The clinical parameters of 1 000 patients undergoing spinal aesthesia were recorded and analyzed.Hypotension fulfilling the predefined criteria occurred in 173 patients.The logistic regression analysis revealed that the regression coefficients of height,weight and amount of fluid infusion during anesthesia were negative while those of age,emergency operation,hypertension/hypotension,heart disease,American Society of Anesthesiologists score,use of sedative drugs and sensory blocking level of anesthesia positive.The area of receiver operating characteristic was 0.905.This study contributes to the identification of patients with high risks for hypotension after spinal induction.

Objective:o prepare Danshensu liposomes and investigate drug release characteristics in vitro. Methods: Danshensu liposomes were prepared by a reverse-phase evaporation method. The encapsulation efficiency was used as the index, an orthogonal test was adopted to investigate the effect of concentration of soybean lecithin, ratio of lipid-Danshensu and pH value of solution on the preparation procedure of Danshensu liposomes. The particle size of the liposomes was also investigated by a transmission electron micro-scope ( TEM) . The concentration of Danshensu was determined by HPLC, and the difference of release characteristics in Danshensu li-posomes and Danshensu solution was measured by a dialysis method. Results:The optimum preparation technology was as follows:the concentration of soybean lecithin was 40 mg·ml-1 ,the ratio of drug-lipid was 1: 10,and the pH value of solution was 6. 6. The mor-phology of the prepared liposomes showed spheric structure with uniform diameter, and the average particle size was ( 174 ± 36 ) nm and the encapsulation efficiency was 38. 9%. The linear range of Danshensu was 2. 0-20. 0 mg·L-1(r=0. 9984). The drug release of liposomes in vitro was slower than that of free Danshensu solution in 24 h. Conclusion:Danshensu liposomes with fine morphology have sustained release property.

Objective:To study the protective effect and mechanism of paeoniflorin (pae) on myocardial injury in septic rats.Methods:Sprague-Dawley (SD) rats were randomly divided into 4 groups with 10 rats in each group. Rats were intraperitoneally injected with 1.4 ml normal saline and 1.4 ml 5% dimethyl sulfoxide (DMSO)solution independently in control group and DMSO group. Rats were intraperitoneally injected with 1.4 ml normal saline and 1.4 ml pae independently, then with 0.1 ml lipopolysaccharide (LPS) 1 hour later in sepsis group and pae group. Enzyme linked immunosorbent assay (ELISA) was used to detect serum cardiac troponin I (cTnI) levels and myocardial tissue tumor necrosis factor alpha (TNFα), interleukin(IL)-6, IL-1β, chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-X-C motif) ligand 2 (CXCL2), vascular cell adhesion molecule 1 (VCAM-1) levels. Evans blue (EB) method was used to detect the EB content of myocardial tissue. HE staining method was used to observe the pathological changes, real-time quantitative polymerase chain reaction (RT-qPCR) to detect mRNA expression levels of the above molecules, and Western-blot to detect vascular endothelium-cadherin (VE-cadherin), phosphorylated p38 mitogen-activated protein kinase (P-p38MAPK), phosphorylated Src protein (P-Src), Ras-Related C3 Botulinum Toxin Substrate 1 (Rac1) levels.Results:Compared with control group, cTnI level and the EB content in sepsis group increased significantly, and the myocardial inflammatory cell infiltration was obvious. The cTnI level and EB content in pae group were significantly reduced, and myocardial inflammatory cell infiltration was reduced [cTnI: (227.7±15.9)pg/ml vs. (312.9±17.9)pg/ml;EB: (13.2±2.3)μg/g vs. (23.8±2.9)μg/g; P<0.05]. Compared with control group, the levels of TNFα, IL-6, IL-1β, CXCL1, CXCL2, and VCAM-1 in sepsis group were increased. Compared with sepsis group, the above-mentioned molecular levels of pae group were significantly decreased [TNFα: (63.39±9.55)pg/ml vs. (126.54±19.17)pg/ml ;IL-6: (64.03±8.82)pg/ml vs. (85.60±9.52)pg/ml;IL-1β: (69.52±9.23)pg/ml vs. (130.45±15.10)pg/ml;CXCL1: (2 600.19±379.54)pg/ml vs. (4 903.89±533.42)pg/ml;CXCL2: (93.71±10.83)pg/ml vs. (127.24±13.92)pg/ml;VCAM-1: (112.22±13.49)pg/ml vs. (149.32±15.65)pg/ml, both P<0.05]. RT-qPCR results showed that the mRNA expressions of TNFα, IL-6, IL-1β, CXCL1, CXCL2 and VCAM-1 in the sepsis group were increased compared with the control group; Compared with sepsis group, the IL-6 mRNA (1.271±0.139 vs. 1.920±0.191, P<0.05), IL-1βmRNA (1.180±0.130 vs. 1.817±0.191, P<0.05), VCAM-1 mRNA (1.088±0.144 vs. 1.460±0.166, P<0.05) expression decreased significantly in the pae group. Compared with control group, the levels of P-p38MAPK and P-Src in sepsis group increased, and the level of VE-cadherin decreased. Compared with sepsis group, the levels of p38MAPK and P-p38MAPK in pae group were significantly decreased, and the level of VE-cadherin was increased (p38MAPK/β-actin: 1.125±0.078 vs. 1.520±0.164; P-p38MAPK protein: 1.639±0.133 vs. 2.112±0.222; both P<0.05). Conclusion:Paeoniflorin could improve the permeability of cardiac microvascular endothelium in sepsis rats and inhibit the secretion and expression of inflammation-related proteins and genes, which might be related to the inhibition of Src/VE-cadherin pathway by paeoniflorin.

Objective:To investigate the effect and mechanism of paeoniflorin on the permeability of cardiac microvascular endothelial cells (CMECs) in sepsis.Methods:Primary rat CMECs were isolated and cultured in vitro, and the cells in the logarithmic growth phase were used for experiments. Tetramethylazozolium colorimetry (MTT) was used to screen the safe and effective concentrations of paeoniflorin at 10, 20, and 40 μmol/L. The cells were divided into blank control group, lipopolysaccharide (LPS) group and low, medium and high concentration paeoniflorin pretreatment group. The cells in the blank control group were cultured in complete medium; the cells in the LPS group were challenged with LPS (1 mg/L) in complete medium; and the cells in the paeoniflorin pretreatment groups were pretreated with 10, 20, and 40 μmol/L paeoniflorin at 4 hours before LPS stimulation. The cells in each group were further cultured for 24 hours after LPS stimulation. The horseradish peroxidase (HRP) method was used to detect the permeability of rat CMECs. The enzyme-linked immunosorbent assay (ELISA) was used to detect the CXC chemokine ligand (CXCL1, CXCL2) levels in the cell supernatant. The real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the mRNA expressions of CXCL1 and CXCL2 in the cells. Western Blot was used to detect phosphorylated Src (p-Src), vascular endothelial-cadherin (VE-cadherin) and phosphorylated mitogen activated protein kinase (p-MAPK). Results:Compared with the blank control group, the permeability of rat CMECs in the LPS group was significantly increased. The cell permeability was improved to some extent after paeoniflorin pretreatment at different concentrations, and the improvement was most obvious in the 40 μmol/L paeoniflorin group, with statistically significant difference as compared with the LPS group ( A value: 1.61±0.07 vs. 2.13±0.06, P < 0.01). ELISA results showed that there were moderate amounts of CXCL1 and CXCL2 in the cell supernatant of rat CMECs in the blank control group. However, the secretion of CXCL1 and CXCL2 in the cell supernatant was increased significantly under the induction of LPS. After pretreatment with paeoniflorin at different concentrations, the secretion of CXCL1 and CXCL2 in the cell supernatant was significantly reduced. The most obvious inhibitory effect on CXCL1 was 40 μmol/L paeoniflorin, and the most obvious inhibition on CXCL2 was 20 μmol/L paeoniflorin, the differences were statistically significant as compared with the LPS group [CXCL1 (ng/L): 337.51±68.04 vs. 829.86±65.06, CXCL2 (ng/L): 4.48±0.11 vs. 9.41±0.70, both P < 0.01]. RT-qPCR results showed that the mRNA expressions of CXCL1 and CXCL2 in the rat CMECs were consistent with the ELISA results. LPS could increase mRNA expressions of CXCL1 and CXCL2 in the rat CMECs, and pretreatment with different concentrations of paeoniflorin could significantly reduce the mRNA expressions of CXCL1 and CXCL2. The 40 μmol/L paeoniflorin had the best inhibitory effect on CXCL1 mRNA expression, and the 20 μmol/L paeoniflorin had the best inhibitory effect on CXCL2 mRNA