The partial pressure of oxygen (PO2) in the tumor microenvironment directly affects tumor sensitivity to chemotherapy. In the present study, a lithium phthalocyanine probe was implanted into MCF-7 human breast cancer cells, followed by transplant of the cells into nude mice. The present study used an electron paramagnetic resonance (EPR) oximetry measuring technique to dynamically monitor PO2 in the tumor microenvironment prior to and following chemotherapy, and aimed to determine the precise time window in which the microenvironmental PO2 peaked following chemotherapy. The results indicated that PO2 was significantly higher in breast cancer compared with control (P<0.05). Following four cycles of chemotherapy, the activity of NADH dehydrogenase, succinate-cytochrome c reductase and cytochrome c oxidase in the mitochondria of cells was significantly reduced when compared with their activity prior to chemotherapy (P<0.05). Regional blood flow in tumor tissues undergoing chemotherapy was significantly lower than that prior to chemotherapy (P<0.05). The rate of cellular apoptosis in the PO2 peak-based chemotherapy group was significantly greater than that in the conventional chemotherapy group after two and four cycles of chemotherapy (P<0.05). Tumor volume in the PO2 peak-based chemotherapy group was significantly reduced compared with that in the 0.9% NaCl solution control and the conventional chemotherapy groups after four cycles of chemotherapy (P<0.05). The tumor inhibitory rate of the experimental group was significantly higher than that of the conventional chemotherapy group (P<0.01). In conclusion, the present study may provide guidance for the development of effective strategies depending on tumor-maximal response to chemotherapy in an oxygen-rich environment. Additionally, the present study aimed to establish a foundation for a clinical noninvasive assessment intended to guide treatment and formulate individual regimens, in order to improve cancer therapeutics, sensitivity monitoring and curative effect estimation.

Objective To discuss the technical skill and clinical safety of ultrasound-guided implantation of totally implantable venous access port ( TIVAP) via axillary vein. Methods We retrospectively analyzed the data of 40 breast cancer patients receiving chemotherapy via TIVAP ( research group ) in Department of Endocrine and Breast Surgery, First Affiliated Hospital of Chongqing Medical University from September to December 2016. Fifteen patients were implanted with TIVAP via left axillary vein, and the other 25 were implanted with TIVAP via right axillary vein. Another 50 patients who received TIVAP via internal jugular vein served as control group. The successful rate, proportion of the patients with ≤2 punctures, operation time, intraoperative and postoperative complications were compared between 2 groups. t test was used to compare the operation time, and Fisher exact probability method was used to compare the rate. Results The implantation of TIVAP via axillary vein or internal jugular vein were performed successfully in all cases, with the successful rate of 100% (40/40, 50/50). The operative time in research group was significantly longer than that in control group [(26±4) min vs (22±3) min, t=-5. 410, P<0. 001]. However, the proportion of the patients with ≤2 punctures, incidence of pneumothorax and incidence of arterial injury showed no significant difference between 2 groups [ research group vs control group: 97. 5% ( 39/40 ) vs 96. 0% (48/50), P=1. 000; 0(0/40) vs 2. 0% (1/50), P=1. 000; 0(0/40) vs 4. 0% (2/50), P=0. 501]. There were no significant differences in thrombosis rate and infection rate between 2 groups [research group vs control group:2. 5% (1/40) vs 0(0/50), P=0. 444;2. 5% (1/40) vs 2. 0% (1/50), P=1. 000]. Conclusion TIVAP implantation via axillary vein approach is a safe and effective technique with relatively low complication rate.

植入式静脉输液港留置时间长、并发症少、外形美观,近年来国内各大医院开始将其运用于临床,但目前国内医院对输液港相关并发症的预防和处理尚缺乏系统的相关知识,笔者对输液港植入时及临床使用中发生的主要并发症的原因、临床表现和处理措施进行综合分析,为医务工作者在临床上合理预防、及时发现及处理其相关并发症提供参考.

