Dexmedetomidine alleviates doxorubicin cardiotoxicity by inhibiting mitochondrial reactive oxygen species generation.

Cardiotoxicity largely limits the application of doxorubicin (Dox) for cancer treatment. Dexmedetomidine (Dex), a selective agonist of α2-adrenergic receptor, has been suggested to exert cardioprotection against myocardial injury. However, the effect and underlying mechanisms of Dex on Dox cardiotoxicity remain unknown. In this study, C57BL/6 mice were treated with Dox followed by Dex administration. Cardiomyocytes were co-incubated with Dox and Dex in vitro. The results showed that Dex markedly attenuated cardiac dysfunction induced by Dox. TUNEL staining exhibited that Dex inhibited Dox-induced cardiomyocyte apoptosis in myocardium. Moreover, the expression of anti-apoptotic protein Bcl-2 was increased, whereas the expression of pro-apoptotic protein Bax was decreased by Dex. Dox-induced the increase of reactive oxygen species (ROS), superoxide anion, and mitochondrial ROS (mROS) generation in myocardial tissues were significantly inhibited after Dex administration. In in vitro study, it was further confirmed that Dex prevented Dox-induced cardiomyocyte apoptosis and injury. However, the stimulation of mROS generation reversed the effect of Dex in cardiomyocytes. Mechanically, Dex blocked Dox-induced the ubiquitination of peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), leading to the restoration of PGC-1α and downstream oxidative stress-protective molecules uncoupling protein 2 and manganese-dependent superoxide dismutase expression. Taken together, this study demonstrates that Dex exerts cardioprotection against Dox cardiotoxicity by attenuating mitochondrial dysfunction, oxidative stress, and cardiomyocyte apoptosis via inhibiting PGC-1α-signaling pathway inactivation. This suggests that Dex may be a potential therapeutic strategy for Dox cardiotoxicity treatment.

Receptor status testing and its influence on following treatment selection in breast cancer patients with loco-regional recurrence / 上海交通大学学报（医学版）

Objective: To analyze the concordance rates of estrogen receptor (ER),progesterone receptor (PR),human epidermal growth factor receptor-2 (HER-2),and Ki67 statuses between the primary and loco-regional recurrence (LRR) lesions and its influence on the following treatment in breast cancer patients. Methods: The breast cancer patients undergoing surgery in Comprehensive Breast Health Center,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from January 2009 to September 2018,who were reported recurrence only in loco-regional site were retrospectively analyzed. ER,PR,HER-2,and Ki67 statuses were detected in primary and LRR lesions. Concordance rates and their influence on following treatment were further analyzed. Results: A total of 7 823 breast cancer patients received surgery,among whom 106 cases experienced LRR without distant metastasis. There were 56 patients having full information about ER,PR,HER-2,and Ki67 statuses of LRR lesions,with the positive rates of 48.2%,25.0%,35.2%,and 81.5%,respectively. Concordance rates of ER,PR,HER-2,and Ki67 between primary and LRR lesions were 76.8%,76.8%,89.1% and 77.8%,with κ values at 0.538,0.469,0.729,and 0.402,respectively. Hormone receptor (ER or PR) (14 cases) and/or HER-2 (6 cases) statuses were altered in 18 patients. The hormone receptor status changed from positive to negative in 9 cases,of which 4 cases did not receive following endocrine therapy. The HER-2 status changed from negative to positive in 4 patients,and 1 of them received following anti-HER-2 targeted therapy. Conclusion: The concordance rates between primary and LRR breast cancer lesions of ER,PR,and Ki67 are moderate,and the concordance rate of HER-2 is high. Changes in receptor status in LRR lesions may affect the choice of following treatment options.

Change of macular microperimetry in diabetes patients without diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the macular function of patients with diabetes mellitus(DM)who had no diabetic retinopathy(DR). <p>METHODS: Totally 140 eyes of 70 subjects with diabetes who had no vision disorders and fundus abnormalities(DM group)and 160 eyes of 80 normal subjects(control group)were examined. In DM group, from 20 to 30 were 8 patients(16 eyes), from 30 to 40 were 18 patients(36 eyes), from 40 to 50 were 24 patients(48 eyes), over 50 were 20 patients(40 eyes). In control group, there were 20 people in each age stages. Retinal imaging and macular microperimetry were measured by MP-l Microperimeter. The mean retinal light sensitivity(MS)in the central 20°, fixation stability and fixation position in the central 2° and 4° were recorded. <p>RESULTS: With the ages from 20 to 30, the MS of DM group and control group were 15.32±1.82, 19.41±0.32dB; from 30 to 40, the MS were 14.93±2.11, 18.92±0.73dB; from 40 to 50, the MS were 14.55±2.84, 18.21±0.53dB; over 50 years, the MS were 13.21±2.25, 17.14±1.21dB; respectively,the difference was all statistically significant between the two groups with the same age(<i>P</i>>0.05). All subjects were central fixation. Among 160 eyes of control group, fixation was stable in 124 eyes(77.5%), relative unstable in 36 eyes(22.5%); among 140 eyes of DM group, fixation was stable in 109 eyes(77.9%), relative unstable in 31 eyes(22.1%), the difference was statistically significant(<i>χ</i>²=0.00549, <i>P</i>>0.05). <p>CONCLUSION: The macular function and the MS in the central 20° had been damaged before fundus morphological abnormalities were detected in patients with diabetes. However, compared with control group, the fixation position and fixation stability did not changed significantly in patients with diabetes.

