OBJECTIVE:To observe the clinical efficacy and safety of flunarizine combined with salvianolate in the treatment of acute migraine. METHODS:A total of 72 patients with acute migraine were randomly divided into control group(36 cases)and observation group (36 cases). Based on routine treatment,control group was given Flunarizine hydrochloride capsules orally,10 mg for 65 year-old and below once a day,5 mg for more than 65 year-old once a day. Observation group was additionally given Flunarizine hydrochloride for injection 200 mg intravenously,once a day,on the basis of control group. Both groups were treated contineously till cured or for 2 weeks. Clinical efficacy,onset time,recovery time,VAS score,frequency and duration of head-ache attack,ADR were observed in 2 groups. RESULTS:In the course of treatment,the two groups did not terminate and fall off, and all of them completed the treatment. The total response rate(97.22%)of observation group was significantly higher than that (86.11%)of control group;onset time and recovery time of observation group were both shorter than those of control group,with statistical significance (P<0.05). Before treatment,there was no statistical significance in VAS score,frequency or duration of headache attack between 2 groups (P>0.05). After treatment,VAS score,frequency and duration of headache attack in 2 groups were all significantly lower than before,and the observation group was significantly lower than the control group,with statistical significance (P<0.05). There was no statistical significance in the incidence of ADR between 2 groups (P>0.05). CONCLU-SIONS:Based on routine treatment,flunarizine hydrochloride capsules combined with Salvianolate injection show significant effica-cy for acute migraine with good safety.

Objective: To investigate the role and mechanism of Hydroxysafflor yellow A (HSYA) in the calcification of vascular smooth muscle cells (VSMC) induced by β-glycerol phosphate (β-GP). Methods: VSMC were cultured with 10% fetal bovine serum+1% double anti-high glucose DMEM medium at 37℃ and 5%CO₂ incubator, and were subcultured according to cell growth density at 1∶4 ratio. The cells were divided into three groups: control group (NC), high-phosphate-induced calcification (HP) group, and HSYA intervention (HSYA) group. The Calcium deposition amount was measured by alizarin red staining and calcium determination kit. The expressions of ALP, RUNX2, RANKL, α-SMA and inflammation indicators TLR4, TNF-α, IL-8 were detected by Western blotting method; Western blotting was also used to detect calcification index alkaline phosphatase (ALP) and Runt-related transcription factor 2 (RUNX2). Nuclear factor kappa B receptor activating factor ligand(RANKL), α-smooth muscle actin (α-SMA), and the expressions of TLR4/NF-κB pathway and inflammatory response-related indicators Toll-like receptor 4 (TLR4), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α). The nuclear protein and cytoplasmic proteins were respectively extracted. The expressions of p65 in nucleus and cytoplasm, as well as the expressions of p65 and phosphorylated p65 in total proteins were detected by Western blotting method. Superoxide dismutase (SOD) and malondialdehyde (MDA) kit were used to detect the content of antioxidant enzymes and oxidation end products in cells. Results: Western blotting showed that the expressions of ALP, RUNX2 and RANKL in HSYA group were significantly lower than that in HP group. The expression of α-SMA was increased than that of HP group (all P<0.01). The expression levels of TLR4, TNF-α, IL-8 and p-NF-κB/p65 in HSYA group were decreased compared with that in the HP group, and p65 was decreased in nucleus and increased in cytoplasm (all P<0.05). SOD content in HSYA group was significantly higher than that in HP group, and MDA content was significantly lower than that in HP group (all P<0.01). Conclusions HSYA can reduce calcification and calcium deposition of vascular smooth muscle cells induced by high phosphorus. The mechanism is related to the inhibition of the activation of TLR4/NF-κB pathway and the inhibition of oxidative stress.

Objective To investigate the possible mechanism of sclerostin/Lrp4 in calcification of VSMC induced by high phosphorus and the protective effect of Ginkgo biloba extract.Methods Aortic vascular smooth muscle cells (VSMCs) of SD rats were extracted and identified.VSMCs were divided into normal control group,high phosphorus induced calcification group (10 mmol/L β-glycerophosphate+50 μg/ml ascorbic acid),and high phosphorus induced calcification+Ginkgo biloba extract intervention group (10 mmol/L β-glycerophosphate+50 μg/ml ascorbic acid+0.5 mg/ml GBE),cultured in different mediums for 14 days.Vonkossa staining and alizarin red staining were used to detect the calcification of VSMCs.The mRNA level of BGP was detected by real time PCR,and the protein expressions of sclerostin and Lrp4 were detected by Western blot.Results Compared with normal control group,vonkossa staining and alizarin red staining showed significant calcium deposition in calcification group.Compared with calcification group,calcium salt deposition was significantly reduced in GBE treatment group.Real time PCR results showed β-catenin and BGP mRNA expressions in VSMC calcification group were higher than those in normal control group (P＜ 0.05).mRNA expressions of β-catenin and BGP in GBE treatment group were lower than those in calcification group (all P ＜ 0.05).Compared with normal control group,the protein expression of sclerostin was increased,but the protein expression of Lrp4 was decreased in calcified group (all P ＜ 0.05).Compared with calcification group,the protein expression of sclerostin decreased and the protein expression of Lrp4 increased in GBE treatment group (all P ＜ 0.05).Conclusions High phosphorus can induce VSMC calcification by activating Wn/β-catenin signaling pathway.Sclerostin/Lrp4 is involved in hyperphosphine-induced VSMC calcification.GBE can reduce the high phosphorus induced VSMC calcification by regulating the Wnt/β-catenin signaling pathway.