Objective To explore the clinical application and complication management of ultrasound-guided implantation of venous access port via axillary vein in breast cancer patients with chemotherapy.Methods From Sep.2016 to Jan.2017,50 breast cancer patients were implanted implantable venous access ports via the axillary vein under ultrasound guidance in the First Affiliated Hospital of Chongqing Medical University,among whom 25 cases with the left-side breast cancer,the other cases with right-side breast cancer.The effects of the application of implantation method and complication management were observed.Results The success rate of venous access ports via the axillary vein under ultrasound guidance was 98％(49/50).The operation time was (26±4) mins.The number of puncture ≤ 2 times was 96％ (48/50).The incidence of intraoperative complications including pneumothorax (0％,0/50),error arterial puncture rate 4％ (2/50),catheter ectopic incidence 2％(1/50),and intraoperative blood loss 2％(1/50).The long-term postoperative included pinch-off syndrome (POS) (0％,0/50),thromboembolism (2 ％,1/50),infection (2％,1/50) and catheter detachment (0％,0/50).Conclusion Ultrasound-guided implantation of venous access port via axillary vein has features of high success ratio,high safety,and low complication rate,which provides additional venous channel selection of port implantation.

目的：探讨甲状腺原发性乳头状癌合并鳞状细胞癌的诊断和治疗，降低误诊，延长患者生存时间提高生命质量。方法回顾性分析1例原发性甲状腺乳头状癌合并鳞状细胞癌的男性患者临床资料，结合相关文献进行分析，探讨其诊断和治疗。结果该患者行甲状腺全切除及颈部淋巴结清扫术后1个月行131I 核素治疗，术后3个月出现肿瘤局部区域复发和肺部转移，术后4个月局部复发病灶导致吞咽、呼吸困难，生命质量差，术后5个月死亡。结论原发性甲状腺乳头状癌合并鳞状细胞癌临床罕见、恶性程度高、预后差。临床诊断困难，其治疗手段应以手术治疗结合术后放疗为主，必要时行131I 治疗，以最大限度提高患者的生存率。

Background and purpose: Tumor microenvironment plays an important role in the introduction of foreign factors that mediate tumor acquired resistance. The antitumor effects of many chemotherapeutic agents depend on the level of oxygen pressure (pO2) in tumor microenvironment. This study aimed to evaluate electron paramagnetic resonance (EPR)-based monitoring on an oxygen-enriched tumor microenvironment to increase chemotherapeutic sensitivity. Methods: MCF-7 cells were used to establish human breast cancer in nude mice. EPR was used to directly measure pO2 level in vivo. Tumor tissues were collected, and mitochondrial activity was assayed on the basis of the kinetics of enzyme-catalyzed reactions. A laser Doppler monitor was used to detect regional blood flow. Tumor apoptotic rate was analyzed by flow cytometry. Results: The tumor volume decreased more evidently in the chemotherapy group with oxygen- enriched environment than that in the conventional chemotherapy group after the treatment was administered (P<0.01). After chemotherapy was completed, the apoptotic rate of tumor cells was significantly higher in the chemotherapy group with oxygen-enriched environment than that in the conventional chemotherapy group (P<0.001). This study examined the mechanism of pO2 changes in tumor microenvironment: This was related to the change of the balance between the oxygen consumption and the regional blood flow in the tumor tissues after chemotherapy. Conclusion: Based on the characteristics of pO2 changes in the tumor microenvironment after chemotherapy was completed, the selection of chemotherapy mode for the treatment in pO2 peak time window improves the sensitivity of chemotherapy, which provides a new idea for individualized chemotherapy in clinical applications.

1临床资料<br>　　女性，54岁，因“体检发现右乳成簇细小钙化4d”入院。体检：双乳、双腋窝、甲状腺及双颈侧区未见明显异常。乳腺钼靶示：右乳外上见较多成簇细小钙化。乳腺彩超：双乳腺增生。甲状腺彩超：甲状腺右叶可见一异常回声，大小约11 mm ×6 mm，边界可见，形态较规则，以低回声为主，内回声不均质，其内见较多团状及粗大强回声伴声影，加彩后其内见条状血流信号；进一步行甲状腺超声造影检查提示甲状腺癌不能除外。完善术前准备后行右乳钼靶导丝定位下钙化灶切除活检＋甲状腺手术，术中冰冻病理检查示：右乳腺组织增生活跃，原位癌不能除外，需待术后石蜡病检确诊；右甲状腺微小乳头状癌，遂行双侧甲状腺全切＋中央组淋巴结清扫。术后重庆医科大学病理检测中心诊断：右甲状腺微小乳头状癌；右乳原位癌（导管内癌）。补行右乳单纯乳房切除术。患者术后恢复可，顺利出院，长期口服左旋甲状腺素片（优甲乐，150μg， qd），门诊定期随访。

