Novel STING-targeted PET radiotracer for alert and therapeutic evaluation of acute lung injury

Acute lung injury (ALI), as a common clinical emergency, is pulmonary edema and diffuse lung infiltration caused by inflammation. The lack of non-invasive alert strategy, resulting in failure to carry out preventive treatment, means high mortality and poor prognosis. Stimulator of interferon genes (STING) is a key molecular biomarker of innate immunity in response to inflammation, but there is still a lack of STING-targeted strategy. In this study, a novel STING-targeted PET tracer, [18F]FBTA, was labeled with high radiochemical yield (79.7 ± 4.3%) and molar activity (32.5 ± 2.9 GBq/μmol). We confirmed that [18F]FBTA has a strong STING binding affinity (Kd = 26.86 ± 6.79 nmol/L) and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug therapy. Our STING-targeted strategy also reveals that [18F]FBTA can trace ALI before reaching the computed tomography (CT) diagnostic criteria, and demonstrates its better specificity and distribution than [18F]fluorodeoxyglucose ([18F]FDG).

Cellular and molecular mechanisms of Notch signal in pulmonary microvascular endothelial cells after acute lung injury

Abstract This study focused on the effect and mechanism of Notch signal on pulmonary microvascular endothelial cells (PMVECs) following acute lung injury. PMVECs were cultured in vitro and randomly divided into eight groups. Grouping was based on whether cells were co-cultured with T cells (splenic CD4+T cells were isolated using MACS microbeads) and the level of Notch expression: Normal group and Normal+T cells group, Model group and Model+T cells group, Notch low-expression group and Notch low-expression+T cells group, and Notch overexpression group and Notch overexpression+T cells group. Except for the Normal group and Normal+T cells group, all other groups were treated with 500 μL lipopolysaccharide (1 μg/mL). The expression of VE-cadherin and Zo-1 protein in the Model group (with or without T cells) was lower than that in the normal group (with or without T cells), their expression in the Notch low-expression group (with or without T cells) was significantly increased, and their expression in the Notch overexpression group (with or without T cells) was significantly decreased. Compared with the normal+T cells group, the number of Treg cells in the Notch low-expression+T cells group decreased significantly (P<0.01). The number of Th17 cells in the Notch overexpression+T cells group was higher than that in the Model+T cells group (P<0.01), while the number of Treg cells decreased (P<0.01). Our results demonstrated that activated Notch signal can down-regulate the expression of the tight junction proteins VE-Cadherin and Zo-1 in PMVECs and affect Th17/Treg immune imbalance. Autophagy was discovered to be involved in this process.

The prevalence of chronic diseases and associated influencing factors among residents in Ali, Tibet in 2021 / 西安交通大学学报(医学版)

【Objective】 To assess the prevalence of chronic diseases and associated influencing factors among residents in Ali so as to provide reference for local prevention and control of chronic diseases. 【Methods】 Stratified cluster random sampling was used to investigate the prevalence of chronic diseases and their influencing factors among permanent residents over 18 years of age in Aili. 【Results】 Totally 606 subjects were included, with a prevalence of chronic diseases of 39.93% and the highest prevalence of rheumatoid arthritis of 14.03%. The prevalence of chronic diseases was significantly different among ethnicity, age, education, occupation, personnel category, family living standard, amateur physical exercise, fuel type and self-rated health (P<0.05). Logistic regression showed that the risk of chronic diseases among the residents aged 50 years and above was 2.656 (95% CI: 1.439-4.901) times higher than that of residents under 30 years; the risk of chronic diseases among the residents with elementary school education and below was 3.528 (95% CI: 1.519-8.197) times higher than that of residents with college education and above; housework personnel could reduce the risk of chronic diseases (OR=0.365, 95% CI: 0.161-0.828); residents with poor self-rated health had 5.814 (95% CI: 3.243-10.423) times higher risk of chronic diseases than those with good self-rated health; and those with a weight gain of more than 2.5 kg in the past year could increase the risk of chronic diseases (OR=2.029, 95% CI: 1.226-3.358). 【Conclusion】 The prevalence of chronic diseases is high in residents of Ali. Attention should be paid to the elderly population with poor self-rated health and tendency of weight gain. Personalized behavioral lifestyle health education is helpful in preventing the occurrence of chronic diseases.

