Objective To investigate whether Andrographolide(AG)can alleviate intestinal injury in sepsis by ac-tivating the SLC7A11/GPX4 axis in ferroptosis.Methods Forty rats were randomly divided into sham group(sham group),sepsis group(CLP group),AG low,medium and high dose groups(5,10 and 20 mg/kg).HE staining was used to observe the pathological changes of Intestinal tract.ELISA method was used to determine Inter-leukin 6(IL-6),tumour necrosis factor α(TNF-α),intestinal fatty acid binding protein(I-FABP),D-lactate content.The mechanism of ferroptosis was explored with AG high dose group(AG20 group),forty rats were ran-domly divided into sham group,CLP group,ferroptosis inhibitor(Fer-1)group,AG20+Fer-1 group.HE staining and transmission electron microscopy were used to observe the pathological changes of Intestinal tract.The kits were used to determine oxidative stress MDA,GSH levels and Fe3+content.Western blot was used to detect the protein levels of solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),and ferritin heavy poly-peptide 1(FTH-1).Results Compared with the sham group,the CLP group showed severe morphological damage to the small intestine,with significantly higher levels of inflammation,I-FABP and D-lactate(all P＜0.05),the AG group reversed these changes in a concentration-dependent manner(all P＜0.05).Compared with the CLP group,the AG20 and Fer-1 groups showed improved pathological damage to the small intestine,with lower levels of MDA and Fe3+and higher levels of GSH,SLC7A11,GPX4 and FTH-1 protein expression increased(all P＜0.05),and pathological injury and oxidative stress were reduced in the AG20+Fer-1 group,and SLC7A11,GPX4 and FTH-1 protein expression increased more significantly(all P＜0.05).Conclusion The mechanism by which AG attenuates intestinal injury in sepsis may be related to SLC7A11/GPX4 axis activation in ferroptosis.

Objective:To study the effects of poly adenosine diphosphate ribose polymerase (PARP) inhibitors niraparib and pamiparib on the radiosensitivity of breast cancer cell lines MCF-7 and MDA-MB-436, and to explore its mechanism.Methods:MCF-7 and MDA-MB-436 cells were divided into control group, niraparib group, pamiparib group, radiation group, combination group treated with niraparib and radiation, and combination group treated with pamiparib and radiation, respectively. The effects of drugs on cell proliferation and radiosensitivity were measured by CCK-8 assay and colony formation assay, respectively. The effect of drugs combined with radiation on cell cycle and apoptosis were detected by flow cytometry. Immunofluorescence method was used to detect the changes of γ-H2AX focal number of cells. The expressions of FANCG, Bax and Bcl-2 mRNA and protein were detected by qPCR and Western blot, respectively.Results:Both niraparib and pamiparib inhibited the proliferation of breast cancer cells MCF-7 and MDA-MB-436 in a time-dose dependent manner. With the increase of irradiation dose, D0, Dq, SF2 value of MCF-7 and MDA-MB-436 cells decreased, and SER D0 and SER Dq value increased. Compared with control group, the percentages of cells in G 2/M phase were increased ( tMCF-7=41.66, 44.08, P<0.05; t436=24.69, 18.91, P<0.05), the percentage of cells in G 0/G 1 phase were decreased ( tMCF-7=8.67, 29.61, P<0.05; t436=26.39, 29.12, P<0.05), and the cell apoptosis rate was significantly increased ( tMCF-7=11.17, 11.71, P<0.05; t436=42.68, 15.89, P<0.05) in the combination group. Compared with control group, the number of γ-H2AX foci of MCF-7 cells in the radiation group and combination group treated with niraparib and radiation increased significantly at 2 h after irradiation ( t=8.89, 21.72, P<0.05). At 24 h after irradiation, the number of γ-H2AX foci basically returned to normal level in the radiation group but remained at a higher level in the combination group ( t=8.82, P<0.05). Compared with control group, the expressions of FANCG and Bcl-2 mRNA decreased ( tFANCG=14.07, P<0.05; tBcl-2=29.21, P<0.05), the expression of Bax mRNA increased ( t=8.90, P<0.05), and the expression of FANCG and Bcl-2 proteins decreased ( tFANCG=7.09, P<0.05; tBcl-2=10.24, P<0.05), while the expression of Bax protein increased ( t=2.90, P<0.05) in the combination group. Conclusions:PARP inhibitors niraparib and pamiparib can increase the radiosensitivity of breast cancer MCF-7 and MDA-MB-436 cells probably through down-regulating the expression of FANCG in FA-BRCA pathway, up-regulating apoptosis-related genes and inhibiting DNA damage repair.

