[Establishment and application of quality evaluation method for Xiaochaihu Granules based on calibrator samples].

With reference to the production process documented in Chinese Pharmacopoeia, this paper prepared the calibrator samples of Xiaochaihu Granules from multiple batches and established a method for fingerprint analysis and content determination that could be used to evaluate Xiaochaihu Granules available in market. Multiple batches of Chinese herbal pieces contained in Xiaochaihu Granules were collected for preparing the calibrator samples according to the process in Chinese Pharmacopoeia. Following the establishment of fingerprints for calibrator samples by UHPLC, the method for determining the contents of saikosaponin B2, saikosaponin B1, baicalin, wogonoside, baicalein, liquiritin, glycyrrhizin G2 and glycyrrhizic acid in Xiaochaihu Granules was established. The experimental results showed that the fingerprints of calibrator samples had 26 common peaks, covering the chemical compounds of main herbs Bupleuri Radix, Scutellariae Radix, Changii Radix, Glycyrrhizae Radix et Rhizoma, and Rhizoma Zingiberis Recens. The similarity of fingerprints for 47 batches of Xiaochaihu Granules from 31 companies with the calibrator sample fingerprint ranged from 0.74 to 0.99, indicating good applicability of the established fingerprint. The contents of main components baicalin, saikosaponin B2, and glycyrrhizic acid in Xiaochaihu Granules were within the ranges of 22.917-49.108 mg per bag(RSD 19%), 0.28-2.19 mg per bag(RSD 62%), and 0.897-6.541 mg per bag(RSD 41%), respectively. The quality difference in saikosaponin B2, and glycyrrhizic acid among different manufacturers was significant. The fingerprint analysis and content determination method for calibrator samples of Xiaochaihu Granules prepared according to the production process in Chinese Pharmacopoeia has been proved suitable for evaluating the quality of Xiaochaihu Granules from different manufacturers. Saikosaponin B2, glycyrrhizic acid, and liquiritin should be added as content control indicators for Xiaochaihu Granules, aiming to further improve the product quality.

[The Expression of Sphingosine-1-phosphate and Sphingosine-1-phosphate Receptor 1 in Mouse Model of Pulmonary Ischemia-Reperfusion Injury].

OBJECTIVE: To investigate the expressions of sphingosine 1-phosphate (S1P) and S1P G-protein-coupled receptor 1 (S1PR1) in pulmonary ischemia reperfusion injury (PIRI) tissues and explore their relationship. METHODS: The model of PIRI was established in vivo male C57BL/6 mice (n=8). The left pulmonary hilum was occluded for 30 min with a microvascular clamp through a left thoracotomy. Reperfusion began with removal of the clamp. Normal group (n=8) and sham group (n=8) were set as control. The hematoxylin and eosin (HE) staining of ultrastructural changes and wet-to-dry mass ratio in lung tissues were measured for judging the succeed model. The mRNA expressions of sphingosine kinase 1 (SphK1) and S1PR1 were determined by real-time PCR, and ELISA was used to detect the concentrations of S1P and S1PR1 in the lung tissues. RESULTS: The mRNA expressions of SphK1, S1PR1 and the concentrations of S1P and S1PR1 and wet-to-dry mass ratio of the lung tissues in ischemia-reperfusion mice were higher than those normal mice and sham operation mice (P<0.05). CONCLUSIONS: The increased expressions of S1P and S1PR1 in lung tissues after PIRI suggest that the S1P/S1PR1 signal pathway is involved in the pathophysiological process of PIRI, and may be a potential therapeutic target for it.

[Effect of curcumin on caspase-12 and apoptosis in pulmonary ischemia/reperfusion injury mice].