expression, the differences were statistically significant as compared with the LPS group [CXCL1 mRNA (2 -ΔΔCt): 0.543±0.004 vs. 0.812±0.089, CXCL2 mRNA (2 -ΔΔCt): 10.52±0.71 vs. 17.68±1.09, both P < 0.01]. Western Blot results showed that moderate amounts of p-Src, VE-cadherin and p-MAPK proteins were expressed in the rat CMECs in the blank control group. After LPS stimulation, the expressions of p-Src and p-MAPK proteins were increased significantly, while the expression of VE-cadherin protein was decreased significantly. After pretreatment with different concentrations of paeoniflorin, the expressions of p-Src and p-MAPK proteins in the cells were decreased to varying degrees, while the expression of VE-cadherin protein was increased, and 40 μmol/L paeoniflorin had the most obvious effect, the differences were statistically significant as compared with the LPS group [p-Src protein (p-Src/GAPDH): 1.02±0.09 vs. 1.29±0.05, p-MAPK proteins (p-MAPK/GAPDH): 0.24±0.02 vs. 0.62±0.02, VE-cadherin protein (VE-cadherin/GAPDH): 0.64±0.03 vs. 0.31±0.02, all P < 0.01]. Conclusion:Paeoniflorin can regulate the Src/VE-cadherin pathway in CMECs, inhibit the expression and secretion of inflammation-related proteins and chemokines, and improve the cell permeability of CMECs induced by LPS.

Objective To investigate the effect of Galangin on pyroptosis of bone marrow derived macrophages(BMDMs).Methods BMDMs were cultured in vitro and divided into blank control group,model group and Galangin group with different concentrations.Lipopolysaccharide(LPS)and adenosine triphosphate(ATP)were used to construct the pyroptosis model.The effect of different concentrations of Galangin on the proliferation of BMDMs was detected by cell counting Kit-8(CCK-8).The level of cysteinyl aspartate specific proteinase-1 p10 subunit(caspase-1 p10),interleukin-1β(IL-1β)in supernatant and intracellular nucleotide NOD-like receptor protein 3(NLRP3)were detected by Western blotting.IL-1β in supernatant was detected by enzyme-linked immunosorbent assay(ELISA).The cell death was observed by propidium iodide(PI)staining.High-throughput sequencing was used to compare the gene expression in the model group and Galangin groups at 20 μmol/L.Results There was no statistically significant difference between the 5,10,20,40,60,80 μmol/L Galangin groups on the proliferation level of BMDMs(all P>0.05),indicating that no significant effect of Galangin at 5,10,20,40,60,80 μmol/L was observed on the proliferation of BMDMs.So we selected Galangin at 5,10,20 μmol/L and treatment for 1,2 and 4 hours as the effects of different concentrations and time on the pyroptosis of BMDMs.Compared with blank control group,the expression of caspase-1 p10 and mature IL-1β protein and IL-1β in supernatant in model group were significantly increased(all P<0.05).Compared with model group,the expression of caspase-1 p10 and mature IL-1β protein and IL-1β in supernatant of Galangin at 5,10 and 20 μmol/L were significantly decreased[IL-1β protein expression(gray value):0.155±0.006,0.113±0.006,0.111±0.007 vs.1.000±0.000,caspase-1 p10 protein expression(gray value):0.207±0.044,0.160±0.008,0.082±0.008 vs.1.000±0.000,IL-1β(μg/L):99.80±10.36,85.21±8.78,26.53±4.56 vs.494.10±35.47,all P<0.05].There was no significant difference between the different concentration groups(all P>0.05),but with the extension of treatment time of Galangin,the inhibitory effect was enhanced.The inhibitory effect of Galangin at 20 μmol/L for 4 hours was the most obvious[IL-1β protein expression(gray value):0.186±0.004 vs.1.000±0.000,caspase-1 p10 protein expression(gray value):0.247±0.009 vs.1.000±0.000,IL-1β(μg/L):173.80±10.56 vs.653.80±76.02,all P<0.05].Treatment with 20 μmol/L Galangin for 4 hours could reduce the number of pyroptotic cell deaths(number of view:23.00±3.61 vs.67.67±15.63,P<0.05)and inhibited the expression of NLRP3 protein(gray value:0.178±0.025 vs.0.406±0.066,P<0.05).High-throughput sequencing showed that,compared with the model group,Galangin down-regulated the genes of Nlrp3,Nod2,IL-1β and up-regulated genes of Skp2(also known as Fbxl1),Fbxl20,Fbxl4,Fbxo32 and Fbxw7.Conclusion Galangin inhibited pyroptosis mediated by NLRP3 inflammasome in macrophages.

