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An organic-inorganic hybrid nanoprobe, namely LML-D-SBA@Eu 3+ -Gd 3+ , was constructed, with SBA-15 acting as the carrier material, and luminol and Eu 3+ acting as fluorescence channels to achieve ratiometric signals that eliminate external interference (accurate detection). Gd 3+ was used as a sensitizer to amplify the red emission of Eu 3+ (ultrasensitive detection). In TCs detection, the luminol emission at 428 nm was quenched due to the photoinduced electron transfer mechanism, and the Eu 3+ emission at 617 nm was sensitized due to the synergistic energy transfer from TCs and Gd 3+ to Eu 3+ . The fluorescence intensity at 617 and 428 nm showed ratiometric changes as indicated by notable color changes from blue to red. The detection limits for TC and OTC were 0.21 and 0.08 ng/mL, respectively. To realize a facile, rapid, and cost-effective detection, we constructed a portable intelligent sensing platform based on smartphones, and it demonstrated great potential for on-site detection of TCs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Alzheimer's disease (AD), a common degenerative disease of the central nervous system in the elderly, has become the third largest health killer after cardiovascular and cerebrovascular diseases and tumors. Based on the fact that Alzheimer's disease is a disease with multiple etiologies and complex pathology, a single target is bound to have a limited curative effect, and the synergy of multiple links and multiple targets is expected to achieve a better curative effect. The aim of this study is to investigate the brain targeting of a drug modified by chitosan, based on the new nanodrug delivery system for treating Alzheimer's disease developed by the research group., Materials and Methods: Chitosan with good biocompatibility, biosorption, and degradation products that can protect and promote the regeneration of nerve cells was selected to combine with galantamine, a natural representative cholinesterase inhibitor, to develop a new nano drug delivery system for nasal delivery of anti-Alzheimer's disease with a multi-target synergistic effect. Synchronous analysis was conducted on the blood and brain tissue drug concentrations after intravenous and nasal administration of the original drug solution and system solution. The brain targeting index (DTI) is used to evaluate the brain targeting effect of the nano-drug delivery system after intranasal administration., Results: The blood concentration of galantamine original drug solution and galantamine system solution after intravenous injection and nasal show that in the two administration methods of intravenous injection and nasal administration, under the same administration method, the time point of the system reaching the highest blood drug concentration is much higher than that of the original drug. The content of galantamine in plasma samples and tissue samples indicate that after intravenous administration and intranasal administration of the galantamine system, at the same time point, the drug concentration in brain tissue was far greater than that of the original drug of galantamine, and the duration was also longer. The concentration of drugs in brain tissue decreased gradually in the order of olfactory bulb, olfactory tract, brain, and cerebellum. In the brain tissues of the olfactory bulb, olfactory tract, cerebrum, and cerebellum, the drug concentration of the galantamine system after intravenous injection is lower than that after nasal administration., Conclusions: This study concludes that compared with the original drug solution, the nano drug delivery system has significant brain targeting for nasal administration, and intravenous injection also has brain targeting. In the olfactory bulb, olfactory tract, brain, and cerebellum, the brain targeting index at the olfactory bulb is the highest, and the targeting is the best.

