Relationship between social support and self-care ability among patients with breast cancer during rehabilitation: The multiple mediating roles of resilience and depression.

AIMS: To identify the multiple mediating effects of resilience and depression between social support and self-care ability among patients with breast cancer during rehabilitation to provide reference for developing and implementing targeted interventions. DESIGN: A cross-sectional study reported according to the STROBE checklist. METHODS: A convenience sample of 320 patients with breast cancer during rehabilitation was recruited from one hospital in China. Data were collected from April to August 2022 using a self-report questionnaire, including the demographic and clinical information, Appraisal of Self-Care Agency Scale-Revised, Multidimensional Scale of Perceived Social Support, Connor-Davidson Resilience Scale-10 item, and Patient Health Questionnaire-9. The mediation analysis was conducted using the SPSS Process macro. RESULTS: Self-care ability was positively associated with social support (ß = .229) and resilience (ß = .290), and negatively associated with depression (ß = -.208). The relationship between social support and self-care ability was mediated by resilience and depression, respectively, and together in serial. The multiple mediating effects accounted for 34.0% of the total effect of social support on self-care ability. CONCLUSION: Our findings identify resilience and depression as multiple mediators between social support and self-care ability and highlight the important roles of social support, resilience and depression in improving self-care ability. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers should pay great attention to the underlying mechanisms of how social support affects patients' self-care ability during breast cancer rehabilitation. Integrated intervention programmes targeted at enhancing social support, building resilience and alleviating depression might be beneficial to the improvement of self-care ability. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. REPORTING METHOD: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cross-sectional studies was applied to report the results.

Efficacy of early administration of sacubitril/valsartan after coronary artery revascularization in patients with acute myocardial infarction complicated by moderate-to-severe mitral regurgitation: a randomized controlled trial.

Effects of angiotensin receptor/neprilysin inhibitors (ARNI) on ventricular remodeling in patients with heart failure, especially heart failure with reduced ejection fraction (HFrEF), are better than those of angiotensin-converting enzyme inhibitors (ACEI). Acute myocardial infarction (AMI) complicated by mitral regurgitation exacerbates ventricular remodeling and increases the risk of heart failure. There is limited evidence on the effects of early administration of ARNI in patients with AMI complicated by mitral regurgitation. The aim of this trial was to examine the effectiveness and the safety of early administration of sacubitril/valsartan after coronary artery revascularization in patients with AMI complicated by moderate-to-severe mitral regurgitation. This was a randomized, single-blind, parallel-group, controlled trial. From June 2021 to June 2022, we enrolled 142 consecutive patients with AMI complicated by moderate-to-severe mitral regurgitation and followed them for 12 months. The patients received standard treatment for AMI and were randomly assigned to receive ARNI or benazepril. The primary efficacy end points were the differences in mitral regurgitant jet area (MRJA), mitral regurgitant volume (MRV), concentration of n-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume and end-systolic volume (LVEDV and LVESV) between groups and within groups at baseline, 1, 3, 6, and 12 months. Secondary end points included the rates of heart failure hospitalization, all-cause mortality, refractory angina, malignant arrhythmias, recurrent myocardial infarction, and stroke. Safety end points included the rates of hyperkalemia, renal dysfunction, hypotension, angioedema, and cough. The ARNI group had significantly lower NT-proBNP levels than the benazepril group at 1 month and later (P < 0.001). MRJA and MRV significantly improved in the ARNI group compared with the benazepril group at 12 months (MRJA: - 3.21 ± 2.18 cm2 vs. - 1.83 ± 2.81 cm2, P < 0.05; MRV: - 27.22 ± 15.22 mL vs. - 13.67 ± 21.02 mL, P < 0.001). The ARNI group also showed significant reductions in LVEDV and LVESV (P < 0.05) and improvement in LVEF (P < 0.05). Secondary end point analysis showed a significantly higher rate of heart failure hospitalization in the benazepril group compared with the ARNI group (HR = 2.03, 95% CI 1.12-3.68, P = 0.021). Safety end point analysis showed a higher rate of hypotension in the ARNI group (P < 0.05). Early use of sacubitril/valsartan after coronary artery revascularization in patients with AMI complicated by moderate-to-severe mitral regurgitation can significantly reduce mitral regurgitation, improve ventricular remodeling, and decrease heart failure hospitalization. Nevertheless, caution is needed to avoid hypotension. Chinese Clinical Trial Registry (ChiCTR2100054255) registered on December 11, 2021.

Early Depletion of Neutrophils Reduces Retinal Inflammation and Neovascularization in Mice with Oxygen-Induced Retinopathy.