Exercise training offers cardioprotection against ischemia and reperfusion (I/R) injury. However, few essential signals have been identified to underscore the protection from injury. In the present study, we hypothesized that exercise-induced acceleration of myocardial tissue oxygenation recovery contributes to this protection. C57BL/6 mice (4 weeks old) were trained on treadmills for 45 min/day at a treading rate of 15 m/min for 8 weeks. At the end of 8-week exercise training, mice underwent 30-min left anterior descending coronary artery occlusion followed by 60-min or 24-h reperfusion. Electron paramagnetic resonance oximetry was performed to measure myocardial tissue oxygenation. Western immunoblotting analyses, gene transfection, and myography were examined. The oximetry study demonstrated that exercise markedly shortened myocardial tissue oxygenation recovery time following reperfusion. Exercise training up-regulated Kir6.1 protein expression (a subunit of ATP-sensitive K+ channel on vascular smooth muscle cells, VSMC sarc-KATP) and protected the heart from I/R injury. In vivo gene transfer of dominant negative Kir6.1AAA prolonged the recovery time and enlarged infarct size. In addition, transfection of Kir6.1AAA increased the stiffness and reduced the relaxation capacity in the vasculature. Together, our study demonstrated that exercise training up-regulated Kir6.1, improved tissue oxygenation recovery, and protected the heart against I/R injury. This exercise-induced cardioprotective mechanism may provide a potential therapeutic intervention targeting VSMC sarc-KATP channels and reperfusion recovery.

肿瘤患者因反复的血管穿刺和化疗药物本身的毒性易致穿刺血管形成血栓和静脉炎[1],严重的影响了患者的生活质量和生命安全。植入式静脉输液港( implantable venous access port, IVPA)是一种可植入皮下,长期留置在体内的静脉输液装置,通过使用无损伤针穿刺植入皮下输液港即可建立输液通道,可进行输注药物、补液、营养支持、输血等治疗。 IVPA最常见的植入方式有锁骨下静脉路径和颈内静脉路径,但因锁骨下路径易发生夹闭综合征( pinch-off syndrome)导致严重并发症,因此,临床多选择颈内静脉植入。2012年11月至2013年5月本院共完成超声引导下经颈内静脉途径输液港安置术50例,患者化疗结束后均顺利拔出输液装置。笔者将临床应用情况及体会总结如下。

Objective: The level of partial pressure of oxygen(PO2) in tumor microenvironment affects the tumor's sensitivity to chemothropy directly. Oxygen measuring technique from electron paramagnetic resonance(EPR) can offer the necessary technical to monitor the change of the PO2 in tumor microenvironment after chemothrapy uninvasively, real-time and accurately. Methods: EPR was used to measure the PO2 level directly in vivo. Tumor tissue was collected and the activity of mitochondria was assayed through kinetics of enzyme-catalyzed reactions. The laser doppler monitor was used to detect regional blood fl ow. Results: The data from the test of tissue oximetry demonstrated the initial PO2 in tumor microenvironment gradually increased to peak value at the fourth week, which was signifi cant higher than initial PO2 of tumor. The PO2 was higher in the experimental group after administration of doxorubicin(ADM). Then PO2 was gradually declined. The functions of mitochondrial nicotinamide adenine dinucleotide reduced dehydragenale, cytochrome C oxidase and succinate-cytochrome C reductase in tumor tissue were lower than those of the control group on the 4th day after chemotherapy. Conclusion: EPR oximtry measuring technique can be used to dynamically monitor the PO2 in tumor microenvironment during the chemotherapy and catch the time window of the peak value of PO2 in tumor microenvironment after chemotherapy exactly. The banlance change between oxygen consumption of mitochondria and the RBF may be one of themechanisms for PO2 change during ADM chemotherapy.

AIMS:Following ischemic injury, myocardial healing and remodeling occur with characteristic myofibroblast trans-differentiation and scar formation. The current study tests the hypothesis that hyperoxia and nitric oxide (NO) regulate TGF-β1 signaling in the post-ischemic myocardium. MAIN METHODS:C57BL/6 wild-type (WT), endothelial and inducible nitric oxide synthase knockout (eNOS(-/-) and iNOS(-/-)) mice were subjected to 30-min left anterior descending coronary artery occlusion followed by reperfusion. Myocardial tissue oxygenation was monitored with electron paramagnetic resonance oximetry. Protein expressions of TGF-β1, receptor-activated small mothers against decapentaplegic homolog (Smad), p21 and α-smooth muscle actin (α-SMA) were measured with enzyme-linked immunosorbent assay (ELISA), Western immunoblotting, and immunohistochemical staining. KEY FINDINGS:There was a hyperoxic state in the post-ischemic myocardial tissue. Protein expressions of total and active TGF-β1, p-Smad2/3 over t-Smad2/3 ratio, p21, and α-SMA were significantly increased in WT mice compared to Sham control. Knockout of eNOS or iNOS further increased protein expression of these signals. The expression of α-SMA was more abundant in the infarct of eNOS(-/-) and iNOS(-/-) mice than WT mice. A protein band indicating nitration of TGF-β type-II receptor (TGFβRII) was observed from WT heart. Carbogen (95% O2 plus 5% CO2) treatment increased the ratio of p-Smad2/t-Smad2, which was inhibited by 10006329 EUK (EUK134) and sodium nitroprusside (SNP). In conclusion, hyperoxia up-regulated and NO/ONOO(-) inhibited cardiac TGF-β1 signaling and myofibroblast trans-differentiation. SIGNIFICANCE:These findings may provide new insights in myocardial infarct healing and repair.

