Objective:To study the effects of different doses of atorvastatin combined with valsartan on blood pressure variability (BPV) and circadian rhythm in patients with hypertension.Methods:Eighty patients with grade 2 and grade 3 hypertension from March 2018 to March 2019 in Hefei First People′s Hospital were divided into low-dose group (20 mg/d atorvastatin combined with valsartan) and high-dose group (40 mg/d atorvastatin combined with valsartan) according to the random number table method. The efficacy after 8 weeks of treatment was compared between the two groups. The BPV, circadian rhythm, vascular endothelial factors [nitric oxide (NO), endothelin (ET)], serum disease-related factors [human cartilage glycoprotein (YKL-40), soluble intercellular adhesion molecule-1(sICAM-1), folate] and blood lipids [total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C)] were recorded before treatment and 8 weeks after treatment, and the occurrence of adverse reactions during medicine was counted in the two group.Results:After 8 weeks of treatment, the total effective rate was 97.50%(39/40) in low-dose group and was 92.50%(37/40) in high-dose group, and there was no significant difference in the total effective rate between the two groups ( P>0.05). After 8 weeks of treatment, the 24 h SBPV, daytime SBPV, nighttime SBPV, 24 h DBPV, daytime DBPV and circadian rhythm in the two groups were significantly decreased compared with those before treatment, and the 24 h SBPV, daytime SBPV, daytime DBPV and circadian rhythm in high-dose group were significantly lower than those in low-dose group: (9.53 ± 1.73)% vs. (10.89 ± 1.98)%, (9.14 ± 1.90)% vs. (10.33 ± 2.07)%, (11.56 ± 2.78)% vs. (13.06 ± 3.16)%, (4.78 ± 1.56)% vs. (5.70 ± 1.81)%( P<0.05). After 8 weeks of treatment, the levels of NO, folate and HDL-C in the two groups were significantly increased compared with those before treatment, and the levels with in high-dose group were significantly higher than those in low-dose group: (67.16 ± 13.14) μmol/L vs.(60.53 ± 12.50) μmol/L, (14.94 ± 2.07) mmol/L vs.(13.83 ± 2.28) mmol/L, (1.42 ± 0.15) mmol/L vs. (1.31 ± 0.18)mmol/L ( P<0.05). The levels of ET, YKL-40, sICAM-1, TC, TG and LDL-C in the two groups were significantly decreased compared with those before treatment, and the levels in high-dose group were significantly lower than those in low-dose group: (33.63 ± 5.15) ng/L vs. (37.44 ± 5.13) ng/L, (32.68 ± 6.16) μg/L vs. (36.94 ± 6.03) μg/L, (203.78 ± 41.19) ng/L vs. (249.93 ± 50.81) ng/L, (6.78 ± 1.03) mmol/L vs. (7.38 ± 1.30) mmol/L, (2.88 ± 0.61) mmol/L vs. (3.39 ± 0.85) mmol/L, (3.14 ± 1.05) mmol/L vs. (3.85 ± 1.44) mmol/L ( P<0.05). Conclusions:Different doses of atorvastatin combined with valsartan are effective in the treatment of hypertension, but high dose of atorvastatin combined with valsartan has better effects on blood pressure variability and circadian rhythm, and can effectively improve vascular endothelial function.

ObjectiveTo observe the effects of Xibining （XBN） and adipose stem cell exosome （ADSC-Exos） in the cases of separate or joint application on cartilage degeneration and mitochondrial autophagy and explore its mechanism of action to improve knee osteoarthritis （KOA）. MethodSD rats were divided into a sham operation group （sham group）， a model group， an ADSC-Exos group （Exos group）， an XBN group， and an ADSC-Exos+XBN group （Exos+XBN group）. KOA model was established by using anterior cruciate ligament transection （ACLT）. The pain sensitivity status of rats was evaluated， and the degeneration degree of the knee joint and cartilage tissue was detected by Micro-CT and pathological staining. The expression of p62 and LC3B was observed by immunofluorescence， and the serum levels of TNF-α， IL-1β， IL-6， and IL-15 in rats were detected by ELISA. The Western blot was used to detect the protein expression levels of MMP-3， MMP-13， ADAMTS5， ColⅡ， TIMP， ACAN， PINK1， Parkin， p62， and LC3A/B. ResultCompared with the sham group， rats in the model group showed decreased cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， varying degrees of abrasion and loss of cartilage tissue， degeneration of cartilage tissue， elevated serum IL-1β， IL-6， IL-15， and TNF-α levels （P<0.01）， and increased protein expression of MMP-3， MMP-13， and ADAMTS5 in cartilage tissue. In addition， the protein expression of ColⅡ， TIMP1， and ACAN was decreased （P<0.01）. Compared with the model group， rats in each treatment group showed higher cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， reduced cartilage tissue degeneration， lower serum levels of IL-1β， IL-6， IL-15， and TNF-α （P<0.05，P<0.01）， decreased protein expression of MMP-3， MMP-13， and ADAMTS5， and higher protein expression of Cold， TIMP1， and ACAN in cartilage tissue （P<0.05，P<0.01）. Moreover， the changes were the most obvious in the Exos+XBN group. ConclusionBoth ADSCs-Exos and XBN can increase the level of mitochondrial autophagy in chondrocytes and delay cartilage tissue degeneration by promoting the expression of the PINK1/Parkin signaling pathway， and the combination of the two can enhance the therapeutic effect.