OBJECTIVE: To explore the effect of curcumin (CUR) on cycteinyl aspirate specific protease-12 (Caspase-12) and pneumocyte apoptosis in pulmonary ischemia/reperfusion (I/R) injury mice. METHODS: The in vivo unilateral in situ pulmonary I/R injury mouse model was established in C57BL/6J mice. Sixty experimental mice were randomly divided into six groups by random digit table, i. e., the sham-operation group (Sham), the I/R group, the I/R + dimethyl sulfoxide group (I/R + DMSO), the I/R + low dose CUR pre-treated group (I/R + CUR-100), the I/R + middle dose CUR pre-treated group (I/R + CUR-150), the I/R + high dose CUR pre-treated group (I/R + CUR-200), 10 in each group. Mice were euthanized and their left lungs were excised. Wet lung weight to dry lung weight (W/D) and the total lung water content (TLW) were tested. The morphological changes of the lung tissue were observed and index of quantitative evaluation for alveolar damage (IQA) detected under light microscope. The ultra-microstructure of the lung tissue was observed under electron microscope. The mRNA and protein expression levels of Caspase-12 and glucose regulated protein (GRP78) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Apoptosis index (AI) of the lung tissue was determined by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) method. RESULTS: Compared with the Sham group, expression levels of Caspase-12, GRP78 mRNA and protein all significantly increased in the I/R group (P < 0.05); W/D, TLW, IQA, and AI were all notably higher (P < 0.05, P < 0.01); the morphological and ultrastructural injury of the lung tissue were notably observed in I/R group. Compared with the I/R + DMSO group, expression levels of GRP78 mRNA and protein were increasingly higher in the I/R + CUR-100 group, the I/R + CUR-150 group, and the I/R +CUR-200 group (P < 0.05), expression levels of Caspase-12 mRNA and protein were lower (P < 0.05); W/D, TLW, IQA, and AI also decreased (P < 0.05, P < 0.01); the morphological and ultrastructural injury of the lung tissue were gradually alleviated in the I/R + CUR groups. CONCLUSION: CUR had better effect on the lung protection against I/R injury, which might be related to inhibition for pneumocyte apoptosis associated with Caspase-12 in excessive unfolded protein response (UPR).

Hepatoid adenocarcinoma of the lung: A case report.

BACKGROUND: Hepatoid adenocarcinoma of the lung (HAL) is a rare type of non-small cell lung cancer (NSCLC), histologically similar to hepatocellular carcinoma. HAL has high malignancy and poor prognosis, and a better treatment plan needs further study. CASE SUMMARY: In order to deeply understand the occurrence and development of HAL, here we report a case of HAL with extensive metastasis of alpha fetoprotein negative KRAS A146T mutation. The patient refused chemotherapy and received one course of treatment (immune checkpoint inhibitors), and died three months later due to progressive disease. CONCLUSION: HAL is a special type of NSCLC. The surgical treatment of HAL in the limited stage can achieve long-term survival, but most of them were in the advanced stage when they were found, and the prognosis was poor, which requires multidisciplinary comprehensive treatment.

Invasive fungal infections secondary to acute-on-chronic liver failure: a retrospective study.

Although the consequences of invasive fungal infections (IFIs) secondary to chronic hepatitis B infections secondary IFIs are serious, the incidence and main pathogenic factors of IFIs in acute-on-chronic liver failure (ACLF) patients remain unclear. This study included 1200 hepatitis B patients who were treated in the Department of Infectious Diseases, Shanghai Changzheng Hospital from January 2006 to January 2009. Patients with ACLF were screened according to the diagnostic guidelines for liver failure. Patients with ACLF and secondary IFI were the disease group, and patients with ACLF without secondary IFI were the controls. The incidence of IFI, mortality, and possible IFI causes in two groups were evaluated retrospectively. Sixty patients with ACLF had secondary IFI, of which 14 were confirmed cases and 46 were suspected cases. The incidence of IFI was 47.62% for ACLF patients. Logistic regression analysis showed that the level of hepatitis B viral (HBV) DNA was an important risk factor for secondary IFI in ACLF patients. Receiver operating characteristic curve analysis suggested that when the number of HBV DNA copies was higher than 3.16 × 10(3) copies ml(-1) , the possibility of secondary IFI in ACLF patients increased significantly, while white blood cell levels showed protective effects for these patients. The incidence of IFI is high in ACLF patients and high hepatitis B virus DNA levels may be an independent risk factor of secondary IFI in these patients.

Salvia miltiorrhiza-Containing Chinese Herbal Medicine Combined With GnRH Agonist for Postoperative Treatment of Endometriosis: A Systematic Review and meta-Analysis.