Retinal inflammation is a central feature of ocular neovascular diseases such as diabetic retinopathy and retinopathy of prematurity, but the contribution of neutrophils to this process is not fully understood. We studied oxygen-induced retinopathy (OIR) which develops in two phases, featuring hyperoxia-induced retinal vaso-obliteration in phase I, followed by retinal neovascularization in phase II. As neutrophils are acute responders to tissue damage, we evaluated whether neutrophil depletion with an anti-Ly6G mAb administered in phase I OIR influenced retinal inflammation and vascular injury. Neutrophils were measured in blood and spleen via flow cytometry, and myeloperoxidase, an indicator of neutrophil activity, was evaluated in the retina using Western blotting. Retinal vasculopathy was assessed by quantitating vaso-obliteration, neovascularization, vascular leakage, and VEGF levels. The inflammatory factors, TNF, MCP-1, and ICAM-1 were measured in retina. In the OIR controls, neutrophils were increased in the blood and spleen in phase I but not phase II OIR. In OIR, the anti-Ly6G mAb reduced neutrophils in the blood and spleen, and myeloperoxidase, inflammation, and vasculopathy in the retina. Our findings revealed that the early rise in neutrophils in OIR primes the retina for an inflammatory and angiogenic response that promotes severe damage to the retinal vasculature.

Detection of Specific Volatile Organic Compounds in Tribolium castaneum (Herbst) by Solid-Phase Microextraction and Gas Chromatography-Mass Spectrometry.

The red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae), is a major storage pest that could lead to a wide range of damage. Its secretions have a significant impact on the quality of stored grain and food, leading to serious food safety problems such as grain spoilage and food carcinogenesis. This study investigates new detection techniques for grain storage pests to improve grain insect detection in China. The primary volatile organic chemicals (VOCs) in these secretions are identified using headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS). The specific VOCs that are unique to T. castaneum are selected as criteria for determining the presence of T. castaneum in the granary. To obtain more specific VOCs, experiments were designed for the analysis of T. castaneum samples under different extraction times, two types of SPME fibers and two GC-MS devices of different manufacturers. The experimental results showed that 12 VOCs were detected at relatively high levels, seven of which were common and which were not detected in other grains and grain insects. The seven compounds are 1-pentadecene, 2-methyl-p-benzoquinone, 2-ethyl-p-benzoquinone, 1-hexadecene, cis-9-tetradecen-1-ol, m-cresol and paeonol. These seven compounds can be used as volatile markers to identify the presence of T. castaneum, which could serve as a research foundation for the creation of new techniques for T. castaneum monitoring.

Assessment of Trimetazidine Treatment in Acute Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention.

Aims: Trimetazidine (TMZ) is effective at improving clinical outcomes in chronic heart failure and stable coronary artery disease patients. However, no single study has comprehensively evaluated the efficacy of TMZ in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI). Methods: We enrolled 401 Chinese patients. All patients received the same drug prescription except for TMZ. In blinded fashion, patients were randomized to either a control or an experimental group in which 60 mg TMZ was provided at admission and then at 20 mg three times a day thereafter. At 2 and/or 6 days, we evaluated creatine kinase (CK and CK-MB), cardiac troponin I (cTnI), C-reaction protein (CRP), serum tumor necrosis factor (TNF-α), serum creatinine (Cr), serum urea, glucose, glutamic pyruvic transaminase (ALT), and glutamic oxaloacetic transaminase (AST). Additionally, by echocardiography, we assessed left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), and cardiac output (CO). Results: CK and CKMB, which were recorded on the second day in the hospital (each p=0.022), and cTNI, which was recorded on the sixth day in the hospital (p=0.003), were reduced with TMZ treatment compared to control. In addition, ALT and AST (p=0.001, p=0.000, respectively) and glucose after 6 days (p=0.011) were significantly lower in the study group than in the control group. Furthermore, LVEF after 10-14 days and 6 months after discharge (p=0.039 and p=0.047, respectively) was increased with TMZ treatment. The effects of TMZ on CRP, TNF-α, Cr, urea, LVEDD, and CO were not significant (all p > 0.05). Conclusions: For AMI patients undergoing PCI, TMZ reduced circulating biomarkers of myocardial infarction, reduced values of ALT, AST, and glucose, and improved cardiac function compared with the control group.

Clemastine Rescues Chemotherapy-Induced Cognitive Impairment by Improving White Matter Integrity.

With the improvement of cancer treatment techniques, increasing attention has been given to chemotherapy-induced cognitive impairment through white matter injury. Clemastine fumarate has been shown to enhance white matter integrity in cuprizone- or hypoxia-induced demyelination mouse models. However, whether clemastine can be beneficial for reversing chemotherapy-induced cognitive impairment remains unexplored. In this study, the mice received oral administration of clemastine after chemotherapy. The open-field test and Morris water maze test were used to evaluate their anxiety, locomotor activity and cognitive function. Luxol Fast Blue staining and transmission electron microscopy were used to detect the morphological damage to the myelin. Demyelination and damage to the mature oligodendrocytes and axons were observed by immunofluorescence and western blotting. Clemastine significantly improved their cognitive function and ameliorated white matter injury in the chemotherapy-treated mice. Clemastine enhanced myelination, promoted oligodendrocyte precursor cell differentiation and increased the neurofilament 200 protein levels in the corpus callosum and hippocampus. We concluded that clemastine rescues cognitive function damage caused by chemotherapy through improving white matter integrity. Remyelination, oligodendrocyte differentiation and the increase of neurofilament protein promoted by clemastine are potential strategies for reversing the cognitive dysfunction caused by chemotherapy.

Transurethral resection in women with symptomatic keratinizing squamous metaplasia of urinary bladder: A retrospective study of 92 cases.

OBJECTIVES: To investigate the efficacy of transurethral resection (TUR) on relieving urinary symptoms in patients with keratinizing squamous metaplasia (KSM) of the urinary bladder. METHODS: Data were analyzed from a retrospective study of patients receiving transurethral bipolar plasma resection (bi-TUR) treatment for symptomatic KSM. Urinary symptoms were assessed by the International Prostate Symptom Score (IPSS) and a numeric rating scale pain score. Efficacy was assessed using the IPSS to determine changes from baseline in lower urinary tract symptoms (LUTS). Self-reported quality of life (QoL) was assessed by the last question of the IPSS questionnaire. RESULTS: A total of 92 female patients were included in the analysis. The median age was 42 years. LUTS, pain, and hematuria were the most common symptoms that affected patients. The median follow-up duration was 51 months. There were significant improvements in LUTS from baseline IPSS after TUR (P < .001). The percentage of the patients with moderate to severe LUTS went down from 52.2% to 18.5%. The median Numeric Rating Scale (NRS)-11 pain score reduced from 3 at baseline to 0 at the last visit. Twenty-one out of 40 patients reported that the pain symptoms disappeared completely. No patients reported hematuria symptoms at the final follow-up. Improvement of self-reported QoL was significant (P < .001). A total of 57.6% of patients reported an improvement, 26.1% of patients reported no improvement, and 16.3% reported deterioration. CONCLUSIONS: Bi-TUR therapy significantly relieved urinary symptoms in women with KSM. Improvement of QoL was acceptable with a success rate of 57.6%. Considering the very low complication rate, our study supported bi-TUR as an alternative treatment for patients who are resistant to medical therapy.

The effect of trimetazidine treatment in patients with type 2 diabetes undergoing percutaneous coronary intervention for AMI.

PURPOSE: Trimetazidine (TMZ) improves clinical outcomes in patients with chronic heart failure and stable coronary artery disease. No study has yet evaluated the efficacy of TMZ in type 2 diabetes patients with acute myocardial infarction (AMI) undergoing Percutaneous Coronary Intervention (PCI). We performed this study to evaluate the efficacy TMZ in DM patients with AMI undergoing PCI, such as the effect on reductions in myocardial enzyme, improvements in liver function, modulation of glucose levels, and improvement in cardiac function. METHODS: For this randomized study, we enrolled 173 AMI patients with type 2 diabetes undergoing PCI between January 1, 2014, and January 1, 2016. All patients received aspirin and ticagrelor upon admission and throughout their hospitalization. Patients in the experimental group were treated with a loading dose of 60mg TMZ at admission, and 20 mg TMZ three times a day thereafter. 89 patients were included in experimental group, and 84 patients were included in control group. All patients received PCI treatments. The endpoints evaluated were serum creatine kinase and its isoenzyme (CK and CK-MB), cardiac troponin I (cTNI), serum creatinine (Cr), serum urea, blood glucose, serum glutamic pyruvic transaminase (ALT), serum glutamic oxaloacetictransaminase (AST), left atrial dimension (LA), left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), and cardiac output (CO). FINDINGS: Compared with the control group, TMZ treatment significantly reduced CK and CK-MB on the second day in hospital ([797±582] vs. [1092±1114]; [80±60] vs. [105±100]; p=0.029, p=0.041, respectively), and cTNI after one and six days in hospital ([13.5±12.7] vs. [19.8±19.2]; [3.3±3.2] vs. [4.8±4.7]; two-tailed p=0.012). In addition, TMZ significantly lowered liver enzymes (ALT, AST) at 6days ([29.0±11.6] vs. [42.4±24.5]; [39.8±17.3] vs. [69.2±70.0]; two-tailed p=0.000), lowered glucose after 6days ([6.80±2.12] vs. [7.59±2.24]; p=0.019), and increased LVEF after ten to fourteen days ([58.4±8.6] vs. [54.9±8.4]; p=0.008). There were no significant effect on Cr and serum urea (p=0.988, p=0.569, respectively), nor on LA, LVEDD, and CO ([36.3±4.5] vs. [37.0±4.1], p=0.264; [52.0±4.9] vs. [53.1±4.6], p=0.128; [5.4±0.9] vs. [5.4±0.9], p=0.929, respectively). IMPLICATIONS: Among type 2 diabetic patients with AMI undergoing PCI, TMZ significantly reduces serum myocardial enzyme, improves liver function, adjusts blood glucose and improves cardiac function.