Objective To analyze the morphological and structural changes to pulmonary arterioles in rats induced by smoke exposure combined with Klebsiella infection,and to evaluate the severity of the pulmonary arteriolar lesions.Methods Pulmonary arteriolar images from lung sections of control and model rats treated with smoke exposure combined with Klebsiella infection were analyzed by qualitative and quantitative method.Victorian-blue-stained sections were used for the detection of pulmonary arteriolar muscularization,vascular wall thickness,vascular occlusion score,the intima thickness and media thickness of muscular arterioles,and neointima proliferation.Hematoxylin and eosin-stained sections were used for the observation and detection of inflammatory cell infiltration and plexiform lesions around arterioles.Van Gieson-stained sections were used for the observation of collagen fibers in the intima and detection of the percentage of collagen fiber area in the arteriolar wall.Based on the above analyses,the degree of pulmonary arteriolar pathology was rated according to Heath-Edwards criteria.Results For≤50 μm diameter arterioles,the percentage of non-muscular vessels was significantly decreased(P＜0.01),the percentage of muscular vessels was increased(P＜0.01),the percentage of partial muscular vessels was not significantly different(P＞0.05),the thicknesses of the non-muscular vessel walls and muscular vessel walls were significantly increased(P＜0.05,P＜0.01),and the occlusion scores of both non-muscular and muscular pulmonary arterioles were significantly increased in the model group compared with the Control group(P＜0.05,P＜0.01).For 50 μm＜diameter≤100 μm arterioles,the percentage of non-muscular vessels was significantly decreased(P＜0.05),the percentages of muscular vessels and partial muscular vessels were not significantly different(P＞0.05),the wall thickness and occlusion score of muscular vessels were significantly increased(P＜0.05),and the wall thickness and occlusion score of non-muscular vessels were not significantly different in the model group compared with the Control group(P＞0.05).Compared with the Control group,the model group showed significantly increased intimal thickness and media thickness and significantly increased perivascular inflammatory infiltration score in both muscular arterioles of≤50 μm diameter and 50 μm＜diameter≤100 μm(P＜0.05,P＜0.01).In the Control group(n=9),only one section with two neointimal lesions was found,and the degree of neointima proliferation was 1.61%.In the model group(n=10),five sections had neointima lesions,and the degree of neointima proliferation was 1.04%to 17.14%.No plexiform lesions were found in any section.For pulmonary arterioles with a diameter of≤100 μm,there was no change in the expression of intimal collagen fibers in the model group compared with the Control group,and there was no significant difference in the percentage of collagen fiber area in the vessel walls(P＞0.05).According to Heath-Edwards criteria,the pulmonary arteriole lesions in the model rats did not reach grade Ⅲ.Conclusions The model rats showed pathological manifestations such as pulmonary arteriolar muscularization,thickening of the intima and media,and mild to moderate inflammatory reactions around arterioles.The low amount of neointimal proliferation and collagen fibers in the vascular wall and the absence of plexiform lesions suggest that the model may be up to grade Ⅱ lesions,according to the Heath-Edwards criteria.

Renal colic caused by ureteral stone obstruction is the main cause for emergency treatment of patients with urinary tract stones, and drug expulsion therapy plays a vital role in the treatment.This article delves into a variety of drugs, including α1 adrenergic receptor blockers, β adrenergic receptor agonists, calcium channel blockers, prostaglandin synthetase inhibitors, corticosteroids, phosphodiesterase isoenzyme 5 inhibitors, and Chinese herbal medicines, exploring their mechanisms and applications in the treatment of distal ureteral stones.Currently, α1 adrenergic receptor blockers are still preferred for the treatment of distal ureteral stones due to their significant efficacy.It is worth noting that various drugs work through different mechanisms, and combining drugs with different mechanisms is expected to improve the efficiency of stone expulsion.This method may become the mainstream choice for stone expulsion drugs in the future.This article aims to provide new perspectives and ideas for the drug treatment of urinary tract stones.