Clearance effect of regulation of serine/threonine protein kinase-1 signaling pathway by insulin on pulmonary edema in mice with acute lung injury / 中国生物制品学杂志

@#Objective To investigate the mechanism of insulin alleviating pulmonary edema in mice with acute lung injury(ALI) by serine/threonine protein kinase-1(SGK1).Methods 32 male adult C3H/HeN mice were randomly divided into control group(only pumped with the same amount of normal saline as the treatment group),ALI group(continuously pumped with the same amount of normal saline as the treatment group after modeling),treatment group [continuously pumped with 0.1 U/(kg·h) of insulin through jugular vein after establishing ALI model] and SGK1 siRNA group[continuously pumped with 0.1 U/(kg·h) of insulin and given SGK1 siRNA(75 μg SGK1 siRNA diluted in 100 μL saline) simultaneously after establishing ALI model] with 8 mice in each group.After 8 h,the mice were killed for arterial blood gas analysis(1 h after establishment of the model) and the changes of plasma glucose levels were detected(0,1,4and 8 h);The bronchoalveolar lavage fluid(BALF) was collected to detect the content of total protein,and the alveolar epithelial permeability and lung water content were measured;The pathological changes of lung tissue and apoptosis of lung epithelial cells were observed;The protein expressions of alveolar epithelial sodium channel(ENaC) and α_1-Na~+,K~+-ATPase and the phosphorylation level of SGK1 were determined by Western blot.Results There was no significant difference in plasma glucose level of ALI and treatment group at 0,1,4 and 8 h after insulin infusion(t=1.330 0,0.986 0,0.565 7 and 0.724 3,P=0.204 7,0.340 7,0.580 6 and 0.480 8,respectively).Compared with ALI group,the partial pressure of oxygen in arterial blood in treatment group increased significantly(t=6.026,P <0.000 1),while the BALF protein content,alveolar epithelial permeability,lung water content and lung epithelial cells apoptosis decreased significantly(t=7.39,5.286,5.651 and 3.312,P <0.000 1,=0.000 4,=0.000 2 and=0.007 8,respectively),and the expression of α-ENaC and α_1-Na~+,K~+-ATPase and the phosphorylation level of SGK1 in lung tissue significantly increased(t=26,18.67 and 8.547,P <0.000 1,<0.000 1 and=0.000 1,respectively);Compared with the treatment group,the BALF protein content,alveolar epithelial permeability,lung water content and lung epithelial cells apoptosis increased significantly in SGK1 siRNA group(t=5.964,3.449,3.148 and 3.520,P=0.000 2,0.006 2,0.010 4 and0.016 9,respectively),while α-ENaC and α_1-Na~+,K~+-ATPase protein expression and SGK1 phosphorylation level decreased significantly(t=13,9.874 and 7.741,P <0.000 1,<0.000 1 and=0.001 5,respectively).Conclusion Exogenous insulin can alleviate the pulmonary edema in ALI mice,which might be mediated via up-regulation of the expressions of α-ENaC and α_1-Na~+,K~+-ATPase by SGK1.

Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome

The use of small interfering RNAs (siRNAs) has been under investigation for the treatment of several unmet medical needs, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS) wherein siRNA may be implemented to modify the expression of pro-inflammatory cytokines and chemokines at the mRNA level. The properties such as clear anatomy, accessibility, and relatively low enzyme activity make the lung a good target for local siRNA therapy. However, the translation of siRNA is restricted by the inefficient delivery of siRNA therapeutics to the target cells due to the properties of naked siRNA. Thus, this review will focus on the various delivery systems that can be used and the different barriers that need to be surmounted for the development of stable inhalable siRNA formulations for human use before siRNA therapeutics for ALI/ARDS become available in the clinic.

Extracellular vesicle activities regulating macrophage- and tissue-mediated injury and repair responses

Macrophages are typically identified as classically activated (M1) macrophages and alternatively activated (M2) macrophages, which respectively exhibit pro- and anti-inflammatory phenotypes, and the balance between these two subtypes plays a critical role in the regulation of tissue inflammation, injury, and repair processes. Recent studies indicate that tissue cells and macrophages interact

Mechanism of Tanreqing Injection in treatment of acute lung injury based on network pharmacology and molecular docking / 中国中药杂志