Assessment of Ticagrelor Versus Clopidogrel Treatment in Patients With ST-elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

AIMS: Ticagrelor improves the clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). However, few studies have directly compared the efficacy and safety of ticagrelor against clopidogrel, an oral, thienopyridine-class antiplatelet drug. This study compared the efficacy and safety of ticagrelor and clopidogrel in patients with STEMI undergoing PPCI. METHODS: We enrolled 400 patients with STEMI undergoing PPCI at the Zhujiang Hospital of Southern Medical University and the First Hospital of Qinhuangdao, China, between January 01, 2013 and April 30, 2015. All patients received 300 mg of aspirin and were randomized to receive one of the following treatments: (1) a loading dose of clopidogrel (600 mg) before PPCI followed by clopidogrel (75 mg once daily for 1 year) post PPCI or (2) a loading dose of ticagrelor (180 mg) before PPCI followed by ticagrelor (90 mg twice daily for 1 year) post PPCI. Some patients were treated by intracoronary bolus of a glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor [tirofiban (10 µg/kg) plus maintenance infusion (0.15 µg·kg·min) for 24-36 hours] in accordance with specified guidelines. The primary end points evaluated were major adverse cardiovascular and cerebrovascular event (MACCE) [defined as a composite of overall death, myocardial infarction (MI), unplanned revascularization, or stroke], stent thrombosis, and the composite end point of CV death, nonfatal MI, and stroke. The supplemental use of GPIIb/IIIa inhibitors in the clopidogrel and ticagrelor groups was monitored as another study end point, although the secondary safety end point evaluated was the incidence of bleeding events. RESULTS: Compared with the clopidogrel-treated group, ticagrelor treatment significantly reduced the incidence of MACCE [5 vs. 14; odds ratio (OR), 0.341; 95% confidence interval (CI), 0.120-0.964; P = 0.034] and the composite end points of cardiovascular death, nonfatal MI, and stroke (4 vs. 13; OR, 0.294; 95% CI, 0.094-0.916; P = 0.026). Fewer patients in the ticagrelor group received GPIIb/IIIa inhibitors after PPCI compared with those in the clopidogrel group (10 vs. 21; OR, 0.449; 95% CI, 0.206-0.979; P = 0.040). However, there were no significant differences between the groups in the incidences of all-cause mortality, nonfatal MI, unplanned revascularization, stroke, stent thrombosis (P = 0.522, P = 0.246, P = 0.246, P = 0.217, P = 0.246, respectively), or bleeding events (10 vs. 7; OR, 1.451; 95% CI, 0.541-3.891; P = 0.457). CONCLUSIONS: Among patients with STEMI undergoing PPCI, ticagrelor reduces the incidence of MACCE and the composite end point of cardiovascular death, nonfatal MI, and stroke compared with clopidogrel. Ticagrelor also reduces the need for GPIIb/IIIa inhibitors. However, no significant difference was observed in the risk of bleeding between the 2 groups.

Helix B Surface Peptide Protects Cardiomyocytes Against Hypoxia/Reoxygenation-induced Apoptosis Through Mitochondrial Pathways.

BACKGROUND: Helix B surface peptide (HBSP), a newly developed tissue-protective erythropoietin derivative, has beneficial effects on myocardial ischemia. This study aimed to investigate the cardio-protective effects of HBSP against hypoxia/reoxygenation (H/R) injury and its possible mechanism. METHODS: A rat-derived cardiomyocyte cell line (H9C2 cells) were established and pretreated with HBSP. The pretreated primary cultures were subjected to H/R and monitored for cell viability using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Intracellular reactive oxygen species (ROS) levels, apoptosis, and mitochondrial membrane potential (ΔΨm) were detected by flow cytometry. The expression of cytochrome C and Bcl-2 family proteins, as well as the activities of caspases 3 and 9 were determined by Western blot analysis and a colorimetric method, respectively. RESULTS: HBSP reduced apoptotic cells in cardiomyocytes subjected to H/R. In HBSP-treated cardiomyocytes, the H/R-induced mitochondrial ROS production, ΔΨm collapse, and cytochrome C release from mitochondria to the cytosol significantly decreased. Moreover, HBSP inhibited the activation of caspases 9 and 3, as well as the alteration of Bcl-2 family proteins, which were induced by H/R. CONCLUSIONS: These results indicated that HBSP has protective effects against H/R-induced apoptosis by regulating the mitochondrial pathway. This mechanism involves inhibiting mitochondrial ROS generation, inhibiting caspase-3 activity, reducing ΔΨm collapse, reducing cytochrome release, and balancing anti and proapoptotic Bcl-2 family proteins.

