Multiple organ dysfunction after mitral valve replacement in a patient with systemic lupus erythematosus complicated by Libman-Sacks endocarditis: a case report and literature review.

This case report describes a 47-year-old woman with systemic lupus erythematosus (SLE) complicated by Libman-Sacks endocarditis (LSE) who developed multiple organ dysfunction after mitral valve replacement surgery. The patient presented with a 5-day history of cough, sputum, and fever. Transthoracic echocardiography showed significant vegetations on the mitral valve. Biopsy was performed, and the pathological diagnosis was SLE complicated by LSE. After the mitral valve replacement surgery, the patient developed clinical manifestations of hepatic and renal dysfunction, cardiopulmonary failure, oliguria, and shock. The clinical symptoms significantly improved after administration of mechanical ventilation, continuous renal replacement therapy, plasma exchange, anti-inflammatory and anti-infection treatments, immunomodulatory and immunosuppressive therapies, and low-molecular-weight heparin anticoagulation. Multiple organ dysfunction after mitral valve replacement in patients with SLE complicated by LSE has rarely been reported. This report discusses the clinical manifestations, pathogenesis, and treatment of this severe complication. We hope the sharing of our experience in this case will provide a clinical basis for the treatment of severe multiple organ dysfunction after mitral valve replacement in patients with SLE complicated by LSE.

Epidemiological and clinical characteristics of COVID-19 patients in Hengyang, Hunan Province, China.

BACKGROUND: In December 2019, an ongoing outbreak of coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China. The characteristics of COVID-19 patients treated in local hospitals in Wuhan are not fully representative of patients outside Wuhan. Therefore, it is highly essential to analyze the epidemiological and clinical characteristics of COVID-19 in areas outside Wuhan or Hubei Province. To date, a limited number of studies have concentrated on the epidemiological and clinical characteristics of COVID-19 patients with different genders, clinical classification, and with or without basic diseases. AIM: To study the epidemiological and clinical characteristics of COVID-19 patients in Hengyang (China) and provide a reliable reference for the prevention and control of COVID-19. METHODS: From January 16 to March 2, 2020, a total of 48 confirmed cases of COVID-19 were reported in Hengyang, and those cases were included in this study. The diagnostic criteria, clinical classification, and discharge standard related to COVID-19 were in line with the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7) released by National Health Commission and National Administration of Traditional Chinese Medicine. The presence of SARS-CoV-2 in pharyngeal swab specimens was detected by quantitative reverse transcription polymerase chain reaction. All the data were imported into the excel worksheet and statistically analyzed by using SPSS 25.0 software. RESULTS: A total of 48 cases of COVID-19 were collected, of which 1 was mild, 38 were moderate, and 9 were severe. It was unveiled that there were 31 (64.6%) male patients and 17 (35.4%) female patients, with a female-to-male ratio of 1.82:1. The range of age of patients with COVID-19 was dominantly 30-49 years old [25 (52.1%) of 48], followed by those aged over 60 years old [11 (22.9%)]. Besides, 29.2% (14 of 48) of patients had basic diseases, and 57.2% (8 of 14) of patients with basic diseases were aged over 60 years old. The occupations of 48 COVID-19 patients were mainly farmers working in agricultural production [15 (31.5%) of 48], rural migrant workers from Hengyang to Wuhan [15 (31.5%)], and service workers operating in the service sector [8 (16.7%)]. The mean latent period was 6.86 ± 3.57 d, and the median was 7 [interquartile range (IQR): 4-9] d. The mean time from onset of symptoms to the first physician visit was 3.38 ± 2.98 (95%CI: 2.58-9.18) d, with a median of 2 (IQR: 1-5) d, and the mean time from hospital admission to confirmed diagnosis was 2.29 ± 2.11 (95%CI: 1.18-6.42) d, with a median of 2 (IQR: 1-3) d. The main symptoms were fever [43 (89.6%) of 48], cough and expectoration [41 (85.4%)], fatigue [22 (45.8%)], and chills [22 (45.8%)]. Other symptoms included poor appetite [13 (27.1%)], sore throat [9 (18.8%)], dyspnea [9 (18.8%)], diarrhea [7 (14.6%)], dizziness [5 (10.4%)], headache [5 (10.4%)], muscle pain [5 (10.4%)], nausea and vomiting [4 (8.3%)], hemoptysis [4 (8.3%)], and runny nose [1 (2.1%)]. The numbers of peripheral blood leukocytes, lymphocytes, and eosinophils were significantly reduced in the majority of the patients. The levels of C-reactive protein, fibrinogen, blood glucose, lactate dehydrogenase, D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (γ-GT), myoglobin (MB), and creatine kinase (CK) were increased in 64.6%, 44.7%, 43.2%, 37.0%, 29.5%, 22.9%,20.8%, 21.6%, 13.6%, and 12.8% of patients, respectively. The incidence of ALT elevation in male patients was remarkably higher than that in females (P < 0.01), while the incidences of AST, CK, and blood glucose elevations in severe patients were remarkably higher than those in moderate patients (P < 0.05, respectively). Except for the mild patients, chest computed tomography showed characteristic pulmonary lesions. All the patients received antiviral drugs, 38 (79.2%) accepted traditional Chinese medicine, and 2 (4.2%) received treatment of human umbilical-cord mesenchymal stem cells. On March 2, 2020, 48 patients with COVID-19 were all cured and discharged. CONCLUSION: Based on our results, patients with COVID-19 often have multiple organ dysfunction or damage. The incidences of ALT elevation in males, and AST, CK, and blood glucose elevations in severe patients are remarkably higher.

