Study on preparation and properties of silver alloy for Mongolian medicine acupuncture.

The Mongolian medical silver needles often encounter issues of bending, fracturing, and blunting in clinical applications. Similarly, Mongolian warm needles can cause burns on patients due to inaccurate temperature control. In this study, we developed an Ag85Cu15 alloy specifically for acupuncture needles based on material preparation. By incorporating appropriate amounts of Mn and Ti elements, we were able to enhance the mechanical properties and biocompatibility of the acupuncture needles. Compared to commercially available silver needles, this alloy exhibited a significant increase in microhardness up to 210.2 Hv0.2 and an improved tensile strength of 880.2 MPa. Furthermore, we designed a thermoelectric effect-based temperature measurement model for precise control of the warm needle's temperature, enhancing the therapeutic effectiveness of the treatment.

Unlocking the potential: A novel prognostic index signature for acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive malignancy characterized by challenges in treatment, including drug resistance and frequent relapse. Recent research highlights the crucial roles of tumor microenvironment (TME) in assisting tumor cell immune escape and promoting tumor aggressiveness. This study delves into the interplay between AML and TME. Through the exploration of potential driver genes, we constructed an AML prognostic index (AMLPI). Cross-platform data and multi-dimensional internal and external validations confirmed that the AMLPI outperforms existing models in terms of areas under the receiver operating characteristic curves, concordance index values, and net benefits. High AMLPIs in AML patients were indicative of unfavorable prognostic outcomes. Immune analyses revealed that the high-AMLPI samples exhibit higher expression of HLA-family genes and immune checkpoint genes (including PD1 and CTLA4), along with lower T cell infiltration and higher macrophage infiltration. Genetic variation analyses revealed that the high-AMLPI samples associate with adverse variation events, including TP53 mutations, secondary NPM1 co-mutations, and copy number deletions. Biological interpretation indicated that ALDH2 and SPATS2L contribute significantly to AML patient survival, and their abnormal expression correlates with DNA methylation at cg12142865 and cg11912272. Drug response analyses revealed that different AMLPI samples tend to have different clinical selections, with low-AMLPI samples being more likely to benefit from immunotherapy. Finally, to facilitate broader access to our findings, a user-friendly and publicly accessible webserver was established and available at http://bioinfor.imu.edu.cn/amlpi. This server provides tools including TME-related AML driver genes mining, AMLPI construction, multi-dimensional validations, AML patients risk assessment, and figures drawing.

YKL-40 (chitinase-3-like protein 1) serum levels are associated with abdominal aortic calcification in hemodialysis patients.

BACKGROUND: Vascular calcification (VC) is highly prevalent and predicts cardiovascular mortality in dialysis patients. The mechanisms are still unclear. Inflammation is a well-known inducer of VC. YKL-40 has been suggested as a novel biomarker of inflammation and has been demonstrated to be associated with cardiovascular mortality in hemodialysis patients. This study aims to evaluate the relationship between serum YKL-40 and VC in hemodialysis (HD) patients. METHODS: A total of 109 HD patients and 31 healthy controls were enrolled in the study from September 2014 to December 2014. We evaluated the abdominal aortic calcification (AAC) score by plain X-ray films of the abdomen and measured serum YKL-40 concentrations using enzyme-linked immunosorbent assay. We also examined the relationship between YKL-40 levels and AAC scores in HD patients. RESULTS: Serum YKL-40 levels in HD patients were significantly higher than those in healthy controls [199.8 (144.8, 288.7) vs. 71.9 (52.8, 89.3) ng/ml; P < 0.001]. There was a tendency that YKL-40 levels in diabetic hemodialysis patients were higher than those in nondiabetic patients [217.8 (155.3, 335.8) vs. 192.9 (135.9, 274.4) ng/ml; P = 0.093]. A significant positive correlation was found between serum YKL-40 level and AAC score in these patients (r = 0.410, P = 0.003). Multiple regression analysis showed that Ln(YKL-40) was independently associated with AAC score in HD patients (P = 0.044). CONCLUSION: This study showed high serum YKL-40 concentrations in chronic HD patients and that YKL-40 was independently associated with increased AAC in hemodialysis patients.