The detection of residual tetracycline antibiotics (TCs) in the aquatic environment is important because of the irreversible damage of TCs to the ecosystem and human health. Considering the photostability, sensitivity, and accuracy of the detection systems, mesoporous SBA-15 silica material was an ideal support matrix for improving photostability because it can protect the optical properties of fluorescent signals. To achieve ratiometric detection (with sensitivity and accuracy), pyrene and Eu 3+ as two fluorescent signals were implemented into SBA-15, and an organic-inorganic hybrid fluorescent nanoprobe Py/EDTA-SBA-15@Eu 3+ was constructed. In the presence of TCs, the red emission of Eu 3+ in the nanoprobe was sensitized, and the fluorescence resonance energy transfer occurred from pyrene to Eu 3+ , resulting in the increased emission of Eu 3+ at 617 nm and the decreased emission of pyrene at 384 nm. By monitoring the fluorescent intensity changes at 617 and 384 nm (F 617 /F 384 ), the nanoprobe achieved the ratiometric detection of oxytetracycline (OTC) and tetracycline (TC) in the range of 0.20-80 and 0.40-80 μM, respectively, with detection limits of 0.18 nM for OTC and 5.83 nM for TC. In addition, the practical application of the nanoprobe was validated in tap water and honey samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The organic-inorganic hybrid material was prepared by embedding 2-amino-3',6'-bis(diethylamino)spiro[isoindoline-1,9'-xanthen]-3-one (RBH) onto mesoporous SBA-15 silica and coordinating it with Al 3+ (RBH-SBA-15-Al 3+ ). RBH-SBA-15-Al 3+ was used for the selective and sensitive detection of tetracycline antibiotics (TAs) in aqueous media based on the binding site-signaling unit mechanism, in which Al 3+ acted as the binding site and the fluorescence intensity at 586 nm as the response signal. The addition of TAs to RBH-SBA-15-Al 3+ suspensions resulted in the formation of RBH-SBA-15-Al 3+ -TAs conjugates, which realized the electron transfer process and turned-on fluorescence signal at 586 nm. The detection limits for tetracycline (TC), oxytetracycline, and chlortetracycline were 0.06, 0.06, and 0.03 µM, respectively. Meanwhile, the detection of TC was feasible in real samples, such as tap water and honey. In addition, RBH-SBA-15 can operate as a TRANSFER logic gate by using Al 3+ and TAs as input signals and the fluorescence intensity at 586 nm as output signal. This study proposes an efficient strategy for the selective detection of target analytes by introducing interaction sites (e.g. Al 3+ ) with target analytes in the system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with complicated pathogenesis and diverse clinical manifestations. The current recommendations of the Chinese Rheumatology Association are based on a comprehensive investigation of evidence based medicine, domestic and international guidelines for SLE, and experts' proposals, and aim to provide a more scientific and authoritative reference for the diagnosis and management of SLE. The recommendations focus on four aspects; clinical manifestations, laboratory evaluation, diagnosis and disease assessment, and disease treatment and monitoring. The goal of the recommendations is to standardize the diagnosis and treatment of SLE in China so as to improve the prognosis of SLE patients.

Objective: This study aimed to investigate the correlation of serum octapeptide cholecystokinin-8 (CCK-8), substance P (SP), and 5-hydroxytryptryptamine (5-HT) values with depression levels in patients with post-stroke depression (PSD). It also aimed to explore the potential approach for the early diagnosis of PSD., Patients and Methods: A correlation research between patients' biochemical indicators and depression levels was performed among 70 stroke patients during hospitalization from June 2021 to February 2022. The 70 stroke patients were selected and divided into post-stroke depression and non-depression groups according to the Hamilton Depression Scale (HAMD) score. The concentrations of CCK-8, SP, and 5-HT in both groups were measured, and the relationship between the values of CCK-8, SP, 5-HT and the depression levels was analyzed., Results: Among the 70 stroke survivors, 35 were in the depression group and 35 were in the non-depression group. Significant differences were observed in the concentration of CCK-8, SP, and 5-HT between the patients in the depression and non-depression group (p < 0.05). Accompanied by an increase in the depression level, the SP value gradually increased, but the CCK-8 and 5-HT values gradually decreased. Spearman correlation analysis indicated that the order of the correlation between CCK-8, 5-HT, SP, and the depression levels was CCK-8 > SP > 5-HT., Conclusions: All the CCK-8, SP and 5-HT values were correlated with the depression levels in stroke survivors. Furthermore, the correlation between CCK-8, SP, and post-stroke depression levels was higher than that of 5-HT, suggesting that the early diagnosis of PSD may be reflected more precisely through the detection of CCK-8, and SP values, thus providing potential priority for biochemical detection in the diagnosis of PSD.