Integrative Analysis of Siglec-15 mRNA in Human Cancers Based on Data Mining.

Objective: Cancer is expected to be the leading cause of death worldwide within the 21st century and is the single most important obstacle to extending life expectancy. Unfortunately, the most effective approach to combating cancers remains a complex and unsolved problem. Siglec-15 is a member of the Siglec family and plays a conserved regulatory role in the immune system of vertebrates. Previous studies on Siglec-15 have focused on its function in osteoclast regulation. The purpose of this study was to explore the significance of Siglec-15 mRNA in human cancer mainly based on information obtained from online databases. Method: Data were collected from several online databases. Serial analysis of gene expression (SAGE) and Virtual Northern, UALCAN Database Analysis, Catalog of Somatic Mutations in Cancer (COSMIC) analysis, the cBio cancer genomics portal, Cancer Regulome tools and data, Kaplan-Meier Plotter Analysis and the UCSC Xena website were used to analyze the data. Results: Compared with normal tissues, Siglec-15 up-regulation was widely observed in tuomrs. Differences in Siglec-15 expression were associated with different prognoses. Siglec-15 mutations are widely observed in tumors and interact with different genes in different cancer types. Conclusion: Siglec-15 is a potential target for the expansion of cancer immunotherapy.

Can serum glypican-3 be a biomarker for effective diagnosis of hepatocellular carcinoma? A meta-analysis of the literature.

OBJECTIVE: This review is to evaluate the diagnostic value of serum GPC3 for hepatocellular carcinoma (HCC) due to conflicting results reported. METHODS: NCBI PubMed and Embase were comprehensively searched for studies that have used serum GPC3 level as a diagnostic index for HCC. The quality of the included studies was assessed. Subgroup analyses were conducted to evaluate the sensitivity and specificity of GPC3 as a HCC marker. Statistical analysis was performed with the software STATA version 12.0. RESULTS: A total of 22 studies were included. The qualities of included studies were relatively poor. Among them, 18 studies have shown that serum GPC3 is a specific biomarker for HCC, and the pooled sensitivity and specificity of these studies were 69 and 93%, respectively. The other 4 studies have reported conflicting results, which were not caused by races, infection status of HBV and HCV, or assay reagents but due to one common experimental design of enrolling liver cirrhosis patients as control subjects. CONCLUSIONS: This meta-analysis indicates that serum GPC3 is elevated in HCC patients compared with healthy individuals, but more studies are needed to evaluate its effectiveness to differentially diagnose HCC and liver cirrhosis.

Cardiovascular protection and antioxidant activity of the extracts from the mycelia of Cordyceps sinensis act partially via adenosine receptors.