Construction of HMGA2 knockout model of human papillary thyroid cancer cell line TPC-1 / 中华内分泌外科杂志

Objective:To construct a TPC-1 cell model that stably knocks out the HMGA2 by using CRISPR/Cas9 gene editing technology. Methods:Recombinant pLV[2gRNA]-EGFP:T2A:Puro- U6> {hHMGA2 [gRNA# A1]*}- U6>{hHMGA2 [gRNA#A2]*} of lentiviral plasmid vector was constructed: targeting HMGA2 Dual-gRNA sequence was designed, the synthesized Dual-gRNA fragment into pLV [2gRNA]-EGFP was cloned: T2A:Puro-U6 vector, extract a single clone for sequencing verification. the constructed recombinant plasmid vector with lentivirus was packed, and TPC-1 cells were infected, puromycin was used to obtain HMGA2 knock-out single clone, PCR and sequencing verification were performed, and real-time fluorescent quantitative qPCR was used to detect HMGA2 mRNA in cells Knockout efficiency. Results:After sequencing verification, pLV [2gRNA]-EGFP targeting HMGA2: T2A: Puro-U6>{hHMGA2 [gRNA#A1]*}-U6>{hHMGA2 [gRNA #A2]*} plasmid was successfully constructed; A single clone was picked for PCR identification and gene sequencing, TPC-1 cells were successfully obtained with HMGA2 gene completely knocked out; TPC-1 cells with HMGA2 knocked out were detected by real-time fluorescent quantitative qPCR, and they did not express HMGA2 mRNA.Conclusion:CRISPR/Cas9 gene editing technology enables us to construct a human papillary thyroid cancer cell line TPC-1 cell model with stable knockout of HMGA2.

Urotensin II Induces Mice Skeletal Muscle Atrophy Associated with Enhanced Autophagy and Inhibited Irisin Precursor (Fibronectin Type III Domain Containing 5) Expression in Chronic Renal Failure.

BACKGROUND/AIMS: Skeletal muscle atrophy is one of the main manifestations of protein energy wasting. We hypothesized that urotensin II (UII) can lead to skeletal muscle atrophy through upregulating autophagy and affecting Irisin precursor fibronectin type III domain containing 5 (FNDC5) expressions. METHODS: Three animal models (the sham operation, wild-type C57BL/6 mice with 5/6 nephrectomy, UII receptor (UT) gene knockout (UTKO) mice with 5/6 nephrectomy) were designed. Skeletal muscle weight, cross-sectional area (CSA) along with UII, FNDC5, LC3, and p62 expression were investigated. C2C12 cells were differentiated for up to 4 days into myotubes. These cells were then exposed to different UII concentrations (10-5 to 10-7 M) for 6-12 h and analyzed for the expressions of autophagic markers. These cells were also exposed to the same predetermined UII concentrations for 48-72 h and analyzed for the FNDC5 expression. Myotube diameter was measured. RESULTS: Upregulation of UII expression in skeletal muscle tissue was accompanied by reduced muscle weight and skeletal muscle CSA in the 2 posterior limbs, upregulated autophagy markers expression, and downregulated FNDC5 expression in 5/6 nephrectomy mice. The decrease of skeletal muscle weight, skeletal muscle CSA, downregulation of FNDC5 expression, and the upregulation of autophagy markers were inhibited in UTKO with 5/6 nephrectomy mice. Our in vitrostudy showed that UII could directly decrease myotube diameter, induce autophagy markers upregulation, and inhibit expression of FNDC5. When UII receptor gene was interfered by UT-specific siRNA, UII induced autophagy markers upregulation and FNDC5 downregulation were inhibited. CONCLUSION: We are the first to verify UII induces mice skeletal muscle atrophy associated with enhanced skeletal muscle autophagy and inhibited FNDC5 expression in chronic renal failure.

