Objective To investigate the protective effects of recombinant human erythropoietin (rHuEPO) on acute lung injury (ALI) induced by lipopolysaccharide (LPS).Methods Fourty-five rats were randomly (random number) assigned to three groups,namely control group,model group,and rHuEPO group.ALI was induced by intravenous injection of LPS (6 mg/kg).The rHuEPO (5000 U/kg) was injected intravenously into rats 60 min before LPS challenge.The general status of rats was observed.Twelve hours after modeling,the rats were sacrificed and the tissue samples including lung tissue and blood were collected.PaO2,PaCO2,pH,the lung wet/dry weight ratio,plasma cytokines [interleukin (IL) IL-6 and tumor necrosis factor-alpha (TNF-α)],and inducible nitric oxide synthase (iNOS) were detected.Cytokines were assayed with ELISA method.Pathological changes of lung tissues were observed under light microscope and transmission electron microscopy.Results (1) Compared with the control group,PaO2,pH in the model group and in the rHuEPO group were significantly lower (P ＜ 0.05),and PaCO2 were significantly higher (P ＜ 0.05).Compared with the model group,PaO2,pH in the rHuEPO group were significantly higher (P ＜ 0.05),and PaCO2 were significantly lower (P ＜ 0.05).(2) Compared with the control group,the W/D weight ratio of lung tissues in the model group and the rHuEPO group was significantly higher (P ＜ 0.05).Compared with the model group,the W/D weight ratio of lung tissues in the rHuEPO group significantly lower (P ＜ 0.05).(3) The levels of TNF-o,IL-6 and iNOS in serum of rats in the control group were lower than those in the model group and the rHuEPO group (P ＜0.01).The serum levels of TNF-α,IL-6 and iNOS of rats in the rHuEPO group were significantly lower compared with the model group (P ＜ 0.01).(4) The light microscopy and the transmission electron microscopy showed the model group had histopathologic changes with acute diffuse lung injury manifested by intra-alveolar hemorrhage,exudate,inflammatory cells infiltration,Ⅰ type and Ⅱ type epithelial cell necrosis and detachment,and the pathological changes of lung tissue in the rHuEPO group were not as serious as those in the LPS group,showing only a little inflammatory cells infiltration of focal alveoli.Conclusions Recombinant human erythropoietin can inhibit the genesis of TNF-α,IL-6 and iNOS in serum,modifying the inflammatory response and providing protective effects against acute lung injury induced by sepsis.

The microenvironment of lymphoma is an important factor affecting the development of lymphoma, which is involved in regulating the recognition and immune response of lymphoma cells by the immune system. In the era of immunotherapy of lymphoma, the state of microenvironment also affects the effect of monoclonal antibodies, small molecular compounds and other immune targeting drugs on lymphoma cells. Among them, microenvironment-related immune escape is one of the key factors leading to the failure of lymphoma treatment. This article reviews some microenvironment factors such as stromal immune cell subsets, vascular proliferation, hypoxia, immune checkpoint and the recent research progress of immune escape.

Objective To explore the therapeutic effect of lipid emulsion on acute organophosphorus poisoning and its consequence of acute lung injury. Methods A total of 48 sealant - grade Sprague-Dawley (SD) rats were randomly divided into four groups A,B,C,D,namely saline control group,lipid emulsion control group,the conventional therapy group and lipid emulsion administration group. After dichlorvos (DDVP) 11 mg/kg was given by intra-peritoneal injection,if there was no loss of DDVP during the injection process,the model of poisoning was considered to be made successfully.Then the rat models in four groups were respectively treated:with normal saline (5 ml/kg) intravenous injection in group A,lipid emulsion (5ml/kg) intravenous injection in group B,atropine (5 mg/kg) and pralidoxime chloride (40 mg/kg) intramuscular injection in group C,and combined use of lipid emulsion (5 ml/kg) with atropine and pralidoxime chloride in group D after administration of DDVP by intra-peritoneal injection.The activity of cholinesterase (CHE) in blood was detected before and 0.5 h,2 h and 4 h after DDVP poisoning. The clinical manifestations,the survival of rats,the wet weight of rat' s lung and the pathological changes of the lung tissue were observed within following 24 h. The rates of survival and symptoms of rats were compared between paired groups by using the x2 test,and the mean values of biomarkers were compared paired groups by using t test. Results In groups A and B,the intensity of muscular fasciculation and salivation were more severe and appeared sooner after DDVP exposure in comparison with groups C and D leading to lower survival rates in group A and B. Compared with group C,the rate of 24 h survival was higher and the intensity of muscular fasciculation was weaker in group D ( P ＜ 0.05 ).In group A and group B,the 24-hour survival rates were 1/12 and 2/12,respectively ( P ＜ 0.05 ).The levels of CHE in blood significantly decreased after DDVP poisoning ( P ＜ 0.05 ).There was no significant difference in activity of CHE between group B and group A,and in groups C and D,the levels of CHE in blood were not significantly higher than that in the group B 0.5 h after DDVP poisoning ( P ＜ O.05 ).In groups C and D,the activity of CHE in blood was significantly higher compared with group A and B,and that in group D was higher compared with C,and that in group B was higher compared with A 2 and 4 hours after DDVP poisoning ( P ＜ 0.05 ).In groups C and D,the wet weight of rat lung was significantly lighter compared with groups A and B,and that in group D was lighter compared with C,and that in group B was lighter compared with A 24 h after DDVP poisoning P ＜ 0.05 ).The electron microscopic findings showed the combined use of lipid emulsion with atropine and pralidoxime chloride obviously lessened the lung histopathologic changes after DDVP poisoning.Conclusions The lipid emulsion combined with atropine and pralidoxime chloride can be beneficial to controlling the toxic symptoms,reduce the death rate,accelerate the resume of the activity of CHE in blood,and relieve the lung injury induced by acute organophosphorus poisoning.

Objective To discuss the effect of Montelukast (Mont) on MDA,SOD,W/D,TNF-α,IL-10 and NF-κBp65 in lung tissue of Wistar rats poisoned by paraquat (PQ) and also to observe the pathological changes of the lung tissue.Methods A total of 104 Wistar rats were divided into 3 groups in random (random number),namely PQ group (n =40),Mont group (n =40) and control group (n =24).PQ (20 mg/kg) was administered by intra-peritoneal route to rats of PQ group and Mont group and narcotics were used for 2 hours.Mont in dose of 50 mg/kg was administered intra-gastrically to rats of Mont group per day and saline instead were administered to PQ group and control group per day until they were sacrificed for experiment.Of both PQ group and Mont group,10 rats were sacrificed at each interval of 1,3,5 and 7 days respectively after modeling,whereas 6 rats of control group were sacrificed at each interval.The levels of MDA and SOD in lung tissue and W/D of lung tissue,the levels of serum TNF-α and IL-10 and the level of NF-κBp65 in lung tissue were determined.Further,the specimen of lung tissue was prepared for electron microscopy observation.Results The level of MDA in lung tissue of PQ group was (8.19 ± 0.53) nmol/mg prot,which was significantly higher than that of control group on the 7th day.The level of SOD in lung tissue of PQ group was (128.76 ± 10.18) U/mg prot,which was significantly lower than that of control group.In PQ group,the W/D of lung tissue (6.62 ±0.42),level of serum TNF-α (156.16 ± 11.13) pg/ml,level of IL-10 (43.63 ±4.44) pg/ml and level of NF-κBp65 in lung tissue (0.23 ±0.02) were significantly higher than those in control group (P ＜0.01).In Mont group on the 7th day,the level of serum TNF-α (129.99 ±13.13) pg/ml,level of serum IL-10 (34.28 ± 3.80) pg/ml and level of NF-κBp65 in lung tissue (0.20 ±0.02) were significantly lower than those in PQ group (P ＜ 0.01).In the PQ group,pathological changes of lung tissue under the light and electron microscopes were acute diffused lung injury manifested itself in hemorrhage,effusion and infiltration of inflammatory cells inside the alveolar space,and the necrosis and defluxion of Ⅰ type and Ⅱ type epithelia cells.The pathological changes in Mont group were localized with infiltration of scanty inflammatory cells,and Ⅰ type epithelia cells were intact and there was no obvious necrosis of Ⅱ type epithelia cells.Conclusions Mont has protective effects on acute lung injury caused by PQ poisoning in rats.

Objective To investigate the impact of systolic blood pressure (SBP) at admission on in-hospital outcomes in patients with ST elevated acute myocardial infarction (STEMI).Methods Data of 336 STEMI patients admitted from September 2008 to May 2011 were retrospectively analyzed.Total of 336 STEMI patients were classified into 4 groups as per the level of SBP at admission:group A (＜ 101 mmHg,n =59) ; group B (101-120 mmHg,n =109) ; group C (121-140 mmHg,n =98) and group D (＞ 140 mmHg,n =69).And clinical features,coronary angiography (CAG) findings,the strategy of treatment,complications and hospital mortality were compared among 4 groups with SPSS version 18.0 software.Results The mortality rates of the four groups were 18.64％,1.83％,4.08％,1.45％,respectively.The patients with SBP ＜ 106 mmHg were in greater risk of in-hospital mortality,Killip class ≥ 3 at admission,shock and refractory arrhythmias,and more patients in this group needed pacemaker and intraaortic balloon pump (IABP) treatment than patients in other 3 groups.While there was no significant difference in mortality rate between other three groups.Multivariate logistic regression analysis demonstrated SBP ＜ 101 mmHg (OR =6.368,P =0.002) and peak value of troponin Ⅰ (OR =3.781,P =0.008) were independent risk factors of in-hospital death in STEMI patients.Conclusions The STEMI patients with SBP ＜ 101 mmHg at admission had higher mortality rate and low SBP at admission had great prognostic value in short-term outcomes of STEMI.

Objective To investigate the protective effects of recombinant human erythropoietin (rHuEPO) on caecal ligation and puncture (CLP)-induced acute kidney injury (AKI).Methods A total of 260 healthy male Sprague-Dawley rats (250-300 g) were randomly divided into 6 groups:normal control group,sham group,CLP model group,the large dose rHuEPO (5000 U/kg)group,the middle dose rHuEPO (1000 U/kg) group,and the small dose rHuEPO (500 U/kg) group.The rat models of sepsis were established by CLP.In treatment groups,rats were treated with rHuEPO through caudalis injection after CLP surgery.Each group was divided into 2-,6-,12-,24-,36-hour subgroups with 10 rats.Rats were sacrificed and the tissue samples including kidney and blood samples were collected.The kidney function,plasma cytokines [interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)],kidney injury moleclue 1 (KIM-1) and inducible nitric oxide synthase (iNOS)were measured.Cytokines were determined by ELISA method.The expression of nuclear factor-kappaB (NF-κB) protein in kidneys were detected by immnunohistochemistry method.Pathological changes of kidney tissues were observed by light and transmission electron microscopy for cytokine content and apoptosis.Results Compared with CLP model group,renal function,the levels of TNF-α,IL-6,KIM-1 and iNOS in serum,the expression of NF-κB,significantly decresed in large dose rHuEPO group (all P ＜ 0.05).rHuEPO also lessened the histological changes in large dose group.rHuEPO did not lessen the histological changes in others.Conclusion rHuEPO can inhibit the levels of TNF-α,IL-6 and iNOS in serum,thus modify the inflammatory response and provide protective effects against acute kidney injury induced by sepsis.

Objective To investigate the protective effects of recombinant human erythropoietin (rHuEPO) on caecal ligation and puncture (CLP)-induced acute liver injury.Methods Ninety-six healthy male Sprague-Dawley rats weighing 250-300 g were randomly divided into 3 groups:normal control group (sham group,n =32),CLP model group (sepsis group,n =32) and rHuEPO treatment group (n =32).The rat model of sepsis was established by caecal ligation and puncture.In treatment group,rats were treated with rHuEPO 5000 U/kg administered through caudalis vein after CLP procedure.Continuous observation was carried out until 24 h after modeling.Of each group,8 rats were sacrificed at 2 h,6 h,12 h and 24 h,respectively,and then the liver tissue samples and blood samples were collected.Blood samples were assayed for determining the levels of serum cytokines [tumor necrosis factor-alpha (TNF-α)],and inducible nitric oxide synthase (iNOS) by using the enzyme-linked immunoadsorbentassay (ELISA) method.The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also detected.Histopathological changes of liver tissues were observed under optical and transmission electron microscopy.Results (①)The levels of ALT,AST,TNF-a,iNOS in serum of rats in control group were lower than those in model group and rHuEPO group (P ＜0.01).The levels of TNF-α,IL-6 and iNOS in serum of rats in rHuEPO group were decreased significantly compared with model group (P ＜ 0.01).(②) The optical microscopy and the transmission electron microscopy showed hepatocyte edema,liver focal necrosis,inflammatory cell infiltration in portal area and severe congestion of interlobular veins,hepatocyte karyopyknosis,mitochondrial and endoplasmic reticulum (ER) obviously decreased in sepsis group at 24 h.Hepatic injury was attenuated after employment of rHuEPO.Conclusions Recombinant human erythropoietin can inhibit the levels of ALT,AST,TNF-a,iNOS in serum,thus modifying the inflammatory response and providing protective effects against acute liver injury in the wake of infection.

objective:To investigate the clinical value of hepatic arterial resistance index (HARI) and miRNA-122a in the early diagnosis and prognosis of patients with septic shock complicated with liver injury.Methods:A total of 176 septic shock patients admitted to EICU of Cangzhou Central Hospital from December 2016 to February 2019 were selected as the research subjects. According to the occurrence of acute liver injury, they were divided into the liver injury group (86 cases) and the non-liver injury group (90 cases). Patients in the liver injury group were further divided into the mild liver injury group (20 cases), moderate liver injury group (25 cases), and severe liver injury group (41 cases) according to the degree of liver injury. Patients with septic shock complicated with liver injury were divided into the survival group (26 cases) and non-survival group (60 cases) according to the 28-day mortality. Forty healthy individuals were selected as controls. The clinical data of the subjects were collected. The HARI was determined by bedside color Doppler ultrasonography. The expressions of miRNA-122a in serum were determined by reverse transcriptase polymerase chain reaction (RT-PCR). Receiver operating characteristic (ROC) curves were used to analyze the value of HARI and serum miRNA-122a in the early diagnosis of septic shock combined with liver injury. Binary Logistic regression was used to analyze the prognostic risk factors of septic shock patients with liver injury.Results:① Compared with the control group, there was an increasing trend of HARI and serum miRNA-122a in patients with septic shock without liver injury and patients with septic shock complicated with liver injury, with statistically significant differences ( P <0.01). ROC curve analysis showed that the AUC of HARI and serum miRNA-122a for the diagnosis of septic shock complicated with liver injury were 0.872 (95% CI: 0.813, 0.919), and 0.796 (95% CI: 0.728, 0.854). When the cut-off of HARI was 0.738, its sensitivity to the diagnosis of septic shock complicated with liver injury was 77.65%, and the specificity was 83.53%; and when the cut-off value of miRNA-122a was 2.80, its sensitivity to the diagnosis of septic shock complicated with liver injury was 71.76%, and the specificity was 75.29%. When the AUC of HARI combined with miRNA-122a for the diagnosis of septic shock complicated with liver injury was 0.927 (95% CI: 0.876, 0.961), the optimal cut-off value was 0.276, and its sensitivity to the diagnosis of septic shock complicated with liver injury was 91.76%, with a specificity of 85.29%. ② There was no significant difference in HARI between the non-liver injury group and the mild liver injury group ( P>0.05), while the difference of serum miRNA-122a was statistically significant ( P <0.01). As the severity of liver injury increased, HARI and miRNA-122a expression in patients with septic shock complicated with liver injury showed an increasing trend, with statistically significant differences ( P <0.01). ③ Compared with patients with septic shock with liver injury in the survival group, the liver injury severity, APACHE II score, SOFA score, PCT, HARI and serum miRNA-122a expression levels were significantly increased in the death group, with statistically significant differences ( P <0.01). ④ Binary Logistic regression analysis showed that the severity of liver injury, APACHE II score, SOFA score, HARI and serum miRNA-122a were independent risk factors affecting the prognosis of patients with septic shock with liver injury. Conclusions:HARI combined with serum miRNA-122a test has high sensitivity and specificity in the evaluation of septic shock with liver injury, and have certain clinical value in the evaluation of prognosis of patients with septic shock with liver injury.

Objective:To investigate the pathogenesis, precaution and treatment of neonatal congenital complete heart block (CCHB) in twins.Methods:The clinical data of a case of premature twins with neonatal CCHB from the Department of Neonatology, the First Affiliated Hospital of Xinxiang Medical University were retrospectively analyzed and related literature was reviewed.Results:(1)Case review: the 37-year-old gravida had no symptoms.Fetal ultrasound cardiogram(fUCG)at 23 weeks of gestation indicated bradycardia and CCHB.Then, the mother was diagnosed with undifferentiated connective tissue disease.After treatment with human immunoglobulin, dexamethasone and hydroxychloroquine, fUCG at 31 weeks of gestation still suggested CCHB.An emergency cesarean section was performed on the diagnosis of threatened preterm labor.With weakly positive neonatal antinuclear antibody (ANA), and positive Ro60 and Ro52 autoantibodies, twins were diagnosed with CCHB by 24 hour-Holter monitors.One of the twins was discharged with CCHB (ventricular rate of 80-90 times/min) after systemic therapy, but the weight increased to 2 200 g. The other one of the twins suffered from the sudden decrease of heart rate and blood pressure and finally died of sudden cardiac arrest.(2) Literature search: two cases in Chinese and 9 cases in English were reviewed.Among them, 9 cases were sjogren syndrome type A (SSA)/Ro and sjogren syndrome type B(SSB)/La related CCHB, and 2 cases were idiopathic CCHB.Conclusions:The placental transfer of anti-SSA or anti-SSB is an important mechanism of neonatal CCHB in twins, and other factors may also be involved.Current treatments are unsatisfactory.Most patients need pacemaker implantation.Early diagnosis and prenatal management can improve the prognosis.