Mycelia of cultured Cordyceps sinensis (CS) is one of the most common substitutes for natural CS and was approved for arrhythmia in China. However, the role of CS in ameliorating injury during ischemia-reperfusion (I/R) is still unclear. We examined effects of extracts from CS on I/R and investigated the possible mechanisms. Post-ischemic coronary perfusion pressure, ventricular function, and coronary flow were measured using the Langendorff mouse heart model. Oxidative stress of cardiac homogenates was performed using an ELISA. Our results indicate that CS affords cardioprotection possibly through enhanced adenosine receptor activation. Cardioprotection was demonstrated by reduced post-ischemic diastolic dysfunction and improved recovery of pressure development and coronary flow. Treatment with CS largely abrogates oxidative stress and damage in glucose- or pyruvate-perfused hearts. Importantly, observed reductions in oxidative stress [glutathione disulfide (GSSG)]/[GSSG + glutathione] and [malondialdehyde (MDA)]/[superoxide dismutase + MDA] ratios as well as the resultant damage upon CS treatment correlate with functional markers of post-ischemic myocardial outcome. These effects of CS were partially blocked by 8-ρ-sulfophenyltheophylline, an adenosine receptor antagonist. Our results demonstrate a suppressive role of CS in ischemic contracture. Meanwhile, the results also suggest pre-ischemic adenosine receptor activation may be involved in reducing contracture in hearts pretreated with CS.

Ascorbic acid uptaken by sodium-dependent vitamin C transporter 2 induces ßhCG expression through Sp1 and TFAP2A transcription factors in human choriocarcinoma cells.

CONTEXT: Vitamin C [ascorbic acid (AA)] is transported by sodium-dependent vitamin C transporters (SVCT) 1 and 2, and our previous studies show AA induces a dramatic production of steroid hormones in human choriocarcinoma cells. However, whether AA induces the production of placental polypeptide hormones remains unknown. Here we investigated the mechanisms governing AA-induced ß-human chorionic gonadotropin (hCG) expression. METHODS: Frozen sections from human term placentas were used for immunostaining of SVCT, and ßhCG mRNA expression and its production in primary human placental cytotrophoblasts and JEG-3 cells were examined by quantitative RT-PCR and ELISA, respectively. Knockdown of SVCT2, transcription factor activating enhancer-binding protein 2α (TFAP2A), or specificity protein-1 (Sp1) expression was achieved by retrovirus-mediated short hairpin RNA, and the transcriptional factors responsible for AA-induced ßhCG expression was identified by reporter constructs. RESULTS: Both SVCT1 and SVCT2 are expressed in human term placentas. SVCT2 is predominantly localized in the syncytial layer, whereas SVCT1 is predominantly distributed in the villous core. AA dramatically induces ßhCG mRNA expression and its production in JEG-3 cells and primary human cytotrophoblasts, and knockdown of SVCT2 expression in JEG-3 cells significantly decreases AA-induced ßhCG expression. Data from ßhCG5 construct and its deletion mutants further indicate that AA induces ßhCG5 transactivation through Sp1 and TFAP2A transcriptional factors, and silence of Sp1 and/or TFAP2A expression significantly decreased AA-induced ßhCG5 reporter activity and ßhCG expression as well. CONCLUSIONS: The present study revealed the novel effects of AA on polypeptide hormone, ßhCG, production and the potential mechanisms governing AA-induced ßhCG expression, suggesting the potentially indispensable roles of AA in placental endocrine and pregnant maintenance.

Simvastatin delivery via inhalation attenuates airway inflammation in a murine model of asthma.

The dose-response of the pleiotropic effects of statins on airway inflammation has not yet been established and may differ from that of their cholesterol-lowering effects. High oral doses of statins may have adverse effects, and it may be possible to overcome the side effects and low clinical efficacy by administering statins via inhalation. In this study, we hypothesize that simvastatin is a potential anti-inflammatory drug with biological and pharmacokinetic properties suitable for delivery by the inhaled route. Mice were immunized with ovalbumin (OVA) and then challenged with aerosol OVA. Simvastatin was locally delivered by inhalation (i.h.) and intratracheal injection (i.t.) or systematically delivered by intraperitoneal injection (i.p.) and gavage (i.g.) during the OVA challenge. In a mouse model of asthma, i.h. simvastatin significantly and dose-dependently attenuated airway inflammation, remodeling and hyperresponsiveness in a RhoA-dependent pathway. Upon comparing the pharmacodynamics, i.h. simvastatin had a more potent effect than that of i.g. and i.p. simvastatin, and the i.h. or i.t. delivery routes led to a higher drug concentration in local lung tissue and a lower drug concentration in the plasma than that obtained by the i.g. These results suggest that simvastatin is a potential anti-inflammatory drug for airway inflammatory diseases with properties suitable for delivery by inhalation, which will probably reduce the side effects and increase clinical efficacy.

Oral administration of allergen extracts from mugwort pollen desensitizes specific allergen-induced allergy in mice.