Lower Serum Irisin Levels Are Associated with Increased Vascular Calcification in Hemodialysis Patients.

BACKGROUND/AIMS: Vascular calcification, which involves an active cellular transformation of vascular smooth muscle cells into bone forming cells, is prevalent and predicts mortality in dialysis patients. Its mechanisms are complex and unclear. We presume that irisin, a newly identified myokine also may play roles in vascular calcification in hemodialysis patients. This study aims to evaluate serum irisin levels and establish their relation to vascular calcification and other parameters in hemodialysis patients. METHODS: A total of 150 patients on maintenance hemodialysis treatment and 38 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Serum irisin concentrations were measured by ELISA. Vascular calcification was evaluated by abdominal aortic calcification scores. RESULTS: Serum irisin concentrations were significantly lower in hemodialysis patients than in controls [52.8 (22.0, 100.0) vs. 460.8 (434.8, 483.4) ng/ml, P<0.01]. In addition, irisin was negatively correlated with the parathyroid hormone level (P=0.01). The HD patients with vascular calcification showed significantly lower serum irisin concentrations [39.0 (21.7, 86.2) vs.79.0 (39.5, 130.2) ng/mL, P<0.01]. Compared with the group without vascular calcification multivariate logistic regression analyses revealed that serum irisin, HD vintage and age were significant independent determinant factors for vascular calcification in HD patients. CONCLUSION: Our results are the first to provide a clinical evidence of the association between serum irisin and vascular calcification in HD patients. Lower irisin levels, long-term hemodialysis and old ages are independent risk factors in HD patients.

Expression of Bcl-2 and Bax proteins in hippocampus of rats with abnormal thyroid function and its relationship with cognitive Impairment / 中华内分泌外科杂志

Objective To investigate the relationship between apoptotic protein Bcl-2 and Bax in rat hippocampal neurons and cognitive dysfunction in rats with abnormal thyroid function.Methods Thirty healthy Wistar rats of 8-week-old SPF grade were randomly divided into three groups:(1) Normal control group (n=10);(2)hypothyroidism group (n=10);(3) hyperthyroidism group (n=10).All rats were sacrificed at the 4th week by heart blood sampling.The serum T3 and T4,TSH were measured.Morris water maze was used to train rats in each group for 6 days.At the end of the experiment,the hippocampus was taken from the rats,and HE staining was performed.The expression of apoptotic protein bcl-2 and Bax in rat hippocampal neurons was detected by immunohistochemistry.Results ①The escape latency of hyperthyroidism and hypothyroidism group was higher than that of the normal group at different time points (P＜0.05).In the test of the target area dwell time,the difference between the hyperthyroid group,the hypothyroid group and the normal group was statistically significant (P＜0.05).In the distance test of the target quadrant,The differences between the three groups were statistically significant (P＜0.05).In the number of passes through the target quadrant,the difference between hyperthyroidism group,hypothyroidism group and normal group was statistically significant (P＜0.05),but there is no significant difference between hyperthyroidism group and hypothyroid group (P＞0.05).②Hippocampus tissue HE staining:normal control group hippocampal neurons neatly arranged,the shape of the structure was complete and uniform,the nucleus was round or oval,nucleolus obvious,chromatin uniform level and more clear,nucleus round or oval,obviously,hyperthyroidism group,hypothyroidism group of neuronal structure loose,the number decreased,arranged disorder,deep nuclear staining,shrinkage,nucleolus disappeared,cytoplasm around the empty halo,cell spacing larger.③The positive cells expressing Bcl-2 and Bax protein in the hyperthyroidism group and the hypothyroidism group were increased compared with the normal control group (P＜0.05).Compareds with hyperthyroidism group,the expression of Bcl-2 positive cells was increased in hypothyroidism (P＜0.05).Conclusions ①The spatial learning and memory abilities of the rats with hypothyroidism and the hyperthyroid are lower than those in the normal control group.②The number of apoptotic protein positive cells in Bcl-2 and Bax neurons of hippocampus in rats with hypothyroidism and hyperthyroid increased,and the proportion of Bcl-2 and Bax was impaired,which indicates that apoptosis occurred in hippocampal neurons.This process may be one of the pathogenesis of cognitive impairment.