Inflammatory myofibroblastic tumor of the urinary bladder in a patient with the left renal cell carcinoma: A case report.

This case report describes an inflammatory tumor of the urinary bladder along with left renal cell carcinoma which occurred in a 73-year-old male with a narrowed orificium urethrae internum and severe hyperplasia of the prostate gland. A biopsy was not obtained prior to surgery. An inflammatory myofibroblastic tumor (IMT) of the urinary bladder is a rare benign lesion, particularly in the elderly. To the best of our knowledge, there are no studies concerning IMTs of the urinary bladder in patients with unilateral renal cell carcinoma. A bladder lesion due to an IMT may be easily misdiagnosed as metastasis from left renal cell carcinoma due to the hypervascularity of the tumor. In this case, radical surgery of the cancer of the left kidney was performed by laparoscopy. Subsequently, after three weeks and according to the examination of the intraoperative frozen-sections, a partial cystectomy was performed. Thus, radical resection of the bladder and the associated complications were avoided.

Ewing sarcoma-primitive neuroectodermal tumor of the uterus: a clinicopathologic, immunohistochemical and ultrastructural study of one case.

INTRODUCTION: Ewing sarcoma-primitive neuroectodermal tumors (ES/PNET) constitute a family of neoplasms characterized by a continuum of neuroectodermal differentiation. ES/PNET of the uterus is rare. There are 43 cases published in the English literature as far as we know. We describe an additional case. CASE REPORT: A 56-year-old woman presented with a 2-month history of irregular menopausal vaginal bleeding. After surgical excision, microscopic, immunohistochemical and electron microscopic examination suggested the diagnosis of ES/PNET. The patient underwent combined chemotherapy consisting of ifosfamide, etoposide, and cisplatin. She was alive with no evidence of recurrence or metastasis after 41 months of the initial operation. DISCUSSION: In spite of the rarity of ES/PNET, we should consider it in the differential diagnosis of small cell neoplasms of the uterus.

Hydrogen sulfide regulates vascular endoplasmic reticulum stress in apolipoprotein E knockout mice.

BACKGROUND: Atherosclerosis is an important cardiovascular disease, becoming a major and increasing health problem in developed countries. However, the possible underlying mechanisms were not completely clear. In 2009, our research group first discovered that hydrogen sulfide (H(2)S) as a novel gastrotransmitter played an important anti-atherosclerotic role. The study was designed to examine the regulatory effect of hydrogen sulfide (H(2)S) on endoplasmic reticulum stress (ERS) in apolipoprotein E knockout (apoE(-/-)) mice fed a Western type diet. METHODS: C57BL/6 mice and homozygous apoE(-/-) mice were fed a Western type diet. C57BL/6 mice were injected intraperitoneally with normal saline (5 ml/kg per day) as control group. The apoE(-/-) mice were treated with the same dose of normal saline as the apoE(-/-) group, injected intraperitoneally with sodium hydrosulfide (NaHS, an H(2)S donor, 56 µmol/kg per day) as the apoE(-/-) + NaHS group and injected intraperitoneally with DL-propargylglycine (PPG, a cystathionine-γ-lyase inhibitor, 50 mg/kg, per day) as the apoE(-/-) + PPG group. After 10 weeks, the mice were sacrificed and the plasma lipids were detected. Sections of aortic root from these animals were examined for atherosclerotic lesions by HE and oil red O staining. The aortic ultrastructure and microstructure were analyzed with the help of light and electronic microscope. Glucose-regulated protein 78 (GRP78), caspase-12, copper-andzinc-containing superoxide dismutase (Cu/ZnSOD) and Mn-containing superoxide dismutase (MnSOD) protein expression in aortic tissues were detected with immunohistochemistry. The level of intracellular reactive oxygen species (ROS) were measured by using a commercial assay kit. RESULTS: Compared with control mice, apoE(-/-) mice showed increased plasma levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL), decreased high density lipoprotein (HDL), increased aortic plaque size, destroyed ultra-structure of aortic tissue, and increased expression of GRP78 and caspase-12 proteins. Compared with apoE(-/-) mice, H(2)S donor-treated apoE(-/-) mice showed a decreased plasma LDL level, lessened plaque necrosis and attenuated aortic ultra-structural disorder. H(2)S donor-treatment induced GRP78 expression but suppressed caspase-12 expression in aortic lesions. However, compared with apoE(-/-) mice, PPG treated apoE(-/-) mice showed enlarged plaque size, more severe ultrastructural disorder of the aortic tissue and reduced GRP78 staining in aortic lesions. The plasma lipids and the staining of caspase-12 in apoE(-/-) + PPG rats did not significantly differ from those in the apoE-/-mice. Consistently, H(2)S induced SOD expression, accompanied by a reduced level of ROS. CONCLUSION: H(2)S plays a regulatory role in aortic ERS and reduces atherosclerotic lesions in apoE(-/-) mice fed with a Western type diet.