Modulation of purinergic signaling is critical to myocardial homeostasis. Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD-1; CD39) which converts the proinflammatory molecules ATP or ADP to AMP is a key regulator of purinergic modulation. However, the salutary effects of transgenic over expression of ENTPD-1 on myocardial response to ischemic injury have not been tested to date. Therefore we hypothesized that ENTPD-1 over expression affords myocardial protection from ischemia-reperfusion injury via specific cell signaling pathways. ENTPD-1 transgenic mice, which over express human ENTPDase-1, and wild-type (WT) littermates were subjected to either ex vivo or in vivo ischemia-reperfusion injury. Infarct size, inflammatory cell infiltrate and intracellular signaling molecule activation were evaluated. Infarct size was significantly reduced in ENTPD-1 versus WT hearts in both ex vivo and in vivo studies. Following ischemia-reperfusion injury, ENTPD-1 cardiac tissues demonstrated an increase in the phosphorylation of the cellular signaling molecule extracellular signal-regulated kinases 1/2 (ERK 1/2) and glycogen synthase kinase-3β (GSK-3β). Resistance to myocardial injury was abrogated by treatment with a non-selective adenosine receptor antagonist, 8-SPT or the more selective A(2B) adenosine receptor antagonist, MRS 1754, but not the A(1) selective antagonists, DPCPX. Additionally, treatment with the ERK 1/2 inhibitor PD98059 or the mitochondrial permeability transition pore opener, atractyloside, abrogated the cardiac protection provided by ENTPDase-1 expression. These results suggest that transgenic ENTPDase-1 expression preferentially conveys myocardial protection from ischemic injury via adenosine A(2B) receptor engagement and associated phosphorylation of the cellular protective signaling molecules, Akt, ERK 1/2 and GSK-3β that prevents detrimental opening of the mitochondrial permeability transition pore.

Objective:To explore the potential mechanism of the MCF-7 human breast carcinoma mouse model.Methods:Electron paramagnetic resonance(EPR) was used to measure the PO_2 level directly.Tumor tissues were collected and their mitochondrial activity was assayed using enzyme kinetics;the expression of NADH-DH,CcO,and SCR proteins were also detected by Western blot analysis.Results:The data from tissue oximetry demonstrated that tumor tissue was hypoxic compared with normal breast tissue[( 10.3±0.4) mmHg vs.(14.1±0.3) mmHg,P<0.05,n=6].Mitochondrial NADH-DH,CcO,and SCR function in the tumor tissue were lower than those in normal breast tissue at(177.16±2.01) nmol of reduced NADH/(mg protein·min) vs.(137.59±3.73) nmol reduced NADH/(mg protein·min),(14.81±0.89) vs.(19.53±0.35) nmol cyt c reduced/(mg protein·min) and(103.96±5.38) vs. (124.78±1.34) nmol cyt c oxidized/(mg protein·min),respectively(P<0.05).The expression of NADH-DH,CcO,and SCR proteins in the tumor tissue was lower than that in normal tissue.Conclusion:Detection of PO_2 level in breast carcinoma in mouse model with EPR directly proves that solid tumors have a hypoxic microenvironment.The complex enzyme activities were all decreased,which maybe related with the decrease in protein expression.