Irisin is Associated with Urotensin II and Protein Energy Wasting in Hemodialysis Patients.

AIMS/INTRODUCTION: Irisin is a newly identified myokine which can promote energy expenditure. Urotensin II (UII) is identified as the most potent mammalian vasoconstrictor to date. Previous studies showed that UII can aggravate insulin resistance while irisin alleviate insulin resistance. Through this study, it is our aim to elucidate if UII can induce insulin resistance and also have an association with the irisin level in hemodialysis (HD) patients. MATERIALS AND METHODS: One hundred and twenty-eight patients on maintenance hemodialysis treatment and forty healthy subjects were enrolled in this study. Blood irisin concentrations and UII concentrations were measured by ELISA and RIA respectively. The body composition was analyzed by bioelectrical impedance. RESULTS: The serum irisin levels and UII levels were both significantly lower in HD patients in comparison to that of the healthy subjects. The serum irisin levels were lower in HD patients with protein energy wasting than those of the patients without protein energy wasting. The independent determinants of circulating Ln (irisin) (the natural logarithm of irisin) were UII lean body mass and patients with protein energy wasting. CONCLUSIONS: Our results are the first to provide the clinical evidence of the association among irisin, UII, and protein energy wasting. Our results hint that UII and protein energy wasting might inhibit the release or synthesis of irisin from skeletal muscles in HD patients.

Plasma clotting factor Ⅶ research on the effects of intracerebral hemorrhage in patients with craniocerebral injury / 中国基层医药

Objective To study plasma coagulation factor Ⅶ effects of intracerebral hemorrhage in patients with craniocerebral injury.Methods 120 cases of patients with traumatic brain injury were treated,for patients admitted to hospital,the hospital after 24 hours,48 hours of live clotting enzyme activation part (APlT),peripheral venous blood specimen testing international standardization ratio (INR)and the activity of platelet and F Ⅶ were detected.According to the intracranial bleeding lesions was expanded or the emergence of a new bleeding lesions,and so on and so forth were divided into research group and the control group,43 patients in the research group,77 cases in the control group.Results The study showed that the two groups of patients with injury to the first CT time, subarachnoid hemorrhage,epidural hematoma,there were no significant difference between the indexes of subdural hematoma,patients in the study group lost 48h PPSB was (653.2 ±489.8)IU,platelet (180.7 ±63.5)mL,plasma (582.7 ±411.3)mL and red blood cells (612.3 ±490.1)mL,which were higher than those of the control group [(465.7 ±278.8)IU,(0.0 ±0.0)mL,(335.1 ±261.9)mL,(378.3 ±46.3)mL],there were statistifically significant differences between the two groups(t =2.399,2.388,2.582,3.231,P =0.020,0.022,0.010,0.001), the platelet and F Ⅶ of the research group were (101.43 ±41.85)×109 /L,(93.04 ±20.98)%,which were lower than those of the control group[(128.37 ±51.49)×109 /L,(107.67 ±20.25)%],there were statistifically significant differences between the two groups(t =2.583,2.893,P =0.010,0.004).Conclusion Lower levels of platelet activity and F Ⅶ of closely associated with intracranial hemorrhage in patients with craniocerebral injury,according to the clinical indicators to predict whether patients with intracranial hemorrhage,in order to for the treatment of patients with timely and accurate to ensure the patient's life and health.