Objective: To evaluate the mechanisms underlying the protective effect of Chinese herbal medicine Fructus broussonetiae (FB) in both mouse and cell models of Alzheimer's disease (AD)., Methods: APP/PS1 mice treated with FB for 2 months and vehicle-treated controls were run through the Morris water maze and object recognition test to evaluate learning and memory capacity. RNA-Seq, Western blotting, and immunofluorescence staining were also conducted to evaluate the effects of FB treatment on various signaling pathways altered in APP/PS1 mice. To further explore the mechanisms underlying FB's protective effect, PC-12 cells were treated with Aβ 25-35 in order to establish an in vitro model of AD., Results: FB-treated mice showed improved learning and memory capacity on both the Morris water maze and object recognition tests. RNA-seq of hippocampal tissue from APP/PS1 mice showed that FB had effects on multiple signaling pathways, specifically decreasing cell apoptotic signaling and increasing AKT and β-catenin signaling. Similarly, FB up-regulated both AKT and β-catenin signaling in PC-12 cells pre-treated with Aβ 25-35 , in which AKT positively regulated β-catenin signaling. Further study showed that AKT promoted β-catenin signaling via enhancing β-catenin (Ser552) phosphorylation. Moreover, AKT and β-catenin signaling inhibition both resulted in the attenuated survival of FB-treated cells, indicating the AKT/β-catenin signaling is a crucial mediator in FB promoted cell survival., Conclusions: FB exerted neuroprotective effects on hippocampal cells of APP/PS1 mice, as well as improved cell viability in an in vitro model of AD. The protective actions of FB occurred via the upregulation of AKT/β-catenin signaling.

Alpinia oxyphylla, a traditional herb, is widely used for its neuroprotective, antioxidant and memory-improving effects. However, the neuroprotective mechanisms of action of its active ingredients are unclear. In this study, we investigated the neuroprotective effects of various organic extracts of Alpinia oxyphylla on PC12 cells exposed to hydrogen peroxide-induced oxidative injury in vitro. Alpinia oxyphylla was extracted three times with 95% ethanol (representing extracts 1-3). The third 95% ethanol extract was dried and resuspended in water, and then extracted successively with petroleum ether, ethyl acetate and n-butanol (representing extracts 4-6). The cell counting kit-8 assay and microscopy were used to evaluate cell viability and observe the morphology of PC12 cells. The protective effect of the three ethanol extracts (at tested concentrations of 50, 100 and 200 µg/mL) against cytotoxicity to PC12 cells increased in a concentration-dependent manner. The ethyl acetate, petroleum ether and n-butanol extracts (each tested at 100, 150 and 200 μg/mL) had neuroprotective effects as well. The optimum effective concentration ranged from 50-200 μg/mL, and the protective effect of the ethyl acetate extract was comparatively robust. These results demonstrate that organic extracts of Alpinia oxyphylla protect PC12 cells against apoptosis induced by hydrogen peroxide. Our findings should help identify the bioactive neuroprotective components in Alpinia oxyphylla., Competing Interests: None

Objective: To review retrospectively six cases of rhino-orbital related endoscopic surgeries aided by Fusion electromagnetic system,to explore the indications and clinical value of image guided technique in endonasal endoscopic surgery. Method: Retrospective research methods were used.In this study,six cases of nasal endoscopic sinus surgery using Fusion electromagnetic system were analyzed,including 1 nasal penetrating foreign body,2 optic nerve decompressions,1 orbital apex hemangioma,1 sieve frontal sinus cyst,1 intraorbital mass biopsy.The preparation time of navigation system,the accuracy of intraoperative positioning and surgical coherence,intraoperative and postoperative complications of surgery were recorded. Result: The average preparation time was(8.13 ± 1.858)min.In the navigation,the sinus ostium,orbital cardboard,skull base,optic nerve,internal carotid artery and other important structures can be accurately located in all patients,while registrations had been accurate within 1 mm.Six patients were successfully operated by image guided technique.There was no intracranial or intraorbital complications due to intraoperation error. Conclusion: Image guided technique allows for a truely microinvasive and accurate rhino-orbital related endoscopic surgeries.It requires less preoperative preparation time,has high surgical navigation accuracy,improves the surgical coherence and safety,and reduces the surgical complicationgs.However,as an auxiliary tool,it can not replace the surgeon's anatomical knowledge,surgical training and clinical experience.