Aims: Late phase ischemic preconditioning ([PC) protects the heart against ischemia-reperfusion (I/R) injury. However, its effect on myocardial tissue oxygenation and related mechanism(s) is unknown. The aim of the current study is to determine whether LPC attenuates post-ischemic myocardial tissue hyperoxygenation through preserving mitochondrial oxygen metabolism.Main methods: C57BL/6 mice were subjected to 30 min coronary ligation followed by 60 min or 24 h reperfusion with or without LPC (3 cycles of 5 min 1/5 min R): Sham, LPC, I/R, and LPC + I/R group. Myocardial tissue Po-2 and redox status were measured with electron paramagnetic resonance (EPR) spectroscopy.Key findings: Upon reperfusion, tissue Po-2 rose significantly above the pre-ischemic level in the I/R mice (23.1 +/- 2.2 vs. 12.6 +/- 1.3 mm Hg, p<0.01). This hyperoxygenation was attenuated by LPC in the LPC + I/R mice (11.9 +/- 2.0 mm Hg, p <0.01). Activities of NADH dehydrogenase (NADH-DH), succinate-cytochrome c reductase (SCR) and cytochrome c oxidase (CcO) were preserved or increased in the LPC group, significantly reduced in the I/R group, and conserved in the LPC +I/R group. Manganese superoxide dismutase (Mn-SOD) protein expression was increased by LPC in the LPC and LPC + I/R mice compared to that in the Sham control (1.24 +/- 0.01 and 1.23 +/- 0.01, p<0.05). Tissue redox status was shifted to the oxidizing state with I/R (0.0268 +/- 0.0016/min) and was corrected by LPC in the LPC + I/R mice (0.0379 +/- 0.0023/min). Finally, LPC reduced the infarct size in the LPC + I/R mice (10.5 +/- 0.4% vs. 33.3 +/- 0.6%, p<0.05).Significance: Thus, LPC preserved mitochondrial oxygen metabolism, attenuated post-ischemic myocardial tissue hyperoxygenation, and reduced I/R injury. (C) 2010 Elsevier Inc. All rights reserved.

Ischemic postconditioning (IPOC) could be ineffective or even detrimental if the index ischemic duration is either too short or too long. The present study is to demonstrate that oxygen supply and metabolism defines a salvageable ischemic time window of IPOC in mice. C57BL/6 mice underwent coronary artery occlusion followed by reperfusion (I/R), with or without IPOC by three cycles of 10 s/10 s R/I. In vivo myocardial tissue oxygenation was monitored with electron paramagnetic resonance oximetry. Regional blood flow (RBF) was measured with a laser Doppler monitor. At the end of 60 min reperfusion, tissue from the risk area was collected, and mitochondrial enzyme activities were assayed. Tissue oximetry demonstrated that I/R induced a reperfusion hyperoxygenation state in the 30- and 45-min but not 15- and 60-min ischemia groups. IPOC attenuated the hyperoxygenation with 45 but not 30 min ischemia. RBF, eNOS phosphorylation, and mitochondrial enzyme activities were suppressed after I/R with different ischemic time, and IPOC afforded protection with 30 and 45 but not 60 min ischemia. Infarct size measurement indicated that IPOC reduced infarction with 30 and 45 min but not 60 min ischemia. Clearly, IPOC protected mouse heart with a defined ischemic time window between 30 and 45 min. This salvageable time window was accompanied by the improvement of RBF due to increased phosphorylated eNOS and the preservation of mitochondrial oxygen consumption due to conserved mitochondrial enzyme activities. Interestingly, this salvageable ischemic time window was mirrored by tissue hyperoxygenation status in the postischemic heart.

A high-fat diet (HFD) is associated with adipose inflammation, which contributes to key components of metabolic syndrome, including obesity and insulin resistance. The increased visceral adipose tissue mass associated with obesity is the result of hyperplasia and hypertrophy of adipocytes. To investigate the effects of exercise on HFD-induced metabolic disorders, male C57BL/6 mice were divided into four groups: SED (sedentary)-ND (normal diet), EX (exercise)-ND, SED-HFD, and EX-HFD. Exercise was performed on a motorized treadmill at 15 m/min, 40 min/day, and 5 day/wk for 8 wk. Exercise resulted in a decrease in abdominal fat contents and inflammation, improvements in glucose tolerance and insulin resistance, and enhancement of vascular constriction and relaxation responses. Exercise with or without HFD increased putative brown adipocyte progenitor cells in brown adipose tissue compared with groups with the same diet, with an increase in brown adipocyte-specific gene expression in brown and white adipose tissue. Exercise training enhanced in vitro differentiation of the preadipocytes from brown adipose depots into brown adipocytes and enhanced the expression of uncoupling protein 1. These findings suggest that exercise ameliorates high-fat diet-induced metabolic disorders and vascular dysfunction, and increases adipose progenitor cell population in brown adipose tissue, which might thereby contribute to enhanced functional brown adipose.