Relation between serum thyroid stimulating hormone and papillary thyroid carcinoma in Hashimoto's thyroiditis / 中华内分泌外科杂志

Objective To investigate the effect of high serum thyroid stimulating hormone (TSH) on malignant transformation of thyroid tissue in Hashimoto's thyroiditis (HT).Methods The data of 569 patients pathologically confirmed HT admitted from Jan.2009 to Dec.2013 were retrospectively analyzed.According to with or without papillary thyroid carcinoma (PTC),patients were divided into HT group and HT complicated with PTC group.Age,gender,preoperative TSH,free thyroxine,free tri-iodothyronine,thyroidperoxidaseantibody (TPOAb),antithyroglobulinanfibody (TGAb),and tumor multifocality were investigated.Results Among the 569 patients,306 patients had HT without PTC and 263 had HT with PTC.The avaerage age of patients complicated with PTC was (45.52±10.58) years,younger than that of patients without PTC (51.63+9.50) years (P＜0.05).In HT patients with or without PTC,31％ (81/263) and 22.5％ (69/306) of patients had high TSH levels,which was significantly different (P＜0.05).Among HT patients complicated with PTC,tumor multifocality was identified in 32％(26/81) of patients with high level of TSH and in 29％(52/182) of patients with normal level of TSH.The difference had no statistical significance (P＞0.05).Conclusion High preoperative TSH level may stimulate malignant transformation of thyroid tissue in HT patients.

Irisin levels are associated with urotensin II levels in diabetic patients.

AIMS/INTRODUCTION: Irisin is a newly identified myokine that can promote energy expenditure. Previous studies showed that circulating urotensin II (UII) levels were increased in diabetes, and UII could inhibit the glucose transport in skeletal muscle in diabetic mice and aggravated insulin resistance. We presumed that irisin levels are associated with UII in diabetic patients. MATERIALS AND METHODS: A total of 71 patients with type 2 diabetes and 40 healthy subjects were recruited. Blood and urinary irisin concentrations were measured by using enzyme-linked immunosorbent assay, and UII concentrations were measured by bioelectrical impedance analysis. Every participant's body composition was analyzed by bioelectrical impedance. RESULTS: The serum irisin levels were significantly lower in diabetic patients than that of controls, whereas serum UII levels were significantly higher in diabetic patients than that in that of controls. Serum irisin levels were negatively associated with circulating UII, hemoglobin A1c and the natural logarithm transformation of urinary albumin excretion, whereas serum irisin was positively associated with estimated glomerular filtration rate, and low-density lipoprotein cholesterol and urinary irisin were positively associated with urinary UII. Furthermore, circulating irisin is positively associated with muscle mass, whereas circulating UII is negatively associated with muscle mass in diabetic patients. Hemoglobin A1c and circulating UII are independent determinants of circulating irisin by multiple regression analysis. CONCLUSIONS: The present results provide the clinical evidence of an association between irisin and UII in diabetic patients. Hemoglobin A1c and circulating UII are independent determinants of circulating irisin. Our results hint that UII and high glucose might inhibit the release of irisin from skeletal muscle in diabetic patients.

[Up-regulation of intrarenal renin-angiotensin system contributes to renal damage in high-salt induced hypertension rats].

