Objective To observe the circadian blood pressure (BP) rhythms and the phase of heart circadian gene expression in adriamycin (ADR)-induced nephropathy rats,thus exploring the effect of circadian systems on circadian BP variation in nephrotic rats.Methods Sprague-Dawley (SD) male rats (8 weeks) were housed in a 12∶12 hour light/dark cycle in two weeks,and randomly divided into ADR group and control group.ADR rats were injected 6.5 mg/kg adriamycin via vein to establish nephrotic rats model two weeks later,while control rats were injected the equal volume of saline.Five rats in each group were implanted with the radio-telemetry into abdominal aortic.After seven days,systolic blood pressure (SBP),diastolic blood pressure (DBP),mean arterial pressure (MAP) and heart rate (HR) were recorded every one minute during 72 hours via radio-telemetry.Three rats in each group were sacrificed in six time points (zeitgeber time=02:00,06:00,10:00,14:00,18:00,22:00) to get the blood sample and heart tissue,respectively.The mRNA expressions of core clock gene CLOCK,BMAL1,Per1,Per2,Cry1 and Cry2 in heart issue were evaluated by the real-time quantitative PCR.The plasma levels of renin activity angiotensin Ⅱ and aldosterone were measured by radioimmunoassay.All the data were analyzed by a partial Fourier analysis and stepwise regression.Results (1) There was no significant difference in 24 h average of SBP,DBP and MAP between two groups.In control group,there was higher SBP (3.22 mmHg),DBP (1.16 mmHg) and MAP (3.19 mmHg) in dark period than those in light period,only SBP and MAP showing statistical difference (all P ＜ 0.05).However,SBP,DBP and MAP had no significant difference between dark and light in ADR group (all P ＞ 0.05).(2) Control rats had (8.0+24.0) h rhythm of SBP,and their DBP,MAP and HR appeared 24.0-hour normal circadian pattern (all P ＜ 0.05).In ADR group,the rhythm of SBP completely disappeared.And their DBP and MAP remained 24.0 h circadian rhythm,but the peak time advanced 1.5 h to 3.0 h compared with SD rats.(3) In SD controls,daily rhythms period of the core clock genes (CLOCK,BMAL1,Cry1,Cry2,Per1 and Per2) mRNA expression in the heart were (4.8+ 12.0) h,24.0 h,12.0 h,(12.0+24.0) h,(4.8+12.0) h and 12.0 h (all P ＜ 0.05),respectively.In ADR rats,the rhythm of CLOCK,BMAL1,Cry2,Per1 and Per2 mRNA completely disappeared (all P ＞ 0.05).The circadian rhythm of Cry1 mRNA remained,but the period was changed from 12.0 h to (4.8+6.0) h.(4) The plasma renin and aldosterone concentration presented 12.0 h and 24.0 h daily rhythms in SD rats (all P ＜ 0.05).These diurnal changes however completely disappeared in ADR rats (all P ＞ 0.05).Conclusions ADR nephrotic rats lose the circadian rhythm of BP with the disturbances of cardiac circadian clock system.The disrupted diurnal rhythm of the core clock genes (CLOCK,BMAL1,Cry2,Per1 and Per2) mRNA expression in the heart may regulate the pathological circadian rhythms of heart tissue,which is involved with disturbances of circadian rhythm of BP.

Objective To observe the clinical efficacy of Huajian-Badu membrane in the treatment of moderate and severe cancer pain. Methods The 80 malignant tumor patients with moderate to severe cancer pain from January 2016 to June 2017 in Tianjin University of Traditional Chinese Medicine First Teaching Hospital were recruited and randomly divided into the observation group and the control group, each of 40 cases. The control group were treated with Oxycodone Hydrochloride Prolonged-release Tablets, while the treatment group were treated with Huajian-Badu membrane on the basis of the treatment in control group. The pain relief, pain frequency, morphine consumption and quality of life (Karnofsky score), adverse reaction were evaluated between two groups before and after treatment. Results Compared with the control group, the total efficiency in the observation group was significantly higher (95.0％ vs. 80.0％, χ2=4.114, P=0.043). The frequency of breakthrough pain of two groups increased on the seventh and fourteenth treatment days(0.3 ± 0.6 times vs. 0.8 ± 0.7 times, t=-3.430 and 0.4 ± 0.6 times vs. 0.9 ± 0.8 times, t=-3.162), but the number of outbreaks of pain in the observation group significantly less than the control group (P<0.05 or P<0.01). The morphine injection dosage increased on the seventh and fourteenth treatment days (3.01 ± 4.28 g vs. 5.62 ± 6.37 g, t=-2.151 and 3.21 ± 4.32 g vs. 7.84 ± 7.76 g, t=-3.297), but the amount of the observtation group was significantly lower than that of control group (P<0.05 or P<0.01). The KPS score in the observation group increased significantly, and significantly higher than the control group on the seventh and fourteenth treatment days (73.0 ± 15.0 vs. 66.0 ± 12.0, t=2.305 and 77.0 ± 13.0 vs. 70.0 ± 15.0, t=2.230, P<0.05). The adverse reaction rate of the control group was 25％, while the the observation group was 20％. The difference between two groups was significant (χ2=0.287, P=0.592). Conclusions The Huajian-Badu membrane combined Oxycodone Hydrochloride Prolonged-release Tablets can improve the total effective rate of pain relief, reduce the number of outbreaks, reduce morphine consumption, improve patient KPS score of the patients with cancer pain.