Background: Endometriosis is an estrogen-dependent gynecological inflammatory condition that may lead to infertility and recurrent pelvic pain. The purpose of this research was to determine the efficacy and safety of Salvia miltiorrhiza-containing Chinese herbal medicine (CHM) combined with gonadotropin-releasing hormone agonist (GnRH-a) for postoperative endometriosis management. Methods:Eight databases were systematically searched before October 2021, including PubMed, Embase, Cochrane Library, Scopus, Web of Sceince, CNKI, VIP, and Wanfang. Finally, all randomized controlled studies comparing Salvia miltiorrhiza-containing CHM paired with GnRH-a to GnRH-a alone for postoperative endometriosis management were included. Results: A total of 10 trials involving 836 patients were reported and analyzed. Compared with the control group, the Salvia miltiorrhiza-containing CHM combined with GnRH-a group showed significant superiority in decreasing endometriosis recurrence (risk ratio [RR] = 0.26; 95% confidence intervals [CI]: 0.16-0.41) and increasing the pregnancy rate ([RR] = 1.96; 95% CI: 1.58-2.44). Similarly, the effect of the Salvia miltiorrhiza-containing CHM combined with GnRH-a on CA-125 serum levels was positive (standardized mean difference [SMD] = -0.79; 95% CI: -1.11 to -0.47). Furthermore, this group showed a significant reduction in adverse effects. Conclusion: The results indicate that Salvia miltiorrhiza-containing CHM may be a viable choice for postoperative endometriosis therapy, with the potential to enhance pregnancy while decreasing recurrence and adverse effects.

Combined treatment with epigenetic agents enhances anti-tumor activity of MAGE-D4 peptide-specific T cells by upregulating the MAGE-D4 expression in glioma.

Objective: The study evaluated the efficacy of combined epigenetic drugs of decitabine (DAC), valproic acid (VPA), and trichostatin A (TSA) on immunotherapy against glioma. Methods: The expression and prognosis of MAGE-D4 in glioma were analyzed online, and the expression of MAGE-D4 and HLA-A2 in glioma induced by epigenetic drugs was detected by qRT-PCR, Western blot, and flow cytometry. The methylation status of the MAGE-D4 promoter was determined by pyrosequencing. An HLA-A2 restricted MAGE-D4 peptide was predicted and synthesized. An affinity assay and a peptide/HLA complex stability assay were performed to determine the affinity between peptide and HLA. CCK8 assay, CFSE assay, ELISA and ELISPOT were performed to detect the function of MAGE-D4 peptide-specific T cells. Flow cytometry, ELISA, and cytotoxicity assays were used to detect the cytotoxicity effect of MAGE-D4 peptide-specific T cells combined with epigenetic drugs against glioma in vitro. Finally, the glioma-loaded mouse model was applied to test the inhibitory effect of specific T cells on gliomas in vivo. Results: MAGE-D4 was highly expressed in glioma and correlated with poor prognosis. Glioma cells could be induced to express MAGE-D4 and HLA-A2 by epigenetic drugs. MAGE-D4-associated peptides were found that induce DCs to stimulate the highest T-cell activities of proliferation, IL-2 excretion, and IFN-γ secretion. MAGE-D4 peptide-specific T cells treated with TSA only or combining TSA and DAC had the most cytotoxicity effect, and its cytotoxicity effect on glioma cells decreased significantly after HLA blocking. In vivo experiments also confirmed that MAGE-D4-specific T cells inhibit TSA-treated glioma. Conclusion: MAGE-D4 is highly expressed in glioma and correlated with the prognosis of glioma. The novel MAGE-D4 peptide identified was capable of inducing MAGE-D4-specific T cells that can effectively inhibit glioma growth, and the epigenetic drug application can enhance this inhibition.

High Expression of Fibronectin 1 Predicts a Poor Prognosis in Glioblastoma.

OBJECTIVE: Glioblastoma multiforme (GBM), the most malignant intracranial neoplasm, is associated with a high mortality and recurrence rate due to the aggressive nature and heterogeneity of the tumor. Some of the molecular markers involved in the tumorigenesis of GBM are essential in prognosis, diagnosis, and treatment. Due to the limitations of therapeutic effects, this study aims to explore novel biomarkers with prognostic value and to provide new insights into therapeutic targets. METHODS: The expression profile of mRNAs in GBM was detected by RNA-sequencing, and differentially expressed genes were identified by integrating the data from RNA-seq results and the GEPIA2 database. Of the total 40 hub genes, FN1, P4HB, and PPIB showed prognostic significance based on both GEPIA2 and CGGA databases. The validation of FN1, P4HB, and PPIB expression by qPCR and correlation analysis with clinicopathological features were performed in 41 GBM tissues from our institution. RESULTS: Kaplan-Meier analysis revealed that FN1 and P4HB expressions levels were related to the overall survival (OS) of GBM patients (P<0.05). Multivariate analysis showed that FN1 overexpression (HR=9.199, P=0.002) was an independent and unfavorable prognostic factor for GBM patients. The median survival time was 8.5 months and 21 months for high and low expressions of FN1, respectively. CONCLUSION: It was suggested that FN1 could be an ideal target for prognosis and a potential therapeutic target in GBM.