This study aimed to explore the mechanism of Tanreqing Injection in the treatment of acute lung injury(ALI) based on network pharmacology and molecular docking. The active components and action targets of Tanreqing Injection were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), PubChem, and SwissTargetPrediction databases, as well as available literature reports. The ALI-related targets were obtained from the GeneCards database and then mapped with Tanreqing Injection targets. Following the construction of "drug-component-potential target" network with Cytoscape 3.6.1, the potential targets were input into STRING to yield the protein-protein interaction(PPI) network, which was plotted using Cytoscape 3.6.1. Then the screened key targets were subjected to gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis based on DAVID database. The top three key targets RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB) and interleukin-6(IL6) were docked to the top three key compounds by PyMOL and AutoDock vina. A total of 58 active components of Tanreqing Injection, 597 corresponding targets and 503 common targets shared by Tanreqing Injection and ALI were fi-gured out, with the key targets AKT1, ALB and IL6 involved. GO and KEGG enrichment analysis yielded 1 445 biological processes and 148 signaling pathways, respectively. Molecular docking verified a good binding ability of the top three key targets to the top three key compounds. The analysis based on network pharmacology and molecular docking uncovered that Tanreqing Injection directly or indirectly regulated the pulmonary capillary endothelial cells and alveolar epithelial cells via anti-inflammation, thus alleviating ALI.

Multiple components of Mahuang Shengma Decoction on prevention and treatment of acute lung injury based on RAGE/NF-κB signaling pathway / 中国中药杂志

To investigate the potential molecular markers and drug-compound-target mechanism of Mahuang Shengma Decoction(MHSM) in the intervention of acute lung injury(ALI) by network pharmacology and experimental verification. Databases such as TCMSP, TCMIO, and STITCH were used to predict the possible targets of MHSM components and OMIM and Gene Cards were employed to obtain ALI targets. The common differentially expressed genes(DEGs) were therefore obtained. The network diagram of DEGs of MHSM intervention in ALI was constructed by Cytoscape 3. 8. 0, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of target genes. The ALI model was induced by abdominal injection of lipopolysaccharide(LPS) in mice. Bronchoalveolar lavage fluid(BALF) was collected for the detection of inflammatory factors. Pathological sectioning and RT-PCR experiments were performed to verify the therapeutic efficacy of MHSM on ALI. A total of 494 common targets of MHSM and ALI were obtained. Among the top 20 key active compounds of MHSM, 14 from Ephedrae Herba were found to be reacted with pivotal genes of ALI [such as tumor necrosis factor(TNF), tumor protein 53(TP53), interleukin 6(IL6), Toll-like receptor 4(TLR4), and nuclear factor-κB(NF-κB)/p65(RELA)], causing an uncontrolled inflammatory response with activated cascade amplification. Pathway analysis revealed that the mechanism of MHSM in the treatment of ALI mainly involved AGE-RAGE, cancer pathways, PI3 K-AKT signaling pathway, and NF-κB signaling pathway. The findings demonstrated that MHSM could dwindle the content of s RAGE, IL-6, and TNF-α in the BALF of ALI mice, relieve the infiltration of inflammatory cells in the lungs, inhibit alveolar wall thickening, reduce the acute inflammation-induced pulmonary congestion and hemorrhage, and counteract transcriptional activities of Ager-RAGE and NF-κB p65. MHSM could also synergically act on the target DEGs of ALI and alleviate pulmonary pathological injury and inflammatory response, which might be achieved by inhibiting the expression of the key gene Ager-RAGE in RAGE/NF-κB signaling pathway and downstream signal NF-κB p65.

Potential of modulating fibrinolytic activity in intervention of transfusion-related acute lung injury / 中国输血杂志

Transfusion-related acute lung injury (TRALI), with clinical manifestation, diagnosis and pathological mechanism consistent with acute lung injury(ALI), belongs to a sub-category of ALI. Excessive deposition of fibrin in lung is one of the characteristic of ALI, and reversing fibrin formation is of great significance to intervene ALI. The decrease of fibrinolytic activity is one of the important causes of excessive deposition of fibrin in lung, and also the important pathological feature of TRALI. This article discusses the potential of modulating fibrinolytic activity to intervene TRALI from the perspective of regulating the effectiveness of fibrinolytic activity to intervene ALI.