Relationship Between Monocyte to HDL-Cholesterol Ratio and Thrombus Burden in Patients With ST-segment Elevation Myocardial Infarction / 中国循环杂志

Objective: To analyze the relationship between monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) in patients with ST-segment elevation myocardial infarction(STEMI) in order to explore the predictive value of MHR in thrombus burden level in STEMI patients. Methods: A total of 357 STEMI patients treated in our hospital from 2015-01 to 2016-12 were enrolled. Thrombus burden was confirmed by angiography and the patients were divided into 2 groups: Low thrombus burden group, n=156 and High thrombus burden group, n=201. MHR was compared between 2 groups; the predictive value of MHR in thrombus burden level was studied by multivariate Logistic regression analysis and ROC curve assessment. Results: MHR was higher in High thrombus burden group than that in Low thrombus burden group [M (Q1, Q3) 25.4 (13.5, 44.6) vs 16.0 (9.2, 22.1)], P<0.001; multivariate Logistic regression analysis indicated that MHR was the independent predictor for high thrombus burden occurrence (OR=1.067, 95％ CI 1.031-1.105), P<0.001; the area under ROC curve for MHR was 0.688 in STEMI patients. Conclusion: MHR was the independent predictor for high thrombus burden occurrence in STEMI patients.

Electroacupoint stimulation for postoperative nausea and vomiting in patients undergoing supratentorial craniotomy.

OBJECTS: We evaluated the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) at the P6 acupoint for prevention of postoperative nausea and vomiting in patients undergoing supratentorial craniotomy. METHODS: The study population was patients aged 20 to 60 years who underwent supratentorial craniotomy under general anesthesia. Exclusion criteria were obesity, diabetes mellitus, and a history of motion sickness, postoperative nausea and vomiting, or smoking. Patients were randomized into 2 groups: stimulation and control. In the former, transcutaneous stimulation electrodes were placed at the right P6 acupoint. In controls, electrodes were positioned at a nonacupoint site. Patients received a standard general anesthesia. Ondansetron was given as a routine antiemetic treatment for each patient before skin closure. Postoperatively, metoclopramide (10 mg, i.v.) was administered as a rescue antiemetic. RESULT: Forty patients received TEAS and 40 were controls. In the TEAS group, 18% of patients had nausea compared with 37% of the controls. The cumulative prevalence of vomiting was 12.5% with acustimulation and 32.5% in controls (P<0.05). The prevalence of nausea, vomiting was significantly lower with TEAS at the P6 acupoint. CONCLUSIONS: TEAS at the P6 meridian points is an effective adjunct to standard antiemetic drug therapy for prevention of nausea and vomiting in patients undergoing supratentorial craniotomy.

Hydroxyapatite modified titanium promotes superior adhension and proliferation of corneal fibroblast in comparison with pure titanium / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To determine whether hydroxyapatite modified titanium promotes superior adhension and proliferation of rabbit corneal fibroblast in comparison with pure titanium.METHODS: We used bioactive hydroxyapatite to modify titanium surfaces. Fourth passage fibroblasts of rabbit cornea were seeded on hydroxyapatite modified titanium surfaces, pure titanium and glass surfaces. Cell adhension, proliferation and morphology were detected at 24 hours, 48 hours, and 72hours using a acridine orange stain. Further studies of cell morphology were performed using scanning electron microscopy.RESULT: Ceil counts were significantly greater on hydroxyapatite modified titanium surfaces at each time point(P＜0.05).At 24 hours, cell spreading was greater on hydroxyapatite-coated titanium and glass than on the pure titanium. At 72 hours, compared with pure titanium and glass surfaces, the cells on hydroxyapatite modified titanium surfaces had greater spreading area and longer stress fibers.CONCLUSIONS: Hydroxyapatite modified titanium promotes superior adhension and proliferation of rabbit corneal fibroblast in comparison with pure titanium.