Effects of N-acetylcysteine on Clara cells in rats with cigarette smoke exposure.

BACKGROUND: The number of Clara cells and the Clara cell 16-kDa protein (CC16) levels of the lung decrease in patients with chronic obstructive pulmonary disease (COPD). N-acetylcysteine (NAC) is a powerful antioxidant and can reduce the frequency of acute exacerbations of COPD. But the exact mechanism is unclear. The present study was designed to investigate the effects of NAC on Clara cells in rats with cigarette smoke exposure. METHODS: Eighteen adult male Wistar rats were randomly divided into 3 groups, 12 exposed to cigarette smoke (CS) thrice a day, 10 cigarettes for 30 minutes each time for 1 week, without (CS group) or with (CS + NAC group) oral intake of NAC 80 mg x kg(-1) x d(-1), and another 6 rats exposed to fresh air (control group). Clara cells were observed by an electron microscope. The mRNA expression of CC16 and CC16 protein in lungs were determined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry respectively. The glutathion (GSH) level in plasma and lung tissue were tested by fluorimetry assay. RESULTS: Compared with the controls, the pathologic score of small airways significantly increased in the CS exposed rats (20.3 +/- 14.7 vs. 53.7 +/- 11.5, P < 0.05). The Clara cell particles in cytoplasm decreased in the CS group (P < 0.05). The percentage of CC16-positive cells in bronchioles in the CS group (27.8 +/- 4.3 and 29.5 +/- 2.4 in terminal bronchioles and respiratory bronchioles, respectively) significantly decreased as compared with the control group (37.1 +/- 3.8 and 43.8 +/- 5.8 in terminal bronchioles and respiratory bronchioles, respectively) (P < 0.05). No significant difference was observed in GSH level ((181 +/- 26) nmol/L in the control group vs. (170 +/- 18) nmol/L in the CS group) between the two groups. After treatment with NAC, the pathologic score of small airways (24.1 +/- 17.5) decreased (P < 0.05). Clara cell particles in cytoplasm of Clara cells increased and GSH level in plasma ((213 +/- 40) nmol/L vs. (170 +/- 18) nmol/L in the CS group) increased too (P < 0.05), while the increase in the proportions of CC16 positive cells in bronchioles (30.1 +/- 6.4 and 34.3 +/- 6.3 in terminal bronchioles and respiratory bronchioles, respectively) did not reach the statistical significance (P > 0.05). No significant difference was found in the expression of CC16 mRNA among the three groups. Correlation analysis indicated that the percentage of CC16-positive cells in bronchioles negatively correlated with the pathologic score of small airways (r = -0.592, P < 0.05), but not with GSH level. CONCLUSIONS: One-week CS exposure decreased the number of Clara cells and the expression of CC16 in bronchioles in rats. NAC might provide protection of the Clara cells from oxidative damage and possibly through the elevation of the synthesis and secretion of CC16. These data indicate that NAC decreases airway inflammation induced by CS via induction of CC16.

Effects of sulfur dioxide on hypoxic pulmonary vascular structural remodeling.

Hypoxic pulmonary hypertension is a pathophysiological process important in the development of various cardiopulmonary diseases. Recently, we found that sulfur dioxide could be produced endogenously by pulmonary vessels, and that it showed vascular regulatory capabilities. In this paper, we examined the role of sulfur dioxide in hypoxic pulmonary vascular structural remodeling (HPVSR). A total of 48 Wistar rats were divided into six groups. Rats in the hypoxic group, hypoxic+sulfur dioxide group, and hypoxic+hydroxamate group were left under hypoxic conditions, whereas the control group, control+sulfur dioxide group, and control+hydroxamate group rats were left in room air. For each group, we measured the pulmonary arterial pressure, sulfur dioxide content in plasma and lung tissue, glutamate oxaloacetate transaminase 1 and 2 mRNAs, micro- and ultra-structural changes in pulmonary arteries, proliferation of pulmonary smooth muscle cells, vascular collagen metabolism, pulmonary endothelial cell inflammatory response, and pulmonary vascular endothelin-1 production in the rats. In hypoxic rats, the content of sulfur dioxide in plasma and lung tissue decreased significantly in comparison with those in the control groups, and significant pulmonary hypertension, pulmonary vascular structural remodeling, and increased vascular inflammatory response were also observed in hypoxic rats. Sulfur dioxide donor significantly downregulated Raf-1, mitogen-activated protein kinase kinase-1 (MEK-1) and p-ERK/ERK, and inhibited pulmonary vascular smooth muscle cell proliferation, collagen remodeling and pulmonary vascular endothelial cell nuclear factor-kappaB (NF-kappaB), and intercellular adhesion molecule 1 (ICAM-1) expressions. It also prevented pulmonary hypertension and pulmonary vascular structural remodeling in association with the upregulated sulfur dioxide/glutamate oxaloacetate transaminase pathway. Hydroxamate, however, advanced pulmonary hypertension, pulmonary vascular structural remodeling, and inflammatory response of the pulmonary artery in association with a downregulated sulfur dioxide/glutamate oxaloacetate transaminase pathway. The results suggested that sulfur dioxide markedly inhibited Raf-1, MEK-1, and the phosphorylation of extracellular signal-regulated kinase (ERK), and then inhibited pulmonary arterial smooth muscle cell (PASMC) proliferation induced by hypoxia. The downregulated sulfur dioxide/glutamate oxaloacetate transaminase pathway may be involved in the mechanisms responsible for pulmonary hypertension and pulmonary vascular structural remodeling.