HMGB1 and inflammatory cytokines in experimental acute lung injury induced in rabbits / [HMGB1 e citocinas inflamatórias em lesão pulmonar aguda experimental induzida em coelhos]

The aim of this work was to measure HMGB1, TNF-alpha, and IL-8 in bronchoalveolar lavage (BAL), serum and TLR2 and TLR4mRNA expression in lung tissue of rabbits with two grades of acute lung injury (ALI). The animals were randomly assigned to groups with severe (S) and mild/moderate (MM) ALI, induced with warm saline, and a control group. HMGB1, TNF-alpha, IL-8, TLR2mRNA and TLR4mRNA were measured after ALI induction. The results showed increased levels of IL-8, TNF-alpha, HMGB1 and TLR4mRNA in the ALI groups. HMGB1, IL-8 and TNF-alpha concentrations in BAL were higher in S compared MM. Increased TLR4mRNA was observed in S and MM versus control. The results suggest an early participation of HMGB1 in ALI together with IL-8 and TNF-alpha and association with severity. TLR4 has early expression and role in ALI pathophysiology but is not associated with severity.(AU)

O objetivo deste trabalho é determinar os níveis de HMGB1, TNF-alfa e IL-8 no lavado broncoalveolar (BAL), bem como quantificar a expressão sérica de TLR2 e TLR4 mRNA em tecido pulmonar de coelhos com dois graus de lesão pulmonar aguda (LPA). Os animais foram distribuídos aleatoriamente em grupos com LPA grave (S) e leve / moderada (MM), induzidas com solução salina morna, e um grupo controle. HMGB1, TNF-alfa, IL-8, TLR2mRNA e TLR4mRNA foram medidos após a indução de LPA e quatro horas de ventilação mecânica. Os resultados mostraram níveis aumentados de IL-8, TNF-alfa, HMGB1 e TLR4mRNA nos grupos com LPA. As concentrações de HMGB1, IL-8 e TNF-alfa no LBA foram maiores no S comparado ao MM. Aumento de TLR4mRNA foi observado em S e MM versus controle. Os resultados sugerem uma participação precoce da HMGB1 na LPA em conjunto com IL-8 e TNF-alfa e associação com a gravidade da LPA. O TLR4 foi expresso na ALI e possivelmente possui papel precoce na fisiopatologia da LPA, mas sem associação com a gravidade.(AU)

Association between Lifestyle and Academic Performance among Medical Students, Majmaah, Saudi Arabia.

A healthy lifestyle includes practices such as proper nutrition, regular exercise, adequate hours of sleep, and avoiding substance abuse. Many research projects have shown that there is a correlation between lifestyle and academic performance, while others found that lifestyle is not consistent with academic achievement. We wanted to examine the association between lifestyle and academic performance among medical students of Majmaah University, Saudi Arabia.METHODSThis is a cross-sectional study, and a survey was carried out amongst the students attending college of medicine, Majmaah University, through a well-designed pre-tested questionnaire. Data were analysed using SPSS software.RESULTSA total of 171 medical students participated in the study. Most of the participants n= 119 (69.6%) were males, and the rest n= 52 (30.4%) were females. The mean age of participants was (21.64+1.88) based on the results; most of the participants n=101 (59%) were between the 2nd and 3rd academic years. The academic performance of the students did not correlate with the lifestyle habits of the students. Lifestyle parameters tested were physical activity, dietary habits, sleeping patterns, substance abuse, and the use of social media. Academic performance was measured using the cumulative grade point average (GPA) of the student. No statistically significant difference regarding academic performance was noted among the high GPA and low GPA students in relation to their lifestyle. None of the healthy behaviours like physical activity, dietary habits, sleep patterns, and substance abuse are related to the academic performance of medical students (p>0.05).CONCLUSIONSOur study showed that there was no association between lifestyle and academic performance.

MiR-222 inhibition alleviates Staphylococcal Enterotoxin B-induced inflammatory acute lung injury by targeting Foxo3

Acute lung injury (ALI) is a common acute and severe disease in clinical practice. Staphylococcal EnterotoxinB (SEB) is a superantigen that can cause inflammatory ALI. MiR-222 has been demonstrated to be upregulatedin SEB-induced inflammatory ALI, but its exact roles and functions remain ill-defined. In this study, SEBexposure led to inflammatory ALI and high expression of miR-222 in model mice and lung infiltratingmononuclear cells, but the inflammatory response and high expression of miR-222 were restored in miR-222-/-mice. Moreover, we investigated the roles of miR-222 in vitro and observed that the concentrations ofinflammatory cytokines and the expression of miR-222 were all elevated in SEB-activated splenocytes andmiR-222 inhibition reversed the effects. Foxo3 was confirmed as a direct target of miR-222. Interestingly, SEBexposure led to a decrease of Foxo3 expression, and Foxo3 knockdown partially reversed the promotion ofFoxo3 and the inhibition of inflammatory cytokines induced by miR-222 inhibitor in SEB-activated splenocytes. Our data indicated that miR-222 inhibition could alleviate SEB-induced inflammatory ALI by directlytargeting Foxo3, shedding light on the potential therapeutic of miR-222 for SEB-induced inflammation in thelung.