Neurite initiation is critical for neuronal morphogenesis and early neural circuit development. Recent studies showed that local actin aggregation underneath the cell membrane determined the site of neurite initiation. An immediately arising question is what signaling mechanism initiated actin aggregation. Here we demonstrate that local clustering of phosphatidylinositol 3,4-bisphosphate (PI(3,4)P 2 ), a phospholipid with relatively few known signaling functions, is necessary and sufficient for aggregating actin and promoting neuritogenesis. In contrast, the related and more extensively studied phosphatidylinositol 4,5-bisphosphate or phosphatidylinositol (3,4,5)-trisphosphate (PIP 3 ) molecules did not have such functions. Specifically, we showed that beads coated with PI(3,4)P 2 promoted actin aggregation and neurite initiation, while pharmacological interference with PI(3,4)P 2 synthesis inhibited both processes. PI(3,4)P 2 clustering occurred even when actin aggregation was pharmacologically blocked, demonstrating that PI(3,4)P 2 functioned as the upstream signaling molecule. Two enzymes critical for PI(3,4)P 2 generation, namely, SH2 domain-containing inositol 5-phosphatase and class II phosphoinositide 3-kinase α, were complementarily and non-redundantly required for actin aggregation and neuritogenesis, as well as for subsequent dendritogenesis. Finally, we demonstrate that neural Wiskott-Aldrich syndrome protein and the Arp2/3 complex functioned downstream of PI(3,4)P 2 to mediate neuritogenesis and dendritogenesis. Together, our results identify PI(3,4)P 2 as an important signaling molecule during early development and demonstrate its critical role in regulating actin aggregation and neuritogenesis.

Analyses of 16S rRNA and housekeeping genes (HKGs) were valuated as identification markers for pathogenic Aeromonas isolated from diseased eels. The interrelationships of 32 Aeromonas strains which had been verified as pathogens to eels were studied using phylogenetic analysis with 16S rRNA and HKG sequences (cpn60, gyrB, rpoB and dnaJ) and identified by Biolog automatic microbiology analysis system (gene III). From the analysis of 5 genes, the mean gene divergences of 16S rRNA, cpn60, gyrB, rpoB and dnaJ in 32 isolates were 1.4 ± 0.2%, 7.1 ± 0.7%, 5.2 ± 0.5%, 2.2 ± 0.4% and 6.8 ± 0.5%, respectively. The results of comparative phylogeny between nucleotide based analyses (excluding the third codon position) of four HKGs with the sequences from 55 strains of Aeromonas (including 23 referenced strains of Aeromonas) showed cpn60 and dnaJ have higher discriminate power than gyrB and rpoB comparing with the taxonomical identification by Biolog system. In addition, amino acid sequences of concatenated cpn60-rpoB-gyrB is a good method for Aeromonas pathogens identification. This study showed analysis of HKG sequences can be used as an alternative method for sound identification of bacterial pathogens isolated from diseased eels in China., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Fractional flow reserve (FFR)-guided revascularization strategy is popular in coronary intervention. However, the feasibility of assessing stenotic severity in intracranial large arteries using pressure gradient measurements still remains unclear., Methods: Between March 2013 and May 2014, 12 consecutive patients with intracranial large artery stenosis (including intracranial internal carotid artery, middle cerebral M1 segment, intracranial vertebral artery, and basilar artery) were enrolled in this study. The trans-stenotic pressure gradient was measured before and/or after percutaneous transluminal angioplasty and stenting (PTAS), and was then compared with percent diameter stenosis. A Pd /Pa cut-off of ≤0.70 was used to guide stenting of hemodynamically significant stenoses. The device-related and procedure-related serious adverse events and recurrent cerebral ischemic events were recorded., Results: The target vessel could be reached in all cases. No technical complications occurred due to the specific study protocol. Excellent pressure signals were obtained in all patients. For seven patients who performed PTAS, the mean pre-procedural pressure gradient decreased from 59.0 ± 17.2 to 13.3 ± 13.6 mm Hg after the procedure (P < 0.01). Only one patient who refused stenting experienced a TIA event in the ipsilateral MCA territory. No recurrent ischemic event was observed in other patients., Conclusion: Mean trans-stenotic pressure gradients can be safely and easily measured with a 0.014-inch fluid-filled guide wire in intracranial large arteries. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