Microrna-1224-5p Is a Potential Prognostic and Therapeutic Biomarker in Glioblastoma: Integrating Bioinformatics and Clinical Analyses.

OBJECTIVE: Glioblastoma (GBM) is the most common, invasive, and malignant primary brain tumor with a poor prognosis and high recurrence rate. It's known that some microRNAs (miRNAs) which are associated with tumorigenesis and progression can be considered as prognostic and therapeutic targets in tumors including GBM. This study aims to highlight the potential role of the core miRNAs in GBM and their potential use as a prognostic and therapeutic biomarker. METHODS: Differentially expressed miRNAs (DEmiRNAs) were identified in GBM by integrating miRNA-sequencing results and a GBM microarray dataset from the Gene Expression Omnibus (GEO) database through bioinformatics tools. The dysregulated miRNAs were identified by survival analysis through Chinese Glioma Genome Atlas (CGGA). Target genes of the dysregulated miRNAs were predicted on MiRWalk and miRTarBase database. TAM2.0 database, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were used to analyze the function of the dysregulated miRNAs. Subsequently, protein-protein interaction (PPI) network analysis was used to identify the top 20 hub targets of the up-regulated and down-regulated miRNAs, respectively. Then, core miRNAs in GBM were identified by constructing dysregulated miRNA-differentially expressed hub gene networks. Validation of the core miRNAs expression was detected in 41 GBM tissues compared to 8 normal brain tissues. Furthermore, the potential biomarkers were identified by clinical correlation analysis and survival analysis. RESULTS: Totally, 68 intersecting DEmiRNAs were identified, 40 of which were upregulated and the other 28 miRNAs were downregulated. Two upregulated and 4 downregulated miRNAs showed prognostic significance. Most differentially expressed hub genes were regulated by the miR-28-5p and miR-1224-5p, which were respectively upregulated and downregulated in GBM. The correlation between miR-1224-5p level and recurrence was statistically significant (P=0.011). Survival analysis showed that high miR-28-5p level and high miR-1224-5p level were both associated with better prognosis. Moreover, high miR-1224-5p level was an independent prognosis factor for GBM patients according to the cox regression analysis. CONCLUSION: MiRNA-1224-5p could be a potential target for the prognosis and treatment in GBM.

Identification and functional analyses of polymorphism haplotypes of protein phosphatase 2A-Aα gene promoter.

The serine-threonine protein phosphatase 2A (PP2A) is a heterotrimeric enzyme family that plays an essential regulatory role in cell growth, differentiation, and apoptosis. Mutations in the genes encoding PP2A-Aα/ß subunits are associated with tumorigenesis and other human diseases. To explore whether genetic variations in the promoter region of the PP2A-Aα gene (PPP2R1A) and their frequent haplotypes in the Han Chinese population have an impact on transcriptional activity, we collected DNA samples from 63 healthy Chinese donors and searched for genetic variations in the 5'-flanking promoter region of PPP2R1A (PPP2R1Ap). Haplotypes were characterized by Haploview analysis and individual subcloning. A set of molecular and functional experiments was performed using reporter genes and electrophoretic mobility shifting assay (EMSA). Seven genetic variations were identified within the promoter locus (2038bp) of PPP2R1A. Linkage disequilibrium (LD) patterns and haplotype profiles were analyzed using the identified genetic variants. Using serially truncated human PPP2R1A promoter luciferase constructs, we found that a 685bp (-448nt to +237nt) fragment around the transcription start site (TSS) was the core promoter region. Individual subcloning revealed the existence of six haplotypes in this proximal promoter region of PPP2R1Ap. Using luciferase reporter assays, we found that different haplotypes bearing different variant alleles exhibit distinct promoter activities. The EMSA revealed that the -241 -/G variant influences DNA-protein interactions involving the transcription factor NF-κB, which may regulate the activity of the PPP2R1A proximal promoter. Our findings suggest that functional genetic variants in the proximal promoter of the PP2A-Aα gene and their haplotypes are critical in the regulation of transcriptional activation.