OBJECTIVE: To test the hypothesis that in a high-salt induced hypertension in normal rats, whether the changes of intrarenal renin-agiotensin system (RAS) play a critical role in renal damage and could be reflected by urinary angiotensinogen (AGT). METHODS: In the study, 27 normotensive male Wistar-Kyoto rats were divided into control group [0.3% (mass faction) NaCl in chow, n=9, NS], high-salt diet group [8% (mass faction) NaCl in chow, n=9, HS] and high-salt diet with Losartan group [8% (mass faction) NaCl in chow and 20 mg/(kg×d) Losartan in gavages, n=9, HS+L)], and were fed for six weeks. The blood pressure was monitored and urine samples were collected every 2 weeks. AGTs in plasma, kidney and urine were measured by ELISA kits. The renal cortex expression of mRNA and protein of AGT were measured by Real-time PCR and immunohistochemistry (IHC). The renin activity and ANG II were measured by radioimmunoassay (RIA) kits. RESULTS: Compared with NS, the systolic blood pressure (SBP) [(156 ± 2) mmHg vs. (133 ± 3) mmHg, P<0.05] increased significantly at the end of the 2nd week, and the urinary protein [(14.07 ± 2.84) mg/24 h vs. (7.62 ± 3.02) mg/24 h, P<0.05] increased significantly at the end of the 6th week in HS. Compared with HS, there was no significant difference in SBP (P>0.05) but the proteinuria [(9.69 ± 2.73) mg/24 h vs. (14.07 ± 2.84) mg/24 h, P<0.01] decreased significantly in HS+L. Compared with NS, there was no significant difference in the plasma renin activity, angiotensinogen and ANG II level in HS (P>0.05), but the renal cortex renin content [(8.72 ± 1.98) ng/(mL × h) vs. (4.37 ± 1.26) ng/(mL × h), P<0.05], AGT formation [(4.02 ± 0.60) ng/mg vs. (2.59 ± 0.42) ng/mg, P<0.01], ANG II level [(313.8 ± 48.76) pmol/L vs. (188.9 ± 46.95) pmol/L, P<0.05] were increased significantly in HS, and the urinary AGT and ANG II excretion rates increased significantly (P<0.05). Compared with HS, the plasma renin activity, angiotensinogen and ANG II level were significantly increased (P<0.05), but the renal cortex renin content, AGT formation, ANG II level significantly decreased (P<0.05), and the urinary AGT and ANG II excretion rates decreased significantly in HS+L (P<0.05). The urinary AGT excretion rates were positively correlated with the AGT level in the renal cortex (P<0.05). CONCLUSION: Up-regulation of intarenal RAS may contribute to renal damage in high-salt induced hypertension rats. Urinary AGT may reflect the status of intrarenal RAS.

Genotyping and detection of virulence genes for methicillin-resistant and-sensitive Staphylococcus aureus / 中国感染与化疗杂志

Objective To elucidate the difference between methicillin-resistant Staphylococcus aureus (MRSA)and methicillin-sensitive S.aureus (MSSA)in terms of genotypes and distribution of virulence genes with the clinical strains isolated from Hohhot,and explore the relationship between the changing resistance of S.aureus and the virulence transition.Methods Pulsed field gel electrophoresis (PFGE)and multi locus sequence typing (MLST)methods were employed to do molecular typing for 30 MRSA strains and 30 MSSA strains isolated from inpatients in Hohhot,Inner Mongolia.PCR method was used to profile the distribution of virulence genes among these strains.Results PFGE typing results showed that 60 S.aureus strains were classified into 19 major types.MSSA strains belonged to 16 types,mainly types I and H.MRSA strains mainly belonged to types of K and M.Among the 20 strains with different PFGE types,MRSA strains were mainly identified as ST-239 type.but the prevalence of sec ,seg ,sei,sem,sen,seo,fnbB ,ebpS and cap 5 was higher in MSSA strains than in MRSA strains (P<0.05).Conclusions The clinical strains of S .aureus isolated from Hohhot showed diverse genotyping features.ST-239 was the major PFGE type of MRSA strains.The prevalence of virulence genes was higher in MSSA strains than in MRSA strains. Characteristic cluster is found for specific virulence genes.The results also suggest that acquisition of specific antibiotic resistance may be associated with change of specific virulence feature in S.aureus.

Effects of practice of performance appraisal and distribution motivation system at Jimenli community health service center / 中华全科医师杂志

To evaluate the reforming effects of health service performance appraisal and distribution motivation system at our center,discuss some questions during the development and application of such an evaluation system and conduct comparative analysis of the policies and data before and after management pilot separation between revenue and expenditure.The performance evaluation system and distribution mechanism were established so as to boost the working efficiency of community health services and ensure their sustained and healthy developments.