Efficacy of pranoprofen combined with 0.3% hyaluronic acid sodium eye drops in the treatment of dry eye after cataract surgery / 中国基层医药

Objective@#To study the effect of pranoprofen combined with 0.3% hyaluronic acid sodium eye drops on dry eye after cataract surgery.@*Methods@#From July 2016 to June 2018, 80 patients with dry eye after cataract surgery in the Traditional Chinese Medicine Hospital of Yiwu were selected study objects, and they were randomly divided into control group and observation group by double blind random assignment method, with 40 cases in each group.The control group was treated with pranoprofen eye drops alone, while the observation group was treated with pranoprofen eye drops combined with 0.3% hyaluronic acid sodium eye drops.The lacrimal gland secretion, corneal fluorescein staining (FL) and corneal rupture time (BUT) were observed before and after treatment in the two groups.The improvement of dry eye symptoms, ocular surface signs score and life satisfaction were observed in the two groups.@*Results@#There were no statistically significant differences in lacrimal gland secretion test, FL and BUT test before treatment between the two groups (all P>0.05). The lacrimal gland secretion test, BUT and FL in the control group were (6.44±0.32)mm/5 min, (1.60±0.45), (4.31±0.23)s, respectively, which in the observation group were (9.03±0.86)mm/5 min, (0.66±0.25), (5.20±0.33)s, respectively, the differences were statistically significant(t=17.79, 11.43, 13.59, all P<0.05). In the control group, significant improvement in dry eye symptoms observed in 26 cases, slightly improved in 9 cases, no improvement in 5 cases, which in the observation group were 32 cases, 8 cases, 0 case, and there was statistically significant difference between the two groups (Z=0.342, P=0.006). Ocular surface signs analysis: before treatment, the score of the control group was (3.61±1.33)points, which of the observation group was (3.65±1.27)points, the difference was not statistically significant (P=0.051); after treatment, the score of the control group was (1.97±1.21)points, which of the observation group was (1.32±0.91)points, the difference was statistically significant (t=4.673, P=0.003). Life satisfaction score: after 1, 2 and 3 weeks of treatment, the control group was (20.62±3.17)points, (22.35±2.17)points, (29.16±3.19)points respectively, and the observation group was (23.32±2.16)points, (27.41±2.51)points, (33.11±4.15)points respectively, the differences are statistically significant between the two groups(t=6.29, 8.34, 6.31, P=0.002, 0.005, 0.013).@*Conclusion@#Pranoprofen combined with hyaluronic acid sodium eye drops has significant effect in the treatment of dry eye after cataract surgery.

Efficacy of pranoprofen combined with 0.3% hyaluronic acid sodium eye drops in the treatment of dry eye after cataract surgery / 中国基层医药

Objective To study the effect of pranoprofen combined with 0.3% hyaluronic acid sodium eye drops on dry eye after cataract surgery.Methods From July 2016 to June 2018,80 patients with dry eye after cataract surgery in the Traditional Chinese Medicine Hospital of Yiwu were selected study objects , and they were randomly divided into control group and observation group by double blind random assignment method ,with 40 cases in each group.The control group was treated with pranoprofen eye drops alone ,while the observation group was treated with pranoprofen eye drops combined with 0.3% hyaluronic acid sodium eye drops.The lacrimal gland secretion , corneal fluorescein staining ( FL) and corneal rupture time (BUT) were observed before and after treatment in the two groups.The improvement of dry eye symptoms ,ocular surface signs score and life satisfaction were observed in the two groups.Results There were no statistically significant differences in lacrimal gland secretion test ,FL and BUT test before treatment between the two groups ( all P＞0.05).The lacrimal gland secretion test ,BUT and FL in the control group were (6.44 ±0.32)mm／5 min,(1.60 ±0.45),(4.31 ±0.23)s,respectively,which in the observation group were (9.03 ±0.86)mm／5 min,(0.66 ±0.25),(5.20 ±0.33)s,respectively,the differences were statistically significant(t＝17.79,11.43,13.59,all P＜0.05).In the control group,significant improvement in dry eye symptoms observed in 26 cases,slightly improved in 9 cases,no improvement in 5 cases,which in the observation group were 32 cases,8 cases,0 case,and there was statistically significant difference between the two groups (Z＝0.342,P＝0.006).Ocular surface signs analysis :before treatment,the score of the control group was (3.61 ±1.33) points, which of the observation group was (3.65 ±1.27)points,the difference was not statistically significant (P＝0.051); after treatment,the score of the control group was (1.97 ±1.21)points,which of the observation group was (1.32 ± 0.91)points,the difference was statistically significant (t＝4.673,P＝0.003).Life satisfaction score:after 1, 2 and 3 weeks of treatment, the control group was (20.62 ±3.17) points,(22.35 ±2.17) points,(29.16 ±3.19) points respectively,and the observation group was (23.32 ±2.16) points,(27.41 ±2.51) points,(33.11 ±4.15) points respectively,the differences are statistically significant between the two groups ( t＝6.29,8.34,6.31,P＝0.002, 0.005,0.013).Conclusion Pranoprofen combined with hyaluronic acid sodium eye drops has significant effect in the treatment of dry eye after cataract surgery.