A Review of miR-326 and Female Related Diseases.

MicroRNA (miRNA), a non-coding single-stranded RNA molecule with 20-23 nucleotides encoded by endogenous genes, plays an essential role in maintaining normal cell function and regulating cell proliferation, differentiation, apoptosis, autophagy, and cell metabolism. The imbalance between miRNA and genes can cause a series of diseases, including malignancies. miRNA-326 (miR-326) is extensively known for its core regulation of various biological processes. This review presents an overview of the highlights of miR-326 in female-related diseases. To understand the impact of miR-326 on female disorders, we search all published studies about miR-326 having a high incidence in female conditions, including cervical cancer, endometrial cancer, breast cancer, intrauterine adhesion, and multiple autoimmune diseases. We aim to learn about the mutual regulation mechanism between miR-326 and related genes and signaling pathways, as well as to elaborate on the value of miR-326 as a potential biomarker and therapeutic target of female diseases. Our results provide reliable evidence and new strategies for treating female tumors and autoimmune diseases.

Ischemic preconditioning attenuates pulmonary dysfunction after unilateral thigh tourniquet-induced ischemia-reperfusion.

BACKGROUND: Acute lung injury is a recognized complication of lower limb ischemia-reperfusion that has been demonstrated experimentally and in the clinical setting of aortic surgery. The application of a tourniquet can cause lower limb ischemia-reperfusion in orthopedic surgery. We studied the effect of unilateral thigh tourniquet-induced lower limb ischemia-reperfusion on pulmonary function, and the role of ischemic preconditioning in attenuating pulmonary dysfunction. METHODS: Thirty ASA I or II patients scheduled for lower extremity surgery were randomized into 2 groups: a limb ischemia-reperfusion group with tourniquet application (ischemia-reperfusion group, n = 15) and an ischemia preconditioning group (preconditioning group, n = 15), in which patients received 3 cycles of 5 minutes of ischemia, alternating with 5 minutes of reperfusion before extended use of the tourniquet. Blood gas, plasma malondialdehyde, and serum interleukin-6 (IL-6), IL-8, and IL-10 levels were measured just before tourniquet inflation, 1 hour after inflation and 2 hours, 6 hours, and 24 hours after tourniquet deflation. Arterial-alveolar oxygen tension ratio, alveolar-arterial oxygen tension difference, and respiratory index also were calculated. RESULTS: In comparison with the baseline values, arterial Po(2) and arterial-alveolar oxygen tension ratio were decreased, while alveolar-arterial oxygen tension difference and respiratory index were increased significantly 6 hours after tourniquet deflation in both groups (P < 0.01). However, these changes were less significant in the ischemic preconditioning group than those in the lower limb ischemia-reperfusion group (P < 0.01). Similarly, the increases in the malondialdehyde, IL-6, and IL-8 from 2 hours to 24 hours after release of the tourniquet in the lower limb ischemia-reperfusion group were attenuated by ischemic preconditioning. CONCLUSIONS: Pulmonary gas exchange is impaired after lower limb ischemia-reperfusion associated with the clinical use of a tourniquet for lower limb surgery. Ischemic preconditioning preceding tourniquet-induced ischemia attenuates lipid peroxidation and systemic inflammatory response and mitigates pulmonary dysfunction.

[Protective effect of Shenmai injection on lung injury induced by cardiac pulmonary bypass].