Objective To investigate the influence mechanism of Cordyceps sinensis (CS) on β-glycerophosphate-induced vascular smooth muscle cell (VSMC) calcification.Methods The effect of CS on VSMC cell viability was detected by CCK-8.The cellular models of rat VSMC calcification were established by treating with β-glycerophosphate (β-GP,10 mmol/L);then CS (10 mg/L),autophagy inhibitor 3-methyladenine (3-MA,5 mmol/L),and AMPK inhibitor compound C (CC,10 μmol/L) were added to the cell cultures.There were a total of 5 experiment groups:VSMC cultured in normal medium (Control),VSMC treated with β-GP,VSMC treated with β-GP and CS,VSMC treated with 3-MA,β-GP and CS,and VSMC treated with CC,β-GP and CS.The calcium nodules and calcium content were examined with alizarin red S staining and the O-cresolphthaleincomplexone method,respectively.The autophagosomes within the VSMC were observed using transmission electron microscope (TEM).Immunofluorescence showed the accumulation of microtubule-associated protein 1 light chain 3 (LC3) puncta.In addition,levels of osteogenic related proteins,autophagy related proteins,and AMPK/mTOR pathway related proteins were evaluated by Western blotting.Results CS increased the number of autophagosomes and the accumulation of LC3 puncta within VSMC.It also upregulated the protein levels of LC3 Ⅱ/LC3 Ⅰ,beclin1,α-SMA,and p-AMPK;whereas,the protein levels of Runx2 and p-mTOR,as well as calcium nodules and calcium content were reduced (all P ＜ 0.01).When the cells were pretreated with 3-MA before treating with β-GP and CS,the autophagosomes,accumulation of LC3 puncta,and protein levels of LC3 Ⅱ/LC3 Ⅰ,beclinl,and α-SMA were decreased (all P ＜ 0.01);however,the protein level of Runx2,and the calcium nodules and calcium content were increased (all P ＜ 0.01).Nevertheless,when the cells were pretreated with CC before giving β-GP and CS,the autophagosomes,the accumulation of LC3 puncta,and the expression levels of p-AMPK,LC3 Ⅱ/LC3 Ⅰ,beclin1,and α-SMA were significantly down-regulated (all P ＜ 0.01);whereas,the expression levels of Runx2 and p-mTOR,as well as calcium nodules and calcium content were increased (all P ＜ 0.01).Conclusions CS can effectively alleviate β-GP-induced VSMC calcification,which may be due to the activation of autophagy by AMPK/mTOR signaling pathway.

Objective:To investigate the impact of cleavage factor Im25(CFIm25)on VSMCs-specific knockdown in the context of hyperlipidemia.Methods:Mice models were constructed with specific knockout of CFIm25 in VSMCs(CFIm25f/+ TaglnCre)and control mice(TaglnCre).The mice were fed a normal diet or high-fat diet(HFD)for 18 weeks and their body weight changes were monitored.ELISA was used to measure serum total cholesterol(TC), triacylglycerol(TG), high-density lipoprotein(HDL-C)and low-density lipoprotein(LDL-C)levels.The extent of aortic lipid deposition in mice was assessed by oil red O staining.Results:During the feeding of a high-fat diet, CFIm25f/+ TaglnCre mice showed a significant increase in body weight compared to the control group[Male(1.01±0.06)g and(0.87±0.31)g, t=7.53, P<0.05; Female: (0.64±0.02)g and(0.35±0.04)g, t=9.68, P<0.05].After 18 weeks of high-fat diet feeding, CFIm25f/+ TaglnCre mice had significantly higher levels of TC[(6.80±0.35)mmol/L and(3.76±0.87)mmol/L, t=5.63, P=0.004], TG[(0.97±0.21)mmol/L and(0.42±0.10)mmol/L, t=4.08, P=0.015], and LDL-C[(5.20±0.30)mmol/L and(2.00±0.98)mmol/L, t=5.40, P=0.006]compared to the TaglnCre group.Specifically, TC levels increased by 80.72%, TG increased by 132.79%, and LDL-C increased by 160.32%.There was a significant increase in aorta lipid deposition and atherosclerotic plaque area in CFIm25f/+ TaglnCre mice( P<0.05). Conclusions:The research indicated that VSMCs-specific CFIm25 knockdown in mice further worsened hyperlipidemia and atherosclerotic lesions.

Intrauterine adhesion (IUA) is caused by damage of the basal layer of endometrium, which leads to fibrosis of the endometrium and the formation of adhesion, resulting in partial or complete occlusion of the uterine cavity, abnormal menstruation, infertility or recurrent miscarriage. The prevalence of IUA in women has been increasing in recent years, and the high recurrence rate of moderate to severe IUA makes IUA treatment more challenging. Iatrogenic endometrial injury is the main cause of IUA. However, the incidence of IUA and the severity of IUA vary among patients who have received similar uterine operations, suggesting that there may be other synergistic factors in the development of IUA. There is a certain correlation between the pathogenesis and the microbiota of the gential tract. In many IUA patients, it has been observed that the probiotics such as Lactobacillus in the vagina is significant reduced, and the pathogenic bacteria such as Gardnerella and Prevotella are excessive growth. The reproductive tract microbiota can be involved in the development and progression of IUA via impacting immune function and metabolism.
Humans ; Female