A salient feature of neurons is their intrinsic ability to grow and extend neurites, even in the absence of external cues. Compared to the later stages of neuronal development, such as neuronal polarization and dendrite morphogenesis, the early steps of neuritogenesis remain relatively unexplored. Here we showed that redistribution of cortical actin into large aggregates preceded neuritogenesis and determined the site of neurite initiation. Enhancing actin polymerization by jasplakinolide treatment effectively blocked actin redistribution and neurite initiation, while treatment with the actin depolymerizing agents latrunculin A or cytochalasin D accelerated neurite formation. Together, these results demonstrate a critical role of actin dynamics and reorganization in neurite initiation. Further experiments showed that microtubule dynamics and protein synthesis are not required for neurite initiation, but are required for later neurite stabilization. The redistribution of actin during early neuronal development was also observed in the cerebral cortex and hippocampus in vivo.

Background/aims: FBXO6 is the substrate recognition component of a Skp1-Cullin1-F-box protein (SCF) ubiquitin E3 ligase complex, recognizing the chitobiose in unfolded N-glycoprotein to target glycoproteins for polyubiquitination and degradation. Although how FBXO6 recognizes glycoprotein has been fully investigated, the ubiquitination substrates of FBXO6 remain largely unknown. Previously, we have systematically identified the glycoproteins that interact with FBXO6 in an N-glycan dependent manner by LC/MS spectrum and confirmed the interaction between FBXO6 and glycosylated Ero1L, a protein disulfide oxidase in endoplasmic reticulum (ER)., Methods: The relationship between endogenous Ero1L and exogenous Flag-FBXO6 were determined by Western blot. In vivo ubiquitination assay was used to detect the direct effect of FBXO6 in the regulation of Ero1L. Both CCK8 and FACS assays were used to determine the apoptosis ratio of cells after treatments., Results: Ero1L is a ubiquitination substrate of FBXO6. FBXO6 mediates the degradation of Ero1L through a ubiquitylation-dependent pathway. Overexpression of FBXO6 increased the polyubiquitination and decreased the stability of Ero1L, whereas inhibition of FBXO6 prolonged the half-life of Ero1L. Functionally, we show that FBXO6 inhibits ER stress-induced apoptosis by modulating the protein level of Ero1L., Conclusion: Collectively, our results demonstrate FBXO6 as a functional E3 ubiquitin ligase for Ero1L that plays a critical role in inhibiting ER stress-induced apoptosis., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Objective: To explore the clinical efficacies of endovascular therapy for traumatic arterial intima injury, arterial pseudoaneurysm and arteriovenous fistula., Methods: From October 2009 to December 2011, 24 patients of arterial intima injury, arterial pseudoaneurysm and arteriovenous fistula underwent endovascular therapy including embolism and stent implantation, etc., Results: Among them, 14 patients were punctured directly and another 10 were punctured after the exposure of arteries. The interventions included embolism (n = 3), embolism plus covered stent implantation (n = 2), covered stent implantation (n = 12) and bare stent implantation (n = 7). And the surgical success rate was 100%. After endoluminal treatment, arterial blood flow recovered, arterial pseudoaneurysm shrank, local pain relieved and venous blood pressure decreased., Conclusion: As an effective therapy for traumatic arterial intima injury, arterial pseudoaneurysm and arteriovenous fistula, endovascular therapy has minimal trauma, fewer complications and satisfactory outcomes.

Doxazosin used in benign prostatic hyperplasia has the side effects of causing hypotension and the risk of heart failure. The 3 targets of α(1A)-adrenoceptors (in the prostate), α(1D)-adrenoceptors (in the aorta), and an unknown mechanism (in the heart) are involved, respectively. We hypothesized that there is a chiral recognition of doxazosin enantiomers in the 3 targets. Using isolated rat aorta (α(1D)-adrenoceptors) and rabbit prostate (α(1A)-adrenoceptors), we examined pA(2) and pK(B) values of doxazosin enantiomers. We observed chronotropic and inotropic effects of doxazosin enantiomers in isolated rat and rabbit heart tissues. (-)Doxazosin and (+)doxazosin produced a shift to the right of concentration-contraction curves for noradrenalin (aorta) and phenylephrine (prostate smooth muscle). The pA(2) value of (-)doxazosin (8.625 ± 0.053) was smaller than (+)doxazosin (9.503 ± 0.051) in rat aorta, but their pK(B) values in rabbit prostate were the same. In rat and rabbit heart tissues, (+)doxazosin (3-30 µmol·L(-1)) significantly decreased atrial rate, and produced negative inotropic effects; however, (-)doxazosin did not affect the atrial rate, and produced positive inotropic effects in the atria. Thus, the chiral carbon atom of doxazosin does not affect its activity at the therapeutic target of α(1A)-adrenoceptors in the prostate, but significantly changes its blocking activity against α(1D)-adrenoceptors in the aorta, and produces opposite inotropic effects in the atria via an α(1)-adrenoceptor-independent mechanism.