Analysis of 7 cases of simple transumbilical single-tunnel laparoscopic renal cyst decortication / 中国基层医药

Objective To investigate the clinical applicated value of simple transumbilical single-tunnel laparoscopic renal cyst decortication.Methods 7 patients with renal cysts were treated with simple single-tunnel laparoscopic renal cyst decortication.Results The operations of 7 patients were succeed.The mean operative time was 37 (28 ～ 90) min,and the mean time of pulling the drain tube out was 2 (1 ～ 4) d,and the mean int aoperative blood loss was 30 (25 ～ 80) ml,and the mean bed stay was 1.5 (1 ～ 3) d,and the mean hospital stay was 4 (3 ～ 8) d.In 7 patients,no recurrence of the cyst occurred during a follow-up of 1 ～ 6 months by color-ultrasonography,CT after operation.Conclusion The simple transumbilical single-tunnel laparoscopic renal cyst decortication has advantages of economic,minimal trauma,hairdressing,rapid recovery and better effect,therefore it maybe an ideal treatment choice for renal cysts.

Diagnosis and treatment of 50 patients with delayed traumatic intracerebral hematoma / 中国基层医药

ObjectiveTo analyze the diagnosis and treatment of patients with delayed traumatic intracranial hematoma.MethodsClinical data of 50 patients with delayed traumatic intracranial hematoma were retrospectively analyzed.According to the Glasgow Outcome criteria,the prognosis of patients recovery results were assessed.ResultsIn 50 patients after treatment,a good recovery in 29 cases,moderate disability in 11 cases,5 cases of severe disability,vegetative state survival in 3 cases,2 deaths.ConclusionDelayed traumatic head injury caused by intracranial hematoma should be early diagnozed and timely treatment can improve the prognosis of patients and improve survival.

Yohimbine protects against endotoxin-induced acute lung injury by blockade of alpha 2A adrenergic receptor in rats.

BACKGROUND: Alpha 2A adrenergic receptor (AR) is a subtype of α2 AR belonging to G protein-coupled receptors, and exerts a variety of biological effects. Recent studies have demonstrated that the α2A AR activation was closely related with inflammatory reaction. The present study aimed to investigate the influence of α2A AR antagonist, yohimbine, on the severity of endotoxin-induced acute lung injury in rats. METHODS: A total of 72 male Sprague-Dawley rats were randomly divided into three groups: control group, lipopolysaccharide (LPS) group and LPS + yohimbine group. Rats were intratracheally administrated with normal saline or LPS (300 µg), and the rats in the LPS + yohimbine group were treated with additional yohimbine (2 mg/kg, i.p) soon after LPS administration. Six, 24 and 48 hours after treatment, arterial blood gas analysis was carried out, and optical microscopy was performed to evaluate pathological changes in the lung, and lung injury score was assessed. The count of white blood cells in bronchoalveolar lavage fluid (BALF) was determined. The levels of norepinephrine, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 in BALF were measured with enzyme-linked immunosorbent assay. Immunocytochemistry was performed for the detection of α2A AR on inflammatory cells in BALF. RESULTS: When compared with the control group, the oxygenation index in the LPS group was significantly decreased, and white blood cell count, the lung histopathological scores, levels of norepinephrine and IL-6 as well as α2A AR expression on inflammatory cells in the BALF were dramatically increased at different time points, and the concentrations of TNF-α and IL-1ß were also increased except at 48 hours after LPS administration. The oxygenation index decreased while white blood cell count in BALF and the lung histopathological scores were obviously increased in the LPS + yohimbine group. The level of norepinephrine in BALF was increased at each time interval in the LPS + yohimbine group, and so did the levels of TNF-α, IL-1ß and IL-6 at 6 and 48 hours after LPS administration respectively. When compared with the LPS group, the oxygenation index, white blood cell count, the lung histopathological scores and the level of IL-6 in the LPS + yohimbine group were significantly improved at each time interval, and the concentrations of TNF-α and IL-1ß were also lower at 24 hours of LPS administration (all P < 0.05). Correlation analysis indicated the level of norepinephrine was related to the levels of TNF-α, IL-1ß and IL-6 in the BALF and the lung histopathological scores (r = 0.703, r = 0.595, r = 0.487 and r = 0.688, respectively, P < 0.001) and the intensity scores of immunoreactivity to α2A AR on inflammatory cells were also associated with the levels of TNF-α, IL-1ß and IL-6 as well as the lung histopathologial scores (r = 0.803, r = 0.978, r = 0.716 and r = 0.808, respectively, P < 0.001). CONCLUSIONS: Yohimbine can inhibit TNF-α, IL-1ß and IL-6 overproduction and relieve the severity of pulmonary inflammation induced by endotoxin, which is maybe mediated by blockade of α2A AR on inflammatory cells.