Hydrogen sulfide regulates cardiac function and structure in adriamycin-induced cardiomyopathy.

BACKGROUND: The present study was designed to investigate if hydrogen sulfide (H2S), a novel gasotransmitter, might have a regulatory effect on cardiac function and structure, as well as oxidative stress, in adriamycin (ADR)-induced cardiomyopathy. METHODS AND RESULTS: Hemodynamic measurements, histopathological examination and stereological ultrastructural analysis of mitochondria in ADR-treated rats showed characteristics of cardiomyopathy with remarkable greater size and smaller number of cardiomyocytic mitochondria and a significantly low H2S content in plasma and myocardium, but increased levels of thiobarbituric acid reactive substance (TBARs) and decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in plasma and myocardium compared with controls (P<0.01). However, administration of the H2S donor, NaHS, markedly improved cardiac function, as demonstrated by elevated left ventricular developed pressure (+/-LVdp/dtmax; P<0.01) with ameliorated morphological alterations in the myocardium. Myocardial TBARs content decreased, whereas the activities of SOD and GSH-Px increased (P<0.01 and P<0.05, respectively). CONCLUSIONS: Downregulation of endogenously-generated H2S is probably involved in the pathogenesis of ADR-induced cardiomyopathy, whereby H2S reduces lipid peroxidation, increases antioxidation, and inhibits oxidative stress injury.

Role of hydrogen sulfide in the development of atherosclerotic lesions in apolipoprotein E knockout mice.

OBJECTIVE: We explored the effect of hydrogen sulfide (H(2)S) on atherosclerotic progression, particularly on intracellular adhesion molecule-1 (ICAM-1) in apolipoprotein-E knockout (apoE(-/-)) mice and human umbilical vein endothelial cells (HUVECs). METHODS AND RESULTS: ApoE(-/-) mice were treated with sodium hydrosulfide (NaHS) or DL-propargylglycine (PPG); HUVECs were pretreated with NaHS. Compared with control mice, apoE(-/-) mice showed decreased plasma H(2)S level and aortic H(2)S production but increased plasma ICAM-1 and aortic ICAM-1 protein and mRNA. Compared with apoE(-/-) mice, apoE(-/-)+NaHS mice showed increased plasma H(2)S level, but decreased size of atherosclerotic plaque and plasma and aortic ICAM-1 levels, whereas apoE(-/-)+PPG mice showed decreased plasma H(2)S level but enlarged plaque size and increased plasma and aortic ICAM-1 levels. NaHS suppressed ICAM-1 expression in tumor necrosis factor (TNF)-alpha-treated HUVECs. NaHS inhibited IkappaB degradation and NF-kappaB nuclear translocation in HUVECs treated with TNF-alpha. CONCLUSIONS: The vascular CSE/H(2)S pathway was disturbed in apoE(-/-) mice. H(2)S exerted an antiatherogenic effect and inhibited ICAM-1 expression in apoE(-/-) mice. H(2)S inhibited ICAM-1 expression in TNF-alpha-induced HUVECs via the NF-kappaB pathway.

[Establishment of Mongolian gerbil model of long-term Helicobacter pylori infection].