High-mobility group box 1 (HMGB1) is a nuclear factor released extracellularly as an early endogenous alarmin of inflammation following injury and as a late mediator of lethality in sepsis. Although HMGB1 has been implicated in acute lung injury, rheumatoid arthritis, and allograft rejection, its role in T-cell mediated hepatitis remains obscure. Here, we investigated the role and the underlying mechanisms of HMGB1 in concanavalin A (Con A) induced hepatic injury. We demonstrate that high levels of HMGB1 were detected in the necrotic area and in the cytoplasm of hepatocytes after Con A treatment. Administration of exogenous recombinant HMGB1 enhanced Con A-induced hepatitis, while blockade of HMGB1 protected animals from T cell-mediated hepatitis as evidenced by decreased serum transaminase, associated with reduced hepatic necrosis and mortality. Blockade of HMGB1 by a neutralizing antibody inhibited proinflammatory cytokine production, NFκB activity, and the late stage of T/NKT cell activation. These finding thus suggest a pivotal factor of HMGB1 in Con A-induced hepatitis. Blockage of extracellular HMGB1 may represent a novel therapeutic strategy to prevent hepatic injury in T cell-mediated hepatitis.

T cell-mediated hepatic damage plays a key role in the pathogenesis of liver diseases such as autoimmune hepatitis, viral hepatitis and acute liver failure. CpG-containing oligodeoxynucleotides (CpG ODN), a ligand for toll-like receptor (TLR) 9, is widely used as an immunological adjuvant. In the present study, we investigated the effect of CpG ODN on T cell-mediated liver injury in a murine model of concanavalin A (Con A)-induced hepatitis. We found that the aminotransferase level was significantly decreased in CpG ODN pretreated mice and the survival of the mice was markedly prolonged. CpG ODN pretreatment inhibited NF-kappaB DNA binding activity. As a result, the systemic/liver levels of TNF-alpha and IFN-gamma were significantly suppressed. Furthermore, the activation of inflammatory cells was diminished by CpG ODN pretreatment. These results suggest that CpG ODN pretreatment protects the mice from Con A-induced liver injury via inhibiting hepatocyte apoptosis, inflammation and activation of lymphocytes.

We explored the effects of recombinant A-box (rA-box), a specific blockade for endogenous high mobility group box 1 (HMGB1) protein, on acute lung inflammation induced by lipopolysaccharide (LPS) in vivo. Acute lung injury (ALI) was produced successfully by intratracheal administration of LPS (10 microg/mouse) in male BALB/c mice. rA-box (0.3, 0.6 mg/mouse, i.p.) was administered 30 min prior to or 2 h after LPS exposure. Bronchoalveolar lavage fluid (BALF) was obtained to measure chemokines, proinflammatory cytokines, total cell counts and proteins at the indicated time points. It was found that rA-box caused a significant reduction in the total cells and neutrophils in BALF, a significant reduction in the W/D ratio and protein leakage at 24 h after LPS challenge. In addition, rA-box was also believed to have downregulated the expression of LPS-induced chemokines (keratinocyte-derived chemokine) and proinflammatory cytokines, including early mediator TNF-a and late mediator HMGB1. These findings confirm the significant protection of rA-box against LPS-induced ALI, and the effect mechanism of rA-box was associated with decreasing the expression of chemokines and proinflammatory cytokines.