Estrés nitroxidativo pulmonar y sistémico en pacientes en ventilación mecánica con sepsis sin lesión pulmonar aguda y en pacientes en ventilación mecánica sin sepsis / Pulmonary and systemic nitroxidative stress in mechanically ventilated patients with sepsis without acute lung injury and in mechanically ventilated patients without sepsis

Propósito: Durante la sepsis y la ventilación mecánica, se genera estrés oxidativo por activación de las células pulmonares endoteliales e inflamatorias y producción de especies reactivas del oxígeno (ERO). Nuestro principal objetivo fue estudiar la producción pulmonar y sistémica de óxido nítrico (•NO) y oxidantes derivados del •NO que generan estrés nitroxidativo y su relación con la lesión pulmonar aguda (LPA) en pacientes en ventilación mecánica sépticos y no sépticos. Métodos: estudiamos 69 pacientes ventilados mecánicamente, de estos 36 pacientes con sepsis y 33 pacientes sin sepsis. Los pacientes fueron estudiados dentro de las primeras 48 horas de ingreso a unidad de cuidado intensivo (UCI). La producción de estrés nitroxidativo se comparó entre los pacientes con sepsis y los pacientes ventilados mecánicamente sin sepsis (VM). Ocho pacientes de quirófano sin enfermedad pulmonar sirvieron como grupo de control sano (GCBQ). Se analizaron nitrito más nitrato (NOx - ), 3-nitrotirosina (3-NT) y malondialdehído (MDA) en líquido de lavado bronquioloalveolar (LBA). En plasma se midió NOx - (n=69). Adicionalmente en plasma se midió 3-NT, MDA, y alfa tocoferol (α-TOH). Resultados: NO x - , 3-NT, MDA en LBA y NOx - y α-TOH en plasma fueron mayores en pacientes con sepsis que en los pacientes con VM sin sepsis (todos p <0,05). Tanto los pacientes con sepsis como VM tenían concentración de NOx - en LBA mayor que el grupo de control sano (p <0,001). En los pacientes con sepsis, los pacientes que fallecieron en la UCI tuvieron concentraciones mayores de NOx - en LBA que los sobrevivientes en la UCI, 80 (70 - 127) µM en comparación con 31 (15 - 47) µM, respectivamente, p <0,001. Los pacientes con síndrome de distress respiratorio agudo (SDRA) en el grupo sepsis tuvieron mayor concentración de NOx - en LBA. Conclusiones: Durante las fases tempranas de la sepsis y la ventilación Sepsis y Estrés Nitroxidativo Pulmonar 20 mecánica hay aumento del estrés nitroxidativo pulmonar y sistémico debido a un aumento de la producción de •NO que conduce a oxidantes secundarios derivados del •NO, los que promueven la nitración de proteínas y la peroxidación de lípidos. Esto se asocia con SDRA/LPA y aumento de la mortalidad en UCI