OBJECTIVE: To establish a model of long-term infection with Helicobacter pylori (Hp) in Mongolian gerbil (Meriones unguiculatus), and to investigate if Hp combined with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) has a synergistic effect to induce gastric mucosa injury. To investigate pathological changes of gastric mucosa during long-term Hp infection in Mongolian gerbil model. METHODS: 90 healthy male Mongolian gerbils were randomly divided into 4 groups: Hp group (n = 24) undergoing gastric perfusion of Hp suspension of the line NCTC11637 in brain-heart infusion (BHI) 10(8)-10(9) CFU/ml once a day for 10 days and then gastric perfusion of 1 ml normal saline (NS) once a day for 10 days since the 4th week after Hp perfusion, Hp + MNNG group (n = 24) undergoing gastric perfusion of Hp solution once a day for 10 days and then MNNG 1 ml (2 mg/ml) once a day for 10 days, MNNG group (n = 20) undergoing gastric perfusion of BHI once a day for 10 days and then gastric perfusion of MNNC once a day for 10 day since the 4th week after BHI perfusion, and control group (n = 22) undergoing gastric perfusion of BHI once a day for 10 days and then gastric perfusion of NS again once a day for 10 day since the 4th week after the BHI perfusion. 4 and 8 weeks 1 gerbil from the control group and 2 gerbils from the Hp and Hp + MNNG groups each were killed to observe the pathological changes and Hp colonization by liquid-based urease test and Warthin-Starry silver staining. 20 and 40 weeks after the Hp inoculation 10 gerbils from each group were killed to observe the pathology of the gastric mucosa. RESULTS: (1) A Mongolian gerbil model of long-term Hp infection was successfully established. (2) Hp induced the process progressing from normal gastric mucosa --> chronic atrophic gastritis --> intestinal metaplasia --> dysplasia. Until 40 weeks after Hp infection, the gastric mucosa of the control group remained normal. Twenty weeks after Hp infection 3 gerbils in the Hp group and 1 gerbil in the Hp + MNNC group showed glandular atrophy and intestinal metaplasia respectively, and 40 weeks after infection, glandular atrophy, intestinal metaplasia, and dysplasia at different degrees in the gastric mucosa were seen in the three experimental groups. The pathological changes of the Hp + MNNG group were the most severe. The incidence rates of precancerous lesions of the Hp + MNNG group were significantly higher than those of the other groups, but no gastric carcinoma was found in the experimental animals. CONCLUSION: Hp colonizes stably in the glandular gastric mucosa of Mongolian gerbils. The histological changes after infection are similar to those of the Hp infected human being. Hp and MNNG both cause the injury of gastric mucosa. With synergistic effect, the two pathogenic agents attack the gastric mucosa, they cause more severe injury.

The regulatory effect of endogenous hydrogen sulfide on pulmonary vascular structure and gasotransmitters in rats with high pulmonary blood flow.

The study aimed to explore the regulatory effect of endogenous hydrogen sulfide (H(2)S), a novel gasotransmitter, on pulmonary vascular structure and gasotransmitters in rats with high pulmonary blood flow. Thirty-two Sprague-Dawley rats were randomly divided into a sham group, shunt group, sham+PPG (propargylglycine, an inhibitor of cystathionine-gamma-lyase) group and shunt+PPG group. Rats in the shunt and shunt+PPG groups underwent abdominal aorta-inferior vena cava shunting. Rats in the shunt+PPG and sham+PPG groups were intraperitoneally injected with PPG. After 4 weeks of shunting, mean pulmonary artery pressure (MPAP) and pulmonary vascular structural remodeling (PVSR) were evaluated. H(2)S, nitric oxide (NO) and carbon monoxide (CO) contents were measured in lung tissues. Meanwhile, nitric oxide synthase (eNOS), heme oxygenase (HO-1) and proliferative cell nuclear antigen (PCNA) protein expressions and ERK activation were evaluated. After 4 weeks of shunting, rats showed PVSR with increased lung tissue H(2)S and NO content but decreased CO content. After the PPG treatment, MPAP further increased and PVSR was aggravated. Meanwhile, PCNA expression and ERK activation were augmented with decreased lung tissue CO and HO-1 protein production but increased lung tissue NO production and eNOS expression. H(2)S exerted a protective effect on PVSR, and the inhibition of the NO/NOS pathway and the augmentation of the CO/HO pathway might be involved in the mechanisms by which H(2)S regulates PVSR in rats with high pulmonary flow.

[The pathological characters and its clinical significance of internal hemorrhoids].

OBJECTIVE: To investigate the pathological characters and the corresponding clinical significance of internal hemorrhoids tissues. METHODS: Normal anal cushion and internal haemorrhoids tissue samples were obtained after stapled haemorrhoidectomy procedure from 24 grade III hemorrhoidal patients. The macroscopically normal cushions served as own controls and the normal cushions from a patient without a history of haemorrhoids as quality control. Routine Hematoxylin-Eosin and orcein were performed for elastic fibers. RESULTS: Compared with the corresponding normal anal cushions, the subepithelial vessels especially the cavernous vessels of the hemorrhoidal tissues showed obvious structural impair, retrograde changes, and the internal elastic lamina were ruptured and discontinuous. In addition, thrombosis and subsequent ischemic changes were observed. The Trietz's muscle and the fibro-elastic tissues showed hypertrophy, distortion, rupture and tortility. Obvious mucosal injury was observed in the mucous of hemorrhoidal tissues. Venous dilatation was infrequent in the hemorrhoidal tissues. CONCLUSIONS: The anal cushions of hemorrhoids disease patients show significant pathological changes. The pathological changes include structural impair, retrograde changes of the cavernous vessels and the hypertrophy, distortion, rupture and tortility of the Trietz's muscle and the fibroelastic tissues, and mucosal injury of the mucous membranes. These pathological changes are the basis of pathogenesis and development of hemorrhoids.