Yohimbine protects against endotoxin-induced acute lung injury by blockade of alpha 2A adrenergic receptor in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Alpha 2A adrenergic receptor (AR) is a subtype of α2 AR belonging to G protein-coupled receptors, and exerts a variety of biological effects. Recent studies have demonstrated that the α2A AR activation was closely related with inflammatory reaction. The present study aimed to investigate the influence of α2A AR antagonist, yohimbine, on the severity of endotoxin-induced acute lung injury in rats.</p><p><b>METHODS</b>A total of 72 male Sprague-Dawley rats were randomly divided into three groups: control group, lipopolysaccharide (LPS) group and LPS + yohimbine group. Rats were intratracheally administrated with normal saline or LPS (300 µg), and the rats in the LPS + yohimbine group were treated with additional yohimbine (2 mg/kg, i.p) soon after LPS administration. Six, 24 and 48 hours after treatment, arterial blood gas analysis was carried out, and optical microscopy was performed to evaluate pathological changes in the lung, and lung injury score was assessed. The count of white blood cells in bronchoalveolar lavage fluid (BALF) was determined. The levels of norepinephrine, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in BALF were measured with enzyme-linked immunosorbent assay. Immunocytochemistry was performed for the detection of α2A AR on inflammatory cells in BALF.</p><p><b>RESULTS</b>When compared with the control group, the oxygenation index in the LPS group was significantly decreased, and white blood cell count, the lung histopathological scores, levels of norepinephrine and IL-6 as well as α2A AR expression on inflammatory cells in the BALF were dramatically increased at different time points, and the concentrations of TNF-α and IL-1β were also increased except at 48 hours after LPS administration. The oxygenation index decreased while white blood cell count in BALF and the lung histopathological scores were obviously increased in the LPS + yohimbine group. The level of norepinephrine in BALF was increased at each time interval in the LPS + yohimbine group, and so did the levels of TNF-α, IL-1β and IL-6 at 6 and 48 hours after LPS administration respectively. When compared with the LPS group, the oxygenation index, white blood cell count, the lung histopathological scores and the level of IL-6 in the LPS + yohimbine group were significantly improved at each time interval, and the concentrations of TNF-α and IL-1β were also lower at 24 hours of LPS administration (all P < 0.05). Correlation analysis indicated the level of norepinephrine was related to the levels of TNF-α, IL-1β and IL-6 in the BALF and the lung histopathological scores (r = 0.703, r = 0.595, r = 0.487 and r = 0.688, respectively, P < 0.001) and the intensity scores of immunoreactivity to α2A AR on inflammatory cells were also associated with the levels of TNF-α, IL-1β and IL-6 as well as the lung histopathologial scores (r = 0.803, r = 0.978, r = 0.716 and r = 0.808, respectively, P < 0.001).</p><p><b>CONCLUSIONS</b>Yohimbine can inhibit TNF-α, IL-1β and IL-6 overproduction and relieve the severity of pulmonary inflammation induced by endotoxin, which is maybe mediated by blockade of α2A AR on inflammatory cells.</p>