Purpose: During sepsis and mechanical ventilation oxidative stress is generated by endothelial and inflammatory lung cells. Our main objective was to study pulmonary and systemic •NO (nitric oxide) production and nitroxidative stress in mechanically ventilated septic patients. Methods: we study 69 mechanically ventilated patients, 36 with sepsis and 33 without sepsis within the first 48 hours of ICU admission compared with 33 mechanically ventilated patients without sepsis (MV) plus eight operating room patients without lung disease served as control healthy group (ORCG). Nitrite plus nitrate (NOx - ), 3-nitrotyrosine (3-NT) and malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) were analyzed. Additionally, we measured plasma alpha tocopherol (α-TOH), MDA, and 3-NT. Results: BALF NOx - , BALF 3-NT, BALF MDA, and plasma NOx - were higher in the Sepsis than in MV patients (all p<0.05). Both SG and MV patients had higher BALF NOx - than the healthy control group (p<0.001). Sepsis patients had higher plasma NOx - and α TOH than mechanically-ventilated patients without sepsis (all p <0,05). In the Sepsis patients, the ICU non-survivors had higher levels of BALF NOx - than ICU survivors 280(70 - 127) µM versus 31(15 - 47) µM, p< 0.001. Conclusions: We conclude that during early phases of sepsis there is an enhanced lung nitroxidative stress due to an increase of •NO production leading to secondary Sepsis y Estrés Nitroxidativo Pulmonar 21 •NO-derived oxidants, which promote protein nitration and lipid peroxidation. This is associated with ARDS /ALI and increased mortality in ICU

Study of pulmonary functions with DLco in acute respiratory distress syndrome/ acute lung injury syndrome

Background: The objective of this is to study the lung functions with DLco in ARDS/ALI survivors; to study and analyse the lung functions in different diseases causing ARDS/ ALI survivors and to analyse the effect of treatment strategies on lung functions with DLco in survivors.Methods: All patients who survived ARDS/ALI illness from January 2008 to July 2009 are selected and follow up for pulmonary function at discharge, 3 months and 6 months were performed post illness were recorded and compared.Results: In the study period, 37 cases were enrolled in the prospective cohort study, out of which 9(24.3%) were suffering from ALI according to American European Consensus definition. There was varied infections etiology causing ARDS/ ALI. Pulmonary function test at discharge were showing normal flow rates and volumes (94.6%), mild restriction in some cases (8.4%) as the patients included in the study does not have any past respiratory illness out of 37(100%) patients of ARDS/ALI discharged from Hospital 21(56.8%) had low DLco and 16 (43.2%) had normal DLco.Conclusions: Diffusion defect is found to be more common in the patients who had mixed infections than the patients who had single infection. There was no effect of steroids on the outcome of the patients in terms of diffusion defect.

Study of etiology and scoring system in acute lung injury and acute respiratory distress syndrome patients

Background: The acute respiratory distress syndrome (ARDS) is a clinical disorder characterized by injury to the alveolar epithelium and endothelial barriers of the lung, acute inflammation, and protein rich pulmonary edema leading to respiratory failure. Present study was carried out to investigate the mortality pattern of ALI/ARDS in the patients and to study the etiological factors leading to ALI/ARDS also to study the clinical pattern in patients with ALI/ARDS.Methods: All patients fulfilling the inclusion criteria as per the 1994 American European Consensus Conference on ARDS/ALI definition of ARDS/ALI were included in the study. On clinical examination the vital parameters were recorded. The respiratory system, abdominal, cardiovascular and central nervous systems were examined in detail. The severity of the illness was measured by the acute physiology and Chronic Health Evaluation (APACHE) Score, Multiple Organ Dysfunction score (MODS), lung injury score (LIS) and Sequential Organ Dysfunction Assessment (SOFA score). These scores were calculated on admission to our intensive care unit.Results: Out of the 65 patients 35 survived and 30 died. A multiple organ dysfunction Score of less than or equal to 4 was seen in 29 patients and more than 4 in 36 patient and a score of less than or equal to 4 was seen in 21 survivors and 8 dead patients, while a score of more than four was found in 14 patients who survived versus 22 patients who died. A lung injury score of less than or equal to 2 was seen in patients and more than 2 in 46 patients and a score of less than or equal to 2 was seen in 14 survivors and 5 non-survivors patients, while a score of more than 2 was found in 21 patients who survived versus 25 patients who died.Conclusions: The commonest etiological conditions leading to ALI/ARDS are pneumonia and tropical diseases including malaria, leptospirosis and dengue. The scoring systems, MODS, LIS and APACHE II are good indicators of the outcome of this condition. They are useful in tropical diseases as well.

