model rats as compared with the sham operation controls. Pan-cytokeratin positive particles were located in epithelial cells, vimentins abundantly expressed in mesenchymocytes, and alpha-smooth muscle actins expressed around the lumen of the gland.</p><p><b>CONCLUSION</b>BPH induced by urogenital sinus implantation in rats is typically stromal hyperplasia, and the locations of related factors are similar to those in men with BPH.</p>

The causes of recurrent laryngeal nerve damage and prevention / 中华内分泌外科杂志

Objective To study the reasons and prevention of the hoarse voice after continuity-intact recurrent laryngeal nerve (RLN)operation without damage of RLN under naked eyes.Methods Data of 1871 patients undergoing thyroid surgery from Jan.2001 to Jan.2011 were retrospectly analyzed.919 patients had their RLN exposed,among whom 757 patients had bilateral RLN exposed.952 patients didn't have their RLN exposed in the surgery.Results A total of 1676 RLNs were exposed by the routine method and minimally invasive method.All the nerves were confirmed no damage and continuity intact under naked eyes.Hoarse voice occurred to 19patients after surgery,with the percentage of 2.12％ (19/897).The rate of hoarse voice in the non-exposed group was 5.46％ (52/952).The difference of horse voice between the RLN exposed group and non-exposed group had statistical significance(P ＜ 0.05).Conclusions RLN without damage under naked eyes and continuity intact doesn't mean no damage of electroneurophysiology.The rate of RLN damage in the exposed group was less than that in the non-exposed group.The major causes of hoarse voice may include misoperation,heat conduction and postoperative scar adhesion.The key to avoid RLN damage is prevention.

Correlation of tumor necrosis factor-alpha and interleukin-10 expression to acute rejection in complex tissue and serum of rats after laryngeal transplantation / 中国组织工程研究

BACKGROUND: It remains unclear whether proinflammatory factor, such as tumor necrosis factor-α (TNF-α), γ-interferon and anti-inflammatory cytokine, such as interleukin-10 (IL-10), interleukin-4 (IL-4) levels can change after laryngeal transplantation. OBJECTIVE: To explore the expression of TNF-α and IL-10 in different expressive tissue layers and its relationship during the acute rejection episodes, and to evaluate the role of TNF-α and IL-10 levels in serum for prediction of early acute rejection after laryngeal transplantation. METHODS: Laryngeal heterotopic transplantations were performed in Wistar and Sprague-Dawley rats. According to different dosages of immunodepressant, all recipients were divided into three groups: Group 0 mg, Group 5 mg, and Group 10 mg. Untreated Sprague-Dawley rats served as normal control group. RESULTS AND CONCLUSION: Changes in serum TNF-α and IL-10 levels at postoperation days 3, 7 and 11 were positively correlated with these expressions in the epithelium mucosa and submucosa at various time points after transplantation. These indicate that the high-antigenicity of graft mainly concentrates on the layers of mucosa and submucosa. TNF-α and IL-10 concentrations can serve as indexes for predicting acute rejection after laryngeal transplantation.

Endocrine therapy for breast cancer patients with ER and PR turning positive after neoadjuvant chemotherapy / 中华普通外科杂志

Objective To explore the effect of endocrine therapy in breast cancer patients whose estrogen receptor (ER) and progesterone receptor(PR) was preoperatively negative and turned positive after neoadjuvant chemotherapy. Methods The clinical experimental study was carried out in 97 cases of breast cancer which were divided into endocrine treatment group and control group. The follow-up time ranged from 15 to 60 months. Results In endocrine treatment group, 3 and 5-year disease-free survival were respectively 74.5% (38/51), 60.7% (31/51), and 3 and 5-year overall survival were respectively 80%(41/51), 74. 5% (38/51). In control group, 3 and 5-year disease-free survival were respectively 54.2% (26/46), 41.7%(20/46), and 3 and 5-year overall survival were 60.9%(28/46),50%(23/46),respectively. The corresponding values were significantly higher in endocrine treatment group than in control group(P＜0.05).Conclusions Remedy endocrine therapy improves the disease-free and overall survival rate in breast cancer patients with the expression of ER and PR turning positive after initial neoadjuvant chemotherapy.