Objective : To investigate whether NaHS，a hydrogen sulfide donor，can improve myocardial injury in sepsis by inhibiting oxidative stress and activating the Xc －/ GPX4 signaling pathway in ferroptosis． Methods : Lipopolysacc-haride(LPS) induced H9c2 in rat cardiomyocytes to form an in vitro model of myocardial injury in sep- sis，which was divided into Control group，LPS group and LPS + NaHS group．The kits were applied to detect the changes of cardiomyocyte viability，Fe2 + ，LDH and CK-MB，determine the levels of oxidative stress indexes GSH and MDA，detect the changes of cellular ROS and mitochondrial membrane potential levels by fluorescent probes， and detect the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 by Western blot. Results: Compared with the Control group，H9c2 cell viability decreased，Fe2 + concentration increased ，GSH ，MDA and ROS levels increased，mitochondrial JC-1 monomer increased ，expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 decreased，and cell damage increased after LPS stimulation (P＜0. 05) ．Compared with the LPS group，NaHS attenuated LPS-induced H9c2 cell injury and elevated Fe2 + concentration，decreased the level of LPS-induced oxidative stress in H9c2 cells ，and increased the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 (P＜0. 05 ) ． Conclusion The mechanism by which NaHS attenuates myocardial injury in sepsis may be related to the inhibition of oxidative stress and activation of the Xc －/ GPX4 signaling pathway in fer- roptosis.

Objective To explore the method and clinical effect of radial artery pedigreed conjoined perfora-tor flap for repairing cross-joint long-shaped skin and soft tissue defects in fingers. Methods From June, 2015 to June,2017,six patients with cross-joint long-shaped skin and soft tissue defects of the fingers were treated with radial artery pedigreed conjoined flap which axis was the artery superficial line, and carried two radial artery perforators, in order to enlarge flap cut range to repair.The size of flaps ranged from 3.0 cm ×6.0 cm to 3.5 cm ×7.5 cm.The donor site was directly sutured. After operation, all patients were followed up for 3 to 8 months. All the necessary parts are observed, such as the flaps appearances, textures, the donor sites, checked the flap sensation, activity functions of the fingers. Results Six cases of flap all survived.The wounds healed well(phase I),and all patients were followed up for 3 to 8 months, with an average of 5 months. All the flaps do not obviously bloat, the textures were soft,the colors are normal,the appearances of flaps were similar to recipient sites. The donor sites healed well only with linear scars. Conclusion Using radial artery pedigreed conjoined perforator flap to repair cross-joint long-shaped skins and soft tissue defects in fingers that it not only can enlarge the cut range but also cut conveniently, the textures are close to recipient sites.Therefore,it is an ideal repair way.

Objective To investigate the predictive value of serum lipoprotein-associated phospholipase A2(Lp-PLA2) for the outcomes in patients with large atherosclerotic stroke (LAA). Methods Patients with LAA admitted to the Second People's Hospital of Lianyungang from March 2015 to January 2018 were enrolled retrospectively. The outcomes were evaluated by the modified Rankin Scale at 90 d after onset, 0-2 was defined as good outcome. Multivariate logistic regression analysis was used to identify the independent risk factors for poor outcome. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of Lp-PLA2for outcomes. Results A total of 121 patients with LAA were enrolled, including 64 males (52.9%) and 57 females (47.1%), aged 63.5 ±9.5 years; 72 (59.5%) had good outcome and 49 (40.5%) had poor outcome. The differences were statistically significant in the proportion of diabetic patients (26.4% vs.65.3%; χ2=18.110, P<0.001) and glycated hemoglobin ( 6.39% ±2.33% vs. 7.58% ±3.12%; t=1.663, P=0.041), baseline National Institutes of Health Stroke Scale (NIHSS) score (5 [3-6] vs.10[7 -14]; Z= -7.498, P< 0.001), and Lp-PLA2(194.7 ±84.3 μg/L vs.291.4 ± 82.6 μg/L; t= -5.447, P<0.001) between the good outcome group and the poor outcome group. Multivariate logistic regression analysis showed that diabetes ( odds ratio [ OR] 1.215, 95% confidence interval [CI] 1.102-1.601; P=0.046), glycosylated hemoglobin ( OR 2.275, 95% CI 1.065-4.865; P=0.037), baseline NIHSS score ( OR 2.113, 95% CI 1.585-2.734; P=0.015), and Lp-PLA2(OR 5.183, 95% CI 3.203-8.134; P<0.001) were the independent risk factors for poor outcomes in patients with LAA. ROC analysis showed that the area under the curve of Lp-PLA2predicting poor outcome was 0 .792 (95% CI 0.713-0.872); the optimal cut-off value was 260.5 μg/L, the sensitivity for predicting poor outcome was 79.6%, and the specificity was 84.7%. Conclusion The higher serum Lp-PLA2level is an independent predictive factor for poor outcome in patients with LAA. It has a higher predictive value for poor outcome.