OBJECTIVE: To observe the protective effect of Shenmai Injection (SMI) on acute lung injury (ALI) induced by cardiac pulmonary bypass (CPB). METHODS: Thirty patients, scheduled to receive cardiac valve replacement by CPB for the first time, were equally randomized into 2 groups, the treated group and the control group. Cardiac valve replacement was performed under extracorporeal circulation after general anaesthesia. SMI 0.6 mL/kg was given to the treated group by adding in 250 mL physiological saline for intravenous dripping at the time between intubation under anaesthesia and CPB, while 250 mL physiological saline was given to the control group alone. Blood-gas analysis was performed with blood withdrawal from the radial artery to record PaO2, PaCO2, fraction of inspired oxygen (FiO2), by them the alveolar-arterial difference of partial oxygen pressure [P(A-a) DO2] was calculated, and the respiratory index (RI), the blood concentrations of soluble intercellular adhesion molelue-1 (sICAM-1), endothelin-1 (ET-1) and nitric oxide (NO) were measured at various time points, i.e. before anesthesia induction, 0.5 h, 2 h, 6 h and 24 h after ending CPB. RESULTS: All indices wer not significantly different between the two groups before operation (P > 0.05). After CPB, P(A-a) DO2 and RI were gradually elevated and reached the peak at 2 h after ending CPB, the increment in the treated group was lower than that in the control group (P < 0.05 or P < 0.01). Compared with the P(A-a) DO2 before anesthesia induction, P (A-a) DO2 at 0.5-24 h was statistically different (P < 0.05 or P < 0.01). Compared with the RI before anesthesia induction, RI at 2-24 h was statistically different (P < 0.05 or P < 0.01). Blood concentrations of sICAM-1 gradually raised after CPB, and reached the peak at 2 h after ending CPB, showed a higher level at 0.5-6 h after ending CPB as compared with that before anesthesia induction (P < 0.05 or P < 0.01). Blood ET-1 showed a figure of increasing as sICAM did (P < 0.05 or P < 0.01), and with a lower degree at 0.5-2 h after ending CPB in the treated group (P < 0. 01). Blood NO obviously reduced after CPB, it was lower at 0.5-24 h after ending CPB than at that before anesthesia induction (P < 0.01), and the decrement was lesser in the treated group (P < 0.05 or P < 0.01). CONCLUSION: SMI can attenuate the acute lung injury after CPB by way of inhibiting vascular endothelial cell adhesion with inflammatory cells, antagonizing lipid peroxidation, and improving the ventilation and oxygenation function of lung.

Dexmedetomidine protects against lung injury induced by limb ischemia-reperfusion via the TLR4/MyD88/NF-κB pathway.

Dexmedetomidine (DEX) can protect the lung from ischemia-reperfusion (I/R) injury, but the underlying mechanisms are not fully understood. The aims of this study were to determine whether DEX attenuates lung injury following lower extremity I/R and to investigate the related toll-like receptor 4 (TLR4) signaling pathway. Twenty-eight SD rats were divided into four groups (n = 7): Sham, I/R, I/R + DEX (25 µg/kg prior to ischemia), and I/R + DEX + Atip (250 µg/kg atipamezole before DEX treatment). Lower extremity I/R was induced by left femoral artery clamping for 3 hours and followed by 2 hours reperfusion. Quantitative alveolar damage and the wet/dry (W/D) ratio were calculated. Interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α in the bronchoalveolar lavage fluid (BALF) and serum and myeloperoxidase (MPO) in the lung were measured. The TLR4 and MyD88 mRNA expression levels were measured by RT-PCR, nuclear factor (NF)-κB, and phosphorylated NF-κB by western blot, respectively. Quantitative alveolar damage, W/D ratio, MPO, BALF and serum IL-1, IL-6, and TNF-α, and TLR4, MyD88, NF-κB, and p-NF-κB expression significantly increased in the I/R group relative to the Sham group. DEX preconditioning significantly reduced lung edema, and histological injury relative to the I/R group. Serum and BALF IL-1, IL-6, and TNF-α levels, MPO activity and TLR4, MyD88, NF-κB, and p-NF-κB expression were also significantly reduced in the I/R + DEX group compared with the I/R group. Atipamezole partially reversed all the aforementioned effects. DEX preconditioning protects the lungs against lower extremity I/R injury via α2-adrenoceptor-dependent and α2-adrenoceptor-independent mechanisms. It also suppresses the TLR4 pathway and reduces inflammation.

[Effect of Shenmai injection on expression and activity of heme oxygenase-1 in reperfusion injury after pulmonary ischemia in rabbits].

OBJECTIVE: To explore the effect of Shenmai injection the expression of heme oxygenase-1 (HO-1) in rabbits with reperfusion injury after pulmonary ischemia. METHOD: Single lung ischemia/reperfusion injury animal model was used in vivo. Twenty rabbits were randomly divided into two groups (n = 10, in each), pulmonary ischemia and reperfusion injury (PIRI) group and I-R + Shenmai injection group. The tissue slides were stained by in situ hybridization (ISH) for HO-1 to detect the expression of HO-1 in lung and to analyze the absorbance. Wet to dry ratio of lung tissue weight (W/D) and the injured alveoli rate (IAR) were measured at 180 minutes after lung reperfusion. Meanwhile the lung tissue slide was prepared for electron microscopic observation at 180 minutes after reperfusion. RESULT: HO-1 expression was upregulated in two groups in the pulmonary endothelial cells, part of pulmonary vascular smooth muscle cells, extima of vessels and epithelial cells of airway, the absorbance was 0.148 +/- 0.013, 0.158 +/- 0.012, respectively. The Shenmai injection group showed higher absorbance than those of the IRI group (P < 0.01), lower W/D and IAR values than those of the IRI group (P < 0.01) significantly and lighter abnormal changes of the lung tissue in morphologically than those of the PIRI group. CONCLUSION: Shenmai injection possesses notable protective effects on PIRI in rabbits by increasing the expression of HO-1 in lung.

Effect of two administration routes of Shenmai Injection () on pulmonary gas exchange function after tourniquet-induced ischemia-reperfusion.

OBJECTIVE: To compare the effect between nebulized and intravenous administration of Shenmai Injection () on pulmonary gas exchange function of patients following tourniquet-induced lower limb ischemia-reperfusion. METHODS: Thirty-eight patients scheduled for lower extremity surgery were randomized into three groups using the closed envelop method: Shenmai Injection was administered 30 min before tourniquet inflflation by nebulization [0.6 mL/kg in 10 mL normal saline (NS)] in the nebulization group or by intravenous drip (0.6 mL/kg dissolved in 250 mL of 10% glucose) in the intravenous drip group, and equal volume of NS was given intravenously in the NS group; 15 in each group. Arterial blood gases were analyzed, serum levels of malonaldehyde (MDA) and interleukine-6 (IL-6) and interleukine-8 (IL-8) were determined using the method of thiobarbituric acid reaction and enzyme-linked immuno sorbent assay respectively just before tourniquet inflflation (T0), and at 0.5 h (T1), 2 h (T2), 6 h (T3) after tourniquet deflflation. RESULTS: Compared with baselines at T0, MDA levels signifificantly increased at T2, T3 in the NS group and at T3 in the nebulization group, and IL-6 and IL-8 levels were signifificantly increased at T2, T3 in NS, the intravenous drip and the nebulization groups (P <0.05). Arterial pressure of oxygen (PaO2) at T3 was decreased, while alveolararterial oxygen tension showed difference (PA-aDO2) at T3 in the NS group; RI at T3 in both intravenous drip and the nebulization groups were enhanced (P <0.05). Compared with the NS group, MDA and IL-8 levels at T2, T3, IL-6 at T3 in the intravenous drip group, and IL-8 at T3 in the nebulization group were all remarkably increased (P <0.05). Additionally, MDA level at T3 in the nebulization group was higher than that in the intravenous drip group (P <0.05). CONCLUSIONS: Intravenous administration of Shenmai Injection provided a better protective effect than nebulization in mitigating pulmonary gas exchange dysfunction in patients following tourniquet-induced limb ischemia-reperfusion.

[Protective effect of ligustrazine and propofol on peri-operational liver ischemia-reperfusion injury].

OBJECTIVE: To explore the protective effect and mechanism of ligustrazine (LGT) and propofol (PRO) on peri-operational liver ischemia-reperfusion injury (HIRI). METHODS: Thirty-six patients scheduled for hepatic surgery were randomly divided into the control group, the LGT group, the PRO group and the LGT + PRO group, 9 patients in each group. Changes of superoxide dismutase (SOD), lipid peroxide (LPO), ratio of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha), alanine aminotransferase (ALT) activity, and the ultrastructure of liver tissue were dynamically observed. RESULTS: Compared with the control group, SOD activity was significantly higher, LPO concentration, TXB2/6-keto-PGF1alpha ratio and ALT value were significantly lower (P < 0.05 and P < 0.01) in the LGT group, the PRO group and the LGT + PRO group during HIRI, with the abnormal changes of hepatic ultrastructure 25 min after reperfusion significantly alleviated in the three treated group. CONCLUSION: Combination of ligustrazine and propofol shows protective effect on liver by decreasing oxygen free radical level, reducing lipid peroxidation and adjusting TXA2/PGI2 imbalance after hepatic ischemia-reperfusion in patients undergoing hepatic cancer surgery.

Effects of Angelicin on Ovalbumin (OVA)-Induced Airway Inflammation in a Mouse Model of Asthma.