Inhibition effect of China cobra venom active factor on endothelial cells and its biochemical mechanism / 中国生化药物杂志

Purpose To study the effect of China cobra venom active factor(CCVAF) from China cobra venom on endothelial cells and its mechanism.Methods MTT experiment was adopted to evaluate the effect of CCVAF on bovine arteria pulmonalis vascular endothelial cells(BAVEC).The Eosin-Coomassie brillient blue and rhodamine-phalloidin method was used for actin cytoskeleton.Flow cytometry for [Ca~(2+)]_i and spectrophotometry were used for lactate dehydrogenase(LDH) and nitrogen oxide(NO) levels in cell culture supernatant.Results CCVAF(0.625-20 μg/mL) inhibited the proliferation of BAVEC in dose-dependent manner,and IC50 of CCVAF on BAVEC was 2.45 μg/mL. After CCVAF and BAVEC coincubation, it was showed that regression of intercellular conjunctions and disorder of F-actin distribution occurred. The content of [Ca~(2+)]_i, [LDH] and [NO] increased respectively.Conclusion CCVAF can inhibit BAVEC proliferation and it maybe associated with the change of cytoskeleton and increasing of [Ca~(2+)]_i,[LDH] aod [NO].

Design, synthesis and vasorelaxant activity of R, S-1-(substituted phenyl)-4-3-(naphtha-1-yl-oxy)-2-hydroxypropyl-piperazine derivatives / 药学学报

According to the results of activity-structure relationship (SAR) studies of alpha1-adrenoceptor antagonists hydantoin-phenylpiperazine and benzimidazo-arypiperazine derivatves, to design and synthesize a series of novel phenylpiperazine alpha1-adrenoceptor antagonists with more potent vasorelaxant activity, active metabolites of naftopidil were used as lead compounds. Ten novel R,S-1-substituted phenyl-4-[3-(naphthal-yl-oxy)-2-hydroxy propyl]-piperazine were designed and synthesized, their vasorelaxant activity was evaluated by calculating inhibition rate of phenylephrine-induced vasocontration of rabbit artery trips. Five compounds exhibited vasorelaxant activity, and compound 16 showed significant vasorelaxant activity in vitro. At 0.01 and 1 micromol x L(-1), its inhibition rates were 7.03% and 22.72%, respectively. This compound possessed ideal vasorelaxant activity in vitro, and would be selected for further anti-hypertension evaluation in vivo. Moreover, by analyzing the primary activity and structure relationship of these compounds, it could be concluded that the SAR results of the reported phenylpiperazine alpha1-adrenoceptor antagonists could be used for reference in designing novel derivatives of naftopidil with optimal pharmacological properties.

Metabolites of R, S-1-(2-methoxyphenyl)-4-3-(naphtha-1-yl-oxy)-2-hydroxypropyl-piperazin in rat plasma / 药学学报

<p><b>AIM</b>To study the metabolites of R, S-1-(2-methoxypheyl)-4-[3-(naphthal-yl-oxy)-2-hydroxypropyl] -piperazine, (naftopidil, NAF), a novel antihypertensive drug in rat plasma.</p><p><b>METHODS</b>The rat plasma samples were analyzed by LC/MS after oral administration of NAF. According to MS relativity of metabolites and parent compound (NAF) and metabolic rule of compound with similar structure, the structure of potential metabolites were postulated. Phase I metabolites were identified by HPLC/MS and by comparison with authentic standards, phase II conjugates were indirectly identified with beta-D-glucuronidase in presence or absence of glucuronidase selective inhibitor D-saccharric acid beta-1,4-Lactone.</p><p><b>RESULTS</b>Phase I metabolites desmethyl-naftopidil (DMN), (phenyl) hydroxynaftopidil (PHN), (naphthyl) -hydroxy-naftopidil (NHN) were separated and identified in rat plasma by comparison with reference substances, phase II conjugates, NAF and NHN glucuronide conjugates were separated and tentatively identified by hydrolysis with glucuronidase, the aglycones, NAF and NHN, were identified in rat plasma.</p><p><b>CONCLUSION</b>The major metabolic pathway of NAF in rat plasma should be the hydroxylation of the phenyl or nephthyl moiety of NAF and demethylation of NAF. Therefore, (naphthyl) hydroxyl-metabolite and NAF followed by conjugation with beta-glueuronic acid.</p>