Objective To investigate the effect of preventive antidepressants application on the prognosis of and serum brain derived neurotrophic factor(BDNF) level in acute cerebral infarction(ACI).Methods One hundred and forty-one patients with ACI were prospectively and randomly selected.Seventy-two cases in the intervention group was added with sertraline for 12 weeks on the basis of the routine therapy,while 69 cases in the control group only used the routine therapy.The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the nervous function impairment degree and daily living ability.The Hamilton Depression Rating Scale-17 was used to evaluate the emotion after stroke.The cognition function was evaluated by the Mini-Mental State Examination (MMSE).The BDNF level was detected by using the double antibody sandwich enzyme-linked immunosorbent assay.Results The NIHSS and HAMD scores after 3-month treatment were (1.77±0.58)points and (5.43±1.77)points in the intervention group,and (4.06±0.79)points and(10.27±3.78)points in the control group,which were significantly decreased compared with before treatment(P＜0.05);the BI value in the intervention group and control group were (96.24±4.58) and (77.64±6.96),which weresignificantly increased compared with before treatment (P＜0.05),and serum BDNF levels were (8.38±0.74)ng/mL and (5.72 ±0.67)ng/mL respectively,which were significantly increased compared with before treatment,moreover the change in the intervention group was more obvious than that in the control group (P＜0.05).The MMSE score had no statistical difference between the two groups (P＞0.05).The PSD occurrence rate was 10.0％ in the intervention group,which was significantly decreased compared with 53.6％ in the control group (P＜0.05).Conclusion Preventive antidepressants application in the patients with ACI can increase the serum BDNF level,improves the prognosis and is worth promotion and application.

Objective To investigate the relationship between the right-to-left shunt(RLS)detected with contrast-enhanced transcranial Doppler (c-TCD) and recurrent stroke in patients with cryptogenic stroke.Methods The consecutive patients w ith ischemic stroke w ere enrol ed. The patients w ith cryptogenic stroke w ere screened according to the TOAST criteria. They w ere divided into either a RLS positive group or a RLS negative group according to the c-TCD findings, and then they w ere fol ow ed up for a period of one year. They w ere also divided into a recurrent group and a non-recurrent group according to w hether they had recurrence or not. Results A total of 118 patients w ith cryptogenic ischemic stroke w ere enrol ed, including 46 in the RLS positive group, 72 in the RLS negative group, 10 in the recurrent group, and 108 in the non-recurrent group. There w ere no significant differences in demographic and baseline data betw een the RLS negative group and the RLS positive group. There w ere significant differences in RLS positive rate (7/10 vs.39/108; P=0.046) and proportion of patients with server RLS (2/10 vs.1/108; P=0.019) betw een the recurrent group and the non-recurrent group. Multivariate logistic regression analysis show ed that the positive RLS w as an independent predictor of recurrent stroke (odds ratio 4.896, 95% confidence interval 1.135-21.120;P=0.033). Conclusions The positive RLS may be an independent risk factor for the recurrence in patients w ith cryptogenic ischemic stroke.

