Objective To investigate the safety and efficacy of mechanical thrombectomy (MT) compared with In?tra-arterial Thrombolysis (IAT) treatment in patients with severe acute ischemic stroke (AIS) caused by large cerebral ar?tery occlusion. Method The patients with AIS caused by large cerebral artery occlusion and underwent MT or IAT from 2005 May to 2014 May was included. A retrospective analysis was conducted on the onset to emergency(OTE)time, emergency to acupuncture(ETA)time, acupuncture to recanalization (ATR) time, stroke severity as measured by the Na?tional Institutes of Health Stroke Scale (NIHSS) score, and site of arterial occlusion on magnetic resonance angiography (MRA). A comparison was made between MT and IAT patients in rates of recanalization, symptomatic intracranial bleed?ing (SIB), mortality, and functional outcome. Three-month favourable outcome was defined as a modified Rankin Scale (mRS) score≤2. Result One hundred and two AIS patients were treated with MT and 50 with IAT. There was no differ?ence between MT and IAT groups with regard to demographics, onset NIHSS score (13.37±6.95 vs. 12.70±6.11;P=0.572) and discharge NIHSS score (8.40 ± 6.69 vs. 7.53 ± 7.28, P= 0.522) and the change of NIHSS score (3.87 ± 7.14 vs. 4.26 ± 5.42, P=0.766). There were significantly differences between MT and IAT groups in the OTE time (Median 300 min vs. 120 min,Z=-5.704,P=0.000) , ATR time (Median 30 min vs. 65 min,Z=-5.011,P=0.001) ,recanalization (91.2%vs. 60.0%,P =0.01),the rate of AIB(21.7% vs. 36.0%,P =0.046),3-month mortality (16.6% vs. 26.0%,P =0.043). The above parameters were better in MT group than in the IAT group. There were no significant differences between MT and IAT groups in the rate of SIB (12% vs. 16%,P =0.055), the NIHSS change(Median 3 vs. 4,Z =-0.236,P =0.823) and mRS score on 90d ( 48.2%vs. 46.0%, P=0.823). MT patients had significantly higher percentages of stent use (22.5%vs. 8%,P=0.018) . The Recanalization for ICA(81.8%vs. 55.6%,P=0.048),BA(93.1%vs. 55.6%,P=0.032)and MCA( 97.5% vs. 60.0%,P =0.026)was higher in MT group than in IAT group .The SIB rate for ICA(13.8% vs. 33.3%,P =0.000),BA(13.8%vs. 33.3%,P=0.000)was lower in MT group than in IAT group . The mortality rate of was significant?ly lower in MT than in IAT group for MCA (2.5%vs. 20.0%,P=0.000) . the good outcome rate for BA was higher in MT group than in IAT group(41.3%vs. 22.2%,P﹤0.01). Conclusions Compared to IAT,MT can provide broader time win?dow,higher recanalization rate and better outcome in patients with severe acute ischemic stroke (AIS) caused by large ce?rebral artery occlusion.

Objective:To evaluate the clinical efficacy of intermediate frequency pulse electrical stimulation combined with TCM directional drug penetration therapy in the treatment of patients with lumbar spinal stenosis.Methods:Randomized controlled trial. Totally 90 patients with lumbar spinal stenosis who were treated between July 2018 and December 2021 in the hospital were selected according to randomized controlled trial design, and they were divided into the two groups through the random number table method, with 45 cases in each group. The control group was given non-steroidal anti-inflammatory drugs+conventional intermittent traction + intermediate frequency pulse electrical stimulation, and the combined group was treated with TCM directional drug penetration therapy on the basis of the control group. Both groups were continuously treated for 1 month. The TCM syndromes were scored before and after treatment, and Visual Analogue Scale (VAS) was used to evaluate the pain degree. Japanese Orthopedic Association (JOA) and Oswestry Disability Index (ODI) were applied to assess the dysfunction degree and quality of life, and the clinical efficacy was assessed.Results:The total effective rate was 95.56% (43/45) in combined group and was 82.22% (37/45) in control group, with statistical significance ( χ2=4.05, P=0.044). The scores of lumbago pain, articular soreness, knee soreness and weakness and impaired activity and total score in combined group after treatment were lower than those in the control group ( t=18.40, 15.81, 15.40, 26.50, 59.575, P<0.01), and the JOA score was higher than that of the control group ( t=5.62, P<0.01), while the ODI score was lower than that of the control group ( t=9.43, P<0.01). The time-point effect and between-group effect of VAS score in combined group were lower than those in the control group with the extension of time ( F=240.00, 17.19, P<0.01), and there was an interaction effect between decrease and treatment method ( F=6.66, P<0.01). Conclusion:Intermediate frequency pulse electrical stimulation combined with TCM directional drug penetration therapy is helpful to relieve the pain, improve the lumbar dysfunction degree and enhance the quality of life and clinical efficacy in patients with lumbar spinal stenosis.

Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia, which results in atherosclerosis and cardiovascular disease (CVD). ATP-citrate lyase (ACLY) is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle (TCA cycle) to acetyl-CoA in the cytoplasm. Therefore, ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo lipogenesis. In this study, we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor, and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC₅₀ = 5.31 ± 1.2 μmol/L in vitro. 326E treatment reduced de novo lipogenesis, and increased cholesterol efflux in vitro and in vivo. 326E was rapidly absorbed after oral administration, exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid (BA) used for hypercholesterolemia. Chronic 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of hyperlipidemia. Once daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE^-/- mice to a greater extent than that of BA treatment. Taken together, our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia.