Objective To investigate the protective role of losartan,an angiotensin Ⅱ receptor(AT1 type)blocker,in the mechanical ventilation-induced lung injury(VILI).Methods Forty Sprague-Dawley rats weighing 300-350 g were randomly divided into the following four experimental groups(10 rats in each group):control group(group A),normal tidal volume venti-lation group(group B),large tidal volume mechanical ventilation group(group C),large tidal volume mechanical ventilation plus Losartan pretreatment group(group D).The pulmonary tissues were removed for pathological examination and detection of NF-κB activity,and the lung lavage fluid was collected for analysis of white blood cell count,total protein concentration and the level of MIP-2,after the rats were sacrificed.Results The pathology of lung tissues was normal in groups A and B.There was obvi-ous inflammatory damage in lung tissues in group C.The pathological inj uries of lung tissue were significantly reduced in group D compared with group C.The NF-κB activity and the level of p65 were significantly higher in group C than in groups A and B (P<0.01);they were significantly reduced in group D compared with group C(P<0.05).Total protein concentration,the MIP-2 level and the white blood cell count were significantly higher in group C than in groups A and B(P<0.01).They were significantly reduced in group D compared with group C(P<0.05 or 0.01).Conclusion Losartan,a selective inhibitor of sub-type AT1 receptors for angiotensin Ⅱ,can relieve VILI by inhibiting the activity of NF-κB.

Objective To investigate the effects of angiotensin Ⅱ on nuclear transcription factor-кB(NF-кB)and interleukin-8(A549 cells),and to explore the underlying mechanisms of ventilator-induced lung injure. MethodA549 cells were maintained in Dulbecco' s modified Eagle's culture medium at 37℃ with 5 ％ CO2 incubator. The cells were randomly (random number) divided into 4 groups (n =24 in each). The group A was control group. The group B,C and D had A549 cells co-incubated with Angiotensin Ⅱ 10-6 mmol/L (final concentration) for 1 h,2 h and 4 h, respectively. The samples of cell culture supematant,total cellular RNA and nuclear proteins were collected or extracted after culture of cells. The II-8 contents in cell culture supernatant were detected with enzyme linked immunosorbent assay(FLISA) .The expressions of IL-8 mRNA were measured by reverse ttanscription-polymerase chain reaction (RT-PCR).The NF-κB activities were assayed with electrophoretic mobility shift assay (EMSA). The levels of NF-κB p65 subunit were detected with Western blot. The overall differences were compared by using analysis of variance(ANOVA). Differences between two groups were assessed by q tests. ResultsThe levels of IL-8 content in cell culture supematant in groups A, B, C and D were (29.59+8.36) pg/mL,(135.35 + 28.93) pg/mL,(357.12+ 57.21) pg/mL,and (1732.13+ 261.73) pg/mL,respectively(group A vs. group B, P ＜0.01; group B vs group C, P ＜0.01;group C vs. group D, P ＜ 0.01 ) The overall differences between gtoups were statistically significant ( F =58.41,P ＜ 0.05). The expressions of IL-8 mRNA in groups A, B, C and D were (0.13±0.03)Au·nm,(0.49+0.08) Au·mm,(0.71 ±0.10) Au·mm and (0.88±0.11) Au·mm,respectively (group A vs. group B, P ＜0.01; group B vs. group C, P ＜ 0.01; group C vs. group D, P ＜ 0.05. The overall differences between groups were statistically significant (F = 19.08, P ＜ 0.05). The NF-κB activities in groups A, B, C and D were (70.37±6.57) Au·mm,(139.76± 11.72) Au·mm,(198.90± 18.95)Au·mm and (388.73±26.27) Au·mm, respectively (group A vs. group B, P ＜0.01,group B vs. groupC, P ＜0.05; group C vs. group D, P ＜ 0.01 ). The overall differences between groups were statistically significant ( F = 23.15, P ＜ 0.05). The levels of NF-κB p65 subunit in groups A, B＜ C and D were (33.05±6.23) Au·mm, (73.97 ± 5.34) Au·mm,(168.72± 8.40)Au·mm and (254.63 + 12.2) Au·mm, respectively (group A vs. group B, P ＜0.01; group B vs. group C, P ＜0.01; group C vs. group D, P ＜0.01). The overall differences between groups were statistically significant (F = 16.33,P ＜ 0.05). Conclusions The Ang Ⅱ can significantly activate the NF-κB system and up-regulate the expression of IL-8 in human lung adenocarcinoma cell line, which cause neutrophil infiltration and activation. This effect is time-dependent and induces acute lung injure, playing an important role in the underlying mechanisms of ventilator-induced lung injure.

Objective To study the effect of synthesized peptide S247 on the activation of p38MAPK of ventilator- induced lung injury.Methods Thirty healthy male SD rats were divided into group A,group B,group C,n 10.All rats were performed with mechanical ventilation,group A with tidal volume(V_T)8 ml/kg,breathing rate(p)80/min;group B with tidal volume(V_T)40 ml/kg,breathing rate(p)=80/min;group C with tidal volume(V_T)40 ml/kg,breathing rate(p)80/min.The rats in group C were intraperitoneally injected with synthesized peptide S247(100 mg/kg)once a day for a week.The time of ventilation in all groups was two hours.Rats were sacrificed after the experiment was finished. The lung lavage liquid and lung tissue were collected and stored with correct methods.The measured indexes included lung pathology change,total protein,WBC,MPO and MIP-2.The expression of p38 and p-p38 were measured by Western Blot in lung tissue.Results Compared with group A,total protein,WBC,MPO,MIP-2 and p-p38 significantly increased in group B;compared with group B,total protein,WBC,MPO,MIP-2 and p-p38 significandy decreased in group C. Conclusion Synthesized peptide S247 significantly inhibited the activation of p38 and relieved the degree of ventilator induced lung injury.

Objective To investigate the effects of erythropoietin (EPO) pretreatment on the acute lung injury induced by lipopolysaccharide (LPS) in rats and the underlying mechanism. Methods Thirty-two male SD rats weighing 180-220 g were randomly divided into 4 groups (n=8 each): group Ⅰ control (C);group Ⅱ EPO;group Ⅲ LPS and group Ⅳ EPO + LPS. EPO 3 000 U/kg was given IP in group Ⅱ , LPS 6 mg/kg was given iv in group Ⅲ . In group Ⅳ EPO 3 000 U/kg was given IP at 30 rain before iv LPS 6 mg/kg, The animals were killed at 4 h after LPS administration. Lung tissue specimens were obtained for microscopic examination. Wet/dry ratio (W/D), myeloperoxidase (MPO) activity, malondialdehyde (MDA) and nitric oxide (NO) content in lung tissue were determined. The expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine (NT) in lung tissue was determined by Western blot. Results W/D ratio, MPO activity, MDA and NO content were significantly increased and iNOS and NT expression was significantly up-regulated in LPS group as compared with control group. EPO pretreatment significantly attenuated the LPS-induced changes in group EPO + LPS. Conclusion EPO pretreatment can ameliorate the acute lung injury induced by LPS by down-regulating iNOS expression and reducing NO production.

Objective To investigate the effect of amiloride pretreatment on the acute lung injury (ALI)induced by lipopolysaccharide (LPS) in rats. Methods Thirty-two pathogen-free male SD rats weighing 200-250 g were randomly divided into 4 groups (n = 8 each); group Ⅰ received iv normal saline (group C); group Ⅱ ALI received iv LPS 6 mg/kg (group ALI); group Ⅲ received iv amiloride 10 mg/kg (group A) and group Ⅳ received amiloride 10 mg/kg iv 30 min before iv LPS ( group AL). The animals were killed by exsanguination at 6 h after iv LPS infusion. The lungs were immediately removed. Microscopic examination of lung tissue was performed. The left lung was lavaged. The total protein (TP), TNF-α and macrophage inflammatory protein-2 (MIP-2)concentrations in broncho-alveolar lavage fluid (BALF) were measured. The W/D weight ratio and the myeloperoxidase (MPO) activity and expression of Na-H exchanger-1 ( NHE1 ), p38MAPK and extracellular signal-regulated kinase (ERK) in lung tissue were determined. Results LPS significantly increased ALI score (0 = slightest, 4 = severest), W/D lung weight ratio, TP, TNF-α and MIP-2 concentrations in BALF and MPO activity and the expression of NHE1, p38MAPK and ERK in the lung as compared with. control group. Amiloride pretreatment significantly attenuated LPS-induced changes except p38MAPK expression. Conclusion Pretreatment with amiloride can attenuate LPS-induced ALI by inhibition of ERK activation.

Objective:To explore the clinical characteristics, diagnosis and treatment of acute leukemia patients during pregnancy.Methods:The clinical data of 16 cases with acute leukemia during pregnancy from January 2009 to December 2018 in the First Affiliated Hospital of USTC were retrospectively analyzed. The diagnosis and treatment regimens, pregnancy outcome, the early fetus and survival status of patients were also analyzed.Results:All 16 leukemia cases were confirmedly diagnosed and classified by bone marrow puncture, including 13 cases of acute myeloid leukemia (5 cases of non-acute promyelocytic leukemia and 8 cases of acute promyelocytic leukemia) and 3 cases of acute lymphoblastic leukemia. At the time of confirmed diagnosis, 6 patients were in first trimester, 6 cases in second trimester and 4 cases in late trimester. As for pregnancy outcome, 1 patient had natural birthing, 5 patients underwent cesarean operation, 9 patients underwent artificial abortion and 1 patient had spontaneous abortion. Chemotherapy was performed in 15 patients during pregnancy, 11 patients received chemotherapy for treatment of primary disease after pregnancy, 3 patients died during the treatment. During the follow-up of 13 cases, 8 patients survived and 5 patients lost follow-up.Conclusions:Early diagnosis of acute leukemia during pregnancy is very important. Bone marrow puncture should be performed timely to make clear diagnosis when blood routine result is abnormal during antenatal care. Multidisciplinary consultation should be initiated in time, and the best treatment plan should be worked out to guard against serious complications during pregnancy.

The 2010 and 2017 editions of the European LeukemiaNet (ELN) guideline for the diagnosis and treatment of acute myeloid leukemia (AML) have been widely used in clinical practice. With further understanding of the molecular biological mechanisms of AML and tremendous progress in the application of clinically targeted drugs, the 2022 edition ELN AML guidelines were recently published online in the Blood. The article interprets the updated key points of the guideline.

Cardiomyocyte hypertrophy is a major cause of morbidity and mortality worldwide. The aim of this study is to determine the effects of sodium tanshinone IIA sulfonate (STS) on cardiomyocyte hypertrophy induced by angiotensin II (Ang II) in vivo and in vitro. In long-term treatment, adult Wistar rats were infused with Ang II for three weeks via osmotic mini-pumps and some of them were given intragastrically of STS. Left ventricle was isolated; the ratio of left ventricular weight to body weight and systolic blood pressure (SBP) were determined and heart morphometry was assessed after hematoxylin and eosin staining. Results indicated STS inhibited Ang II-induced increases in myocyte diameter and decreased the LVW/BW ratio independent of decreasing systolic blood pressure. In vitro, treatment of cultured cardiomyocytes with STS inhibited Ang II-induced increase in cell size, protein synthesis, ANP expression, activation of extracellular signal-regulated kinase (ERK) and ERK kinase (MEK). Then we reexamined the mechanism of STS-induced anti-hypertrophic effects. Results revealed MEK inhibitor U0126 (20 microM) markedly enhanced STS-induced depressions in [3H]leucine incorporation and ANP expression. In conclusion, MEK/ERK pathway plays a significant role in the anti-hypertrophic effects of STS.
Rats, Wistar ; Rats ; Phenanthrenes/chemistry/*pharmacology ; Myocytes, Cardiac/*drug effects/enzymology/pathology ; Molecular Structure ; Mitogen-Activated Protein Kinase Kinases/*metabolism ; MAP Kinase Signaling System/*drug effects ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; Enzyme Activation/drug effects ; Cardiomegaly/chemically induced/enzymology/*metabolism/pathology ; Animals ; Angiotensin II/*antagonists & inhibitors/pharmacology

Objective:To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT.Methods:Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results:The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions:The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.