Objective To examine the effect and mechanism of different targets of glucose control on liver damage in rats with sepsis .Methods The rat sepsis model was established by cecal ligation and puncture (CLP) .Forty Sprague‐Dawley rats were randomly divided into five groups (eight rats to each group):sham operation (sham group) ,sepsis (CLP group) ,glycemic control A group (glucose target 4 .6‐6 .1 mmol/L ) ,glycemic control B group (glucose target 6 .2‐8 .3 mmol/L ) and glycemic control C group (glucose target 8 .4‐10 .0 mmol/L) .The animals were sacrificed 12 hours after CLP .Venous blood was sampled for testing alanine transaminase (ALT ) , aspartate transaminase (AST ) and free fatty acid (FFA ) . Peroxisome proliferator activated receptor‐α (PPAR‐α) and liver carnitine palmitoyltransferase 1 (CPT‐1 ) protein were determined by immunohistochemistry .The pathological changes of liver tissue was observed under an optical microscope .Results The levels of ALT ,AST and FFA in venous blood and the pathological tissue injury score in sepsis groups were higher than those in sham group and all glycemic control groups (P<0 .05) .However ,the level of these markers significantly decreased in group A than those in group B or group C (P<0 .05) ,and lower in group B than those in group C (P< 0 .05) .PPARα and liver CPT‐1 expression levels were lower in sepsis group than those in sham group and all glycemic control groups except group C (P>0 .05) .The levels of PPARαand liver CPT‐1 were significantly higher in group A than in group B or group C (P<0 .05) ,and lower in group C than in group B(P<0 .05) .Conclusions The lowest target of glucose control(4 .6‐6 .1 mmol/L)shows better protective effects on liver damage in rats with sepsis ,the mechanism of which may be related to upregulation of PPARα and liver CPT‐1 expression .

Objective To investigate the dynamic changes and influencing factors of peripheral blood white blood cells (WBC), differential counts (DCs) and platelet (PLT) count in preterm infants to understand the changing characteristics of these blood parameters in preterm infants of different postnatal age, gestational age, and birth weight.Methods Totally 2 849 preterm infants admitted to the Department of Neonatology of Northwest Women's and Children's Hospital from November 30, 2011 to November 30, 2014 were retrospectively analyzed except for those diagnosed with infectious diseases, hematological system diseases, or immunologic diseases.All of the subjects were divided into seven groups based on their postnatal age, three groups based on gestational age and three groups based on birth weight, or male and female groups, respectively.Peripheral blood samples were obtained for determination of WBC, DCs and PLT.Statistical analysis was performed with oneway analysis of variance, t-test and Spearman linear correlation analysis.Results WBC, neutrophil (Ne), lymphocyte (Ly), monocyte (Mo), eosinophil (Eo), basophil (Ba) and PLT counts were significantly different among the seven groups of preterm babies of different postnatal age (F=172.00, 364.90, 34.88, 14.22, 80.82, 168.10 and 86.64, respectively, all P ＜ 0.01).WBC was found to be at the peak value within one day after birth [(18.40±6.87)× 109/L], followed by remarkable decrease in day ＞ 2-≤ 5 [(10.62±4.68)× 109/L], further gradual decrease thereafter, and then being stable in day ＞ 14-≤ 21 and ＞ 21 ≤≤ 30 [(10.54±3.09)× 109/L and (10.27 ± 3.70) × 109/L, respectively].PLT counts showed no significant change within one day after birth and in day ＞ 1-≤ 2 [(240.56± 63.54)× 109/L and (240.85 ± 71.47) × 109/L, respectively], then began to increase in day ＞ 2-≤ 5 [(249.21 ±80.55)× 109/L], peaked in day ＞ 7-≤ 14 [(339.11 ± 121.84)× 109/L], and decreased gently and became stable finally.The changing trends of Ne and Ly were cross and inverted in day ＞ 5-≤ 7.WBC, Ne, Ly, Mo, Eo, Ba and PLT counts of the preterm infants were all correlated with the postnatal age shown by Spearman linear correlation analysis (r=-0.46,-0.60, 0.18,-0.07, 0.33,-0.47 and 0.29, respectively, all P ＜ 0.01).With the increase of gestational age, WBC, Ne, Mo, and PLT counts increased, but Ly and Eo counts decreased.And all of the above showed significant difference (F=81.00, 124.49, 13.34, 18.35, 5.35 and 4.11, respectively, all P ＜ 0.05).While, the WBC, Ne, Mo, Ba and PLT counts showed positive relationship with the increase of birth weight (F=122.12, 133.09, 39.38, 13.77 and 21.24, respectively, all P ＜ 0.05).WBC, Ne and PLT counts of female infants were higher than those of male babies (t=l 6.35, 16.72 and 13.19, respectively, all P ＜ 0.05).Conclusions The peripheral WBC, DCs and PLT counts of preterm infants change dynamically with postnatal age with the remarkable variations on day ＞2-≤ 5 after birth and stable after 14 days of age.WBC, DCs and PLT counts might all be influenced by gestational age, birth weight and gender to some cxtend.