Angelicin, a furocoumarin found in Psoralea corylifolia L. fruit, has been reported to have anti-inflammatory activity. The purpose of this study was to determine the protective effects of angelicin on allergic asthma induced by ovalbumin (OVA) in mice. Mice were sensitized to OVA (on days 0 and 14) and challenged with OVA three times (on days 21 to 23). Angelicin (2.5, 5, 10 mg/kg) was given intraperitoneally 1 h before OVA treatment after the initial OVA sensitization. The production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum were measured by ELISA. Lung histological changes were detected by using hematoxylin and eosin (H&E) stain. The results showed that angelicin significantly inhibited inflammatory cells infiltration into the lungs. Histological studies showed that angelicin significantly attenuated OVA-induced lung injury. Meanwhile, treatment of angelicin dose-dependently inhibited OVA-induced the production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum. Furthermore, angelicin was found to inhibit airway hyperresponsiveness and NF-kB activation. In conclusion, our results suggested that angelicin inhibited allergic airway inflammation and hyperresponsiveness by inhibiting NF-kB activation.

[Nrf2/ARE pathway mediates the reducing effect of Dexmedeto-midine on ischemia/reperfusion injury in skeletal muscle].

OBJECTIVE: To explore the role of Nrf2/ARE pathway in skeletal muscle ischemia/reperfusion(I/R) injury preconditioning by dexmedetomidine(DEX). METHODS: Twenty-eight SD rats were randomly divided into sham-operated(Sham group)、I/R group、I/R+ DEX(DEX group) and I/R+DEX +Atipamezole (Atip group). In the Atip group, Atip(250 µg/kg) and DEX(25 µg/kg) were injected together after anesthesia; In the Sham and I/R groups, the homologous saline was also injected at the same time; In the DEX group, the homologous DEX and saline were coinjected. After 30 minutes, the hind limb ischemia was induced by clamping the common femoral artery and ligaturing collateral circulation. After 3 h of ischemia, the clamp and tourniquet were removed and the rats underwent 2 h of reperfusion. We measured plasma concentrations of lactate dehydrogenase (LDH) and creatine kinase(CK). The gastrocnemius muscle was harvested and immediately stored at -80℃ for the assessment of malondialdehyde(MDA)、superoxide dismutase(SOD) and Nrf2/HO-1 protein detected by Western blot. The other section muscle was stored in triformol for immunohistochemical and HE staining. The wet/dry was also immediately detecting. RESULTS: The levels of wet/dry、MDA、LDH、CK、Nrf2 and HO-1 were higher(P<0.05) while the level of SOD was lower(P<0.05) in the I/R group than those in sham group. The levels of wet/dry、MDA、LDH、CK were significantly lower(P<0.05) yet the levels of SOD and Nrf2/HO-1 were significantly higher(P<0.05) in DEX group than those in I/R group. However, Atip reversed the effect of DEX in Atip group, each of indicators had significant changes compared with those in the DEX group(P<0.05). CONCLUSIONS: Nrf2 protein was expressed in skeletal muscle of rat and DEX could promote its level in nucleus by α-adrenergic receptor. The down-stream products of Nrf2 have the effect of antioxidant.

[Role of lipid peroxidation in hepatic ischemia-reperfusion injury and effect of L-Arginine].

OBJECTIVE: To study the role of lipid peroxidation during hepatic ischemia-reperfusion injury (HIRI) and the effects of L-Arginine (L-Arg). METHODS: The rabbits and patients who underwent elective hepatic surgery were randomly divided into two groups respectively, HIRI group and L-Arg group.Plasma malondialdehyde (MDA) and alanine aminotransferase (ALT) were measured before ischemia 45 minutes (rabbits) or 25 minutes(patients) and 45 minutes(rabbits) or 25 minutes (patients) after reperfusion. RESULTS: As compared with pre-ischemia, MDA and ALT increased during ischemia 45 minutes (or 25 minutes) in rabbits and patients, P<0.05 or P<0.01. Treatment with L-Arg could markedly reduce the elevation of mentioned biochemical parameters during hepatic ischemia. In rabbits MDA decreased on hepatic but the different were not significant (P>0.05), ALT decreased (P<0.05). In patients MDA and ALT both decreased on hepatic(both P<0.01). After reperfusion, MDA and ALT all decreased in rabbits and patients (all P<0.01). CONCLUSION: These data suggest that lipid peroxidation can play an important role in the happening and developing of HIRI. Treatment with L-Arg may attenuate ischemia-reperfusion injury by antagonizing lipid peroxidation.