Experimental Study on the Anti-hyperuricemia Effect of Different Extracts of Tongkat Ali / 中国药师

Objective:To study the effects of various extracts of Tongkat Ali on uric acid excretion and renal function in rats with hyperuricemia. Methods:Totally 60 male Wistar rats were equally divided into the blank group,the model group,the positive control group,chloroform group,ethyl acetate group and n-butanol group. The rats were fed with yeast extract,adenine and potassium oxonate to make the model of hyperuricemia. After the animal model was made successfully,the other groups continued to give the modeling a-gent except for the blank group,and the other groups were given the corresponding medicine except for the model group after giving the modeling agent for one hour. After the model agent was given for 14 days,the levels of uric acid(UA),urea nitrogen(UN) and cre-atinine (Cr) in serum and urine and the activity of xanthine oxidase (XOD) in serum and liver were measured. Results: Compared with those in the model group,the levels of uric acid in chloroform group and n-butanol group were significantly lower than those in the model group (P<0.05),besides,the levels of uric acid and creatinine in urine in chloroform group and n-butanol group significantly increased (P<0.05). Compared with that in the model group,the XOD activity of chloroform group and n-butanol group significantly decreased (P<0.01). Compared with those in the positive control group,the levels of UA,Cr and UN in serum and urine and the ac-tivity of XOD in serum and liver in chloroform group, ethyl acetate group and n-butanol group had no significant differences (P >0.05). The levels of UA,Cr and UN in serum and urine and the activity of XOD in serum and liver in chloroform group,ethyl acetate group and n-butanol group had no significant differences (P>0.05). Conclusion: The chloroform extract and n-butanol extract in Tongkat Ali can reduce the serum level of uric acid in rats with hyperuricemia induced by adenine, yeast extract and potassium ox-onate,and the function may be related with the activity inhibition of xanthine oxidase.

Protective Effect of Salidroside on Acute Lung Injury/Acute Respiratory Distress Syndrome in Rats / 中国药师

Objective:To investigate the protective effect of salidroside on acute lung injury or acute respiratory distress syndrome (ALI/ARDS) in rats. Methods:A total of 50 rats were randomly divided into five groups:the normal control group,the model group, salidroside high,medium and low (8.0,4.0,2.0 mg·kg-1) dose groups with 10 ones in each. ALI/ARDS model was prepared by tail vein injection of oleic acid (0.1 ml·kg-1). The administration route was intraperitoneal injection, once daily for continuous 3 days. At 24 h after the model preparation was successful,1.0 ml blood samples were collected through carotid artery for the blood gas analysis. The lung wet/dry weight ratio,arterial oxygen partial pressure and HE staining lung tissue pathology were detected and the expression of HMGB1 and KRT-14 in the blood of rats was detected after the drug was administered for 3 days. Results:The expres-sion of HMGB1 and KRT-14 in each salidroside was lower than that in the model group,and the differences were statistically significant between the medium and high dose groups and the model group(P<0.05). The dose and efficacy of salidroside were positively corre-lated,and the differences were statistically significant between the medium and high dose groups and the low dose group(P<0.05). The oxygen partial pressure of each salidroside group was higher than that of the model group, and the lung wet/dry weight ratio was lower than that of the model group,and the difference was statistically significant between the medium and high dose groups and the model group(P<0.05). The dose and efficacy of salidroside were positively correlated,and the difference was statistically significant between the medium and high dose groups and the low dose group(P<0.05). Compared with the model group,the lung pathological changes of each salidroside group were improved. Conclusion:Salidroside can reduce the expression of inflammatory factors HMGB1 and KRT-14 in blood,reduce pulmonary edema and increase oxygen partial pressure in ALI/ARDS rats, which shows obvious thera-peutic effect on ALI/ARDS.

Experimental study on the effect of sulfotanshinone sodium in lung fibrosis by oleic acid in ALI rats / 实用医学杂志

Objective To explore the effect and mechanism of sulfotanshinone sodium in lung fibrosis in ALI rats by intraperitoneal injection. Method The rats were divided into normal group,model group and sulfotan-shinone sodium group randomly.During the experiment,acute lung injury was induced by oleic acid in rats.Sulfo-tanshinone sodium group was treated by intraperitoneal injection of sulfotanshinone sodium for 14 days consecutively. The 12 rats were sacrificed at 7thand 14thday after last administration.The indexes of weight,arterial partial pres-sure of oxygen(PaO2),oxygenation index(PaO2/FiO2),lung index and wet/dry ratio,IL-1,TNF-α,PCⅢ,TGF-β1 and the lung histopathology of rats were observed. Results There was no difference in rat weight between the groups.The values of PaO2and PaO2/FiO2were increased.The lung index and wet/dry ratio,IL-1,TNF-α,PCⅢ, TGF-β1 and IQA were all reduced. The lung histopathology damage was significantly lightened.as compared with the model group. Conclusion It has treatment effect of sulfotanshinone sodium in lung fibrosis in the ALI rats, which may be related with the adjustment on inflammatory factor.