Objective To investigate the correlation between the plasma homocysteine (Hcy) level and intra/extracranial artery stenosis in patients with ischemic stroke.Methods The medical history,baseline clinical data,imaging and Hcy and other laboratory test results in patients with ischemic stroke were collected.The patients were divided into either a stenosis group or a non-stenosis group according to magnetic resonance angiography.The artery stenosis group was further redivided into an isolated intracranial stenosis group,an isolated extracranial stenosis group,and combined extracranial and intracranial stenosis group.The relationship between plasma Hcy level and intra/extracranial stenosis was analyzed.Results A total 147 patients with ischemic stroke were enrolled,including 115 patients in the stenosis group and 32 in the non-stenosis group.There were significant differences in age (t =4.577,P ＜ 0.001),the plasma levels of Hcy (t =3.65,P ＜ 0.001),C-reactive protein (t =2.06,P =0.041),low-density lipoprotein cholesterol (LDL-C) (t =1.896,P =0.046),high-density lipoprotein cholesterol (HDL-C) (t =-4.261,P ＜ 0.001),as well as the proportions of diabetes mellitus (x2 =5.772,P =0.016),hypertension (x2 =10.507,P =0.001) and smoking (x2 =12.282,P ＜ 0.001) between the stenosis group and the non-stenosis group.Multivariate logistic regression analysis showed that age ≥60 years (odds ratio [OR] 3.374,95％ confidence interval [CI] 1.351-8.426; P=0.009),Hcy ＞15 mmol/L (OR 2.274,95％ CI 1.147-8.173; P=0.025),hypertension (OR 5.782,95％ CI 2.045-16.345; P =0.001),and smoking (OR 3.514,95％ CI 1.200-10.293; P=0.002) were the independent risk factors,while HDL-C ＞ 1.0 mmol/L was an independent protective factor for intra/extracranial stenosis (OR 0.166,95％ CI 0.054-0.511; P =0.002).The stenosis group was redivided into an isolated extracranial stenosis group (n =24),an isolated intracranial stenosis group (n =61) and a combined extracranial and intracranial stenosis (n =30) according to the sites of stenosis.The comparison of the clinical data and risk factors among the three groups showed that there were significant differences in the proportions of patients with hypertension (x2 =7.024,P=0.003),as well as the plasma levels of LDL-C (F =3.276,P =0.042) and C-reactive protein (F =3.645,P =0.029).Multivariate logistic regression analysis showed that hypertension was the common independent risk factor for isolated intracranial stenosis (OR 3.795,95％ CI 1.261-11.424; P =0.018),isolated extracranial artery stenosis (OR 18.490,95％ CI 3.117-10.966; P=0.001) and combined extracranial and intracranial stenosis (OR 9.178,95％ CI2.211-38.094; P=0.002),and the increased HDL-C level was the common protective factor for isolated intracranial artery stenosis (OR 0.150,95％ CI 0.043-0.523; P =0.003),isolated extracranial artery stenosis (OR 0.078,95％ CI 0.012-0.488; P=0.006) and combined extracranial and intracranial stenosis (OR 0.089,95％ CI 0.021-0.385; P=0.001).Age was an independent risk factor for isolated intracranial stenosis (OR 6.351,95％ CI 2.277-17.717; P ＜ 0.001).The increased LDL-C level was an independent risk factor for isolated extracranial stenosis (OR 6.021,95％ CI 1.212-29.917; P =0.028).The increased Hcy level was an independent risk factor for isolated extracranial stenosis (OR 4.376,95％ CI 1.026-18.671; P-0.046) and combined extracranial and intracranial stenosis (OR 4.951,95％ CI 1.378-17.783; P =0.014).Conclusions The increased plasma Hcy level correlated with extracranial stenosis.