Doxazosin, a high selective alpha1-adrenoceptor antagonist, is considered as the first-line therapy for the patients with benign prostatic hyperplasia (BPH) and also produce several side effects in cardiovascular system. In this study, we observed the isometric vasoconstrictive responses of the rabbit isolated arterial rings to electric field stimulation and noradrenaline ( NA ) to study the effects of R-doxazosin ( R-DOX ) and S-doxazosin ( S-DOX ) on the alpha1-adrenoceptor-regulated vasoconstrictive responses in the rabbit isolated ear artery, mesenteric artery and pulmonary artery, and the effects of higher concentration of S-DOX and R-DOX on presynaptic alpha2-adrenoceptor-regulated purinergic vasoconstriction in the rabbit isolated saphenous artery. We found that R-DOX and S-DOX competitively inhibited the vasoconstriction induced by NA in the rabbit isolated ear artery, mesenteric artery and pulmonary artery. The pA2 values of R-DOX and S-DOX against NA in the rabbit isolated ear artery, mesenteric artery and pulmonary artery were 7. 91 +/- 0. 03 and 7. 53 +/- 0. 05, 7. 80 +/- 0. 05 and 7. 29 +/-0. 07, 8. 32 +/- 0. 06 and 7. 97 +/- 0. 07, respectively. The pA2 values of R-DOX in the three arterial preparations were significantly higher than those of S-DOX (P < 0. 01). R-DOX and S-DOX at the concentrations of 0. 1 - 10 micromol x L (-1) did not affect the vasoconstriction induced by electric stimulation in the rabbit isolated saphenous artery. R-DOX and S-DOX at 100 micromol x L(-1) in the rabbit isolated saphenous artery completely inhibited the vascular responses to exogenous NA, but did not affect the vascular responses to exogenous adenosine triphosphate (1 mmol x L(-1) ). It is reasonable to suggest that R-DOX and S-DOX competitively inhibit the vasoconstriction induced by NA in the rabbit ear artery, mesenteric artery and pulmonary artery, and the pA2 values of S-DOX are significantly lower than those of R-DOX. The higher concentration (10 micromol x L(-1)) of R-DOX and S-DOX does not affect the presynaptic alpha2-adrenoceptors at sympathetic nerve terminals of the rabbit saphenous artery.

Aim: To study chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats., Methods: In anesthetized rats, the carotid blood pressure, left ventricular pressure of the heart and the urinary bladder pressure were recorded., Results: Administration of S-doxazosin at 0.25, 2.5, 25, and 250 nmol/kg iv produced a dose-dependent decrease in blood pressure, but its depressor effect was significantly weaker than that induced by R-doxazosin and racemic-doxazosin (rac-doxazosin), and the ED(30) values (producing a 30% decrease in mean arterial pressure) of R-doxazosin, rac-doxazosin and S-doxazosin were 15.64, 45.93, and 128.81, respectively. Rac-doxazosin and its enantiomers administered cumulatively in anesthetized rats induced a dose-dependent decrease in the left ventricular systolic pressure and +/-dp/dt(max), and the potency order of the 3 agents was R-doxazosin > rac-doxazosin > S-doxazosin. Rac-doxazosin and its enantiomers decreased the vesical micturition pressure dose-dependently at 2.5, 25, and 250 nmol/kg, and the inhibitory potency among the 3 agents was not significantly different., Conclusion: S-doxazosin decreases the carotid blood pressure and left ventricular pressure of the heart less than R-doxazosin and rac-doxazosin, but its effect on the vesical micturition pressure is similar to R-doxazosin and rac-doxazosin, indicating that S-doxazosin has chiral selectivity between cardiovascular system and urinary system in anesthetized rats.

Objective: To investigate the characteristics of erectile dysfunction (ED) in old males with lacunar infarction., Methods: A total of 38 old patients ages from 60 to 70 years were involved. The questionnaire of international index of erectile function 5 (IIEF -5) was used to determine the status and severity of ED. According to the focus of infarction on MRI, the patients were divided into two groups, Group I with lacunar infarction and minor neurological deficits, and Group II with none. The total IIEF-5 scores were compared between the two groups and repeatedly evaluated six months after discharge., Results: According to the total scores of IIEF-5, the prevalence of ED in Group II (95%) was higher, and the incidence of severe ED was significantly increased (60.0% vs. 44.4%, P < 0.05) as compared with Group II. In both the two groups, severe ED was more often seen in diabetic patients. At six months after discharge, the total scores of IIEF-5 were significantly increased (11.2 +/- 3.2 vs. 15.6 +/- 2.2, P < 0.05)., Conclusion: ED is significantly increased in old males with lacunar infarction, and it is more severe in diabetic patients. Post-stroke rehabilitation care helps to improve ED.

Objective: To explore the effects of surgical procedure combined with the intravascular minimal invasive technique for the treatment of deep vein thrombosis (DVT) of lower extremity., Methods: At the curse of disease from six hours to ninety days, one hundred and two patients with DVT including one hundred and three lower extremities had received surgical procedure and intravascular minimal invasive treatment., Results: There were not procedure-related morbidities in 102 cases, and symptoms disappeared, all procedures were successful based on angiography. The detecting head for the intravascular ultrasound ablation was entered to inferior vena cava (IVC) in 74 cases (78%), Forgarty catheter was entered to IVC in 21 cases (21%), the stenosis in the confluence of the common iliac vein and IVC was dilated by sacculus rotundus catheter in 89 cases (88%), including 9 patients underwent percutaneous transluminal stenting. One hundred and two patients followed up for twenty months, follow-up by angiography showed no restenosis in 91 cases, restenosis in ilio-femoral vein in 1 cases, and thrombus recontouring in 4 cases, as well as 6 cases died caused by primary disease., Conclusion: Surgical procedure combined with the intravascular minimal invasive technique is a safe and effective therapeutic method for DVT.

Objective: To investigate the association of p53 codon 72 and p53 intron 3 (PIN3) polymorphism with susceptibility to epithelial ovarian cancer in northern Chinese women., Methods: p53 codon 72 and PIN3 genotyping was performed by DNA fragments with sequence specific primers among 124 patients with ovarian cancer and 128 healthy control women., Results: The frequency of the Pro and Arg allele among ovarian cancer patients and healthy controls were 53.2%, 46.8% and 46.1%, 53.9%. No significant difference in distribution of allelotype was shown between the two groups (chi(2) = 2.563, P = 0.109). The genotype frequencies of Pro/Pro, Pro/Arg, and Arg/Arg among ovarian cancer and healthy controls were 29.0%, 48.4%, 22.6% and 21.1%, 50.0%, 28.9% respectively. No significant difference was shown between the cases and controls (chi(2) = 2.598, P = 0.273). When the epithelial ovarian cancer patients were grouped according to the pathological characteristics, no significant difference was observed between the patients with serous cystadenocarcinoma or endometrioid carcinoma and the control group or between the two carcinoma groups for p53 codon 72 Pro/Arg (P > 0.05). When the epithelial ovarian cancer patients were divided into two subgroups according to the International Federation of Gynecology and Obstetrics (FIGO) standard, there was a significant difference between the early group (I approximately II) and the late group (III approximately IV) for Arg allelotype and Arg/Arg genotype (chi(2) = 7.494, P = 0.006 and chi(2) = 8.318, P = 0.004). The frequency of A, A'allelotype among ovarian cancer patients and healthy controls was 94.8%, 5.2% and 94.5%, 5.5%, no significant difference was shown between two groups (chi(2) = 0.013, P = 0.91). The genotype frequency of AA, AA', A'A' was not significantly different between the ovarian cancer and healthy controls (chi(2) = 0.301, P = 0.583). There was no significant difference in the frequencies of allelotypes and genotypes between patients with serous systadenocarcinoma and those with endometrioid carcinoma and between patients with ovarian cancers and the control subjects (all P > 0.05). The frequencies of allelotypes and genotypes were not significantly different between early and late ovarian cancers (chi(2) = 0.014, P = 0.906 and chi(2) = 0.137, P = 0.711)., Conclusions: In northern Chinese women, p53 codon 72 Pro/Arg and p53 PIN3 gene polymorphisms are not associated with development of ovarian cancer. Arg/Arg genotype may be used as a stratification marker according to the standards of FIGO for ovarian cancer.