Clinically, sublingual immunotherapy (SLIT) using allergen extracts effectively alleviates the symptoms of allergic rhinitis and asthma. We hypothesized that oral administration of a high-dose of allergen extracts imitates SLIT, which may prevent IgE-related responses in allergic diseases. In the present study, we investigated the effects of oral administration of allergen extracts from mugwort pollen (MP) on allergen-induced inflammation and airway hyperresponsiveness (AHR) in an allergic mouse model. After administration of MPdrop containing Art v 1 and Art v 4 extracts derived from MP specifically in MP-sensitized mice, the effects of MPdrop on AHR, inflammatory cell accumulation, cytokine production in the bronchoalveolar lavage fluid and lung tissue, and serum IgE and IgG levels were investigated. The results indicated that MPdrop not only prevented the AHR in response to methacholine in a dose-dependent manner but also significantly reduced the total serum and allergen-specific IgE levels. All of the maximal effects were achieved at a dose of 100µg/(kgd) and were comparable to the effects of dexamethasone at a dose of 0.5mg/(kgd). Furthermore, oral administration of MPdrop dose-dependently elevated allergen-specific serum IgG2a levels, reduced total and allergen-specific IgE levels and normalized the imbalance between the Th1 cytokine IL-12 and Th2 cytokines IL-4 and IL-5. Finally, oral administration of MPdrop significantly reduced goblet cell hyperplasia and eosinophilia in the MP-sensitized allergic mouse model. These data suggest that MPdrop effectively improves specific allergen-induced inflammation and AHR in MP-sensitized and -challenged mice and provides the rationale for clinical use of MPdrop in the specific allergen-induced asthma.

Cyptoporus polysaccharide prevents lipopolysaccharide-induced acute lung injury associated with down-regulating Toll-like receptor 2 expression.

AIM OF THE STUDY: To evaluate the effects and the possible mechanism of Cryptoporus polysaccharides (CP) extracted from fruiting body of Cryptoporus volvatus in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and mice. MATERIALS AND METHODS: Acute lung injury was induced by intratracheally instillation of LPS into lung in either rats or mice, assessing leukocyte numbers and myeloperoxidase activity in bronchoalveolar lavage fluid, as well as evaluating cytokines mRNA and protein expressions, and Toll-like receptor 2 (TLR(2)) and nuclear factor (NF)-κB mRNA levels in the lung tissues of mice. Vascular permeability and edema of lung in mice, and arterial blood gas in rats were also performed. RESULTS: In ALI, CP-treated mice and rats exhibited significantly reduced leukocyte invasion, myeloperoxidase activity, vascular permeability, edema of lung, as well as tumor necrosis factor-α and Interleukin-1ß mRNA and protein expressions in the lung tissues compared with vehicle-treated mice. TLR(2) and NF-κB mRNA levels of the lung tissues were decreased in CP-treated mice in response to LPS. And decline in arterial blood gas was recovered in CP-treated rats. CONCLUSIONS: Our results supported a protective role of CP in ALI and suggested that the reduction of the activation of TLR(2) and NF-κB signal pathway in lung injury may be relavant to the pretreatment of CP.

Inhibition of Rac activity alleviates lipopolysaccharide-induced acute pulmonary injury in mice.

BACKGROUND: Rac small GTPases play important roles in cytoskeleton and many cell functions including cell cycle, cell growth, cell adhesion and gene transcription. Here, we investigated the roles of Rac including Rac1 and Rac2 in lipopolysaccharide (LPS)-induced pulmonary injury. METHODS: After LPS was intratracheally instilled to lungs in mice, Rac, CDC42 and RhoA activation assay by pull-down and West blot, inflammatory cell infiltration assay by counting cell numbers and lung histological examination, pro-inflammatory mediator mRNA expression assay by quantitative RT-PCR, measurement of myeloperoxidase (MPO) activity, Evans Blue and albumin accumulation by spectrophotometry were performed to evaluate the roles of Rac in pulmonary injury by using its specific inhibitor, NSC23766. RESULTS: LPS challenge led to increases of both Rac1 and Rac2, but not CDC42 or RhoA activities in lungs, and intraperitoneal administration with NSC23766 inhibited both Rac1 and Rac2, but not CDC42 or RhoA activities. Treatment with NSC23766 at 1 or 3mg/kg not only reduced the inflammatory cells infiltration and MPO activities, but also inhibited pro-inflammatory mediators, tumor necrosis factor-α and interleukin-1ß, mRNA expression. Moreover, in vitro neutrophil migration assay and in vivo microvascular permeability assay indicated that NSC23766 not only inhibited neutrophil transwell migration toward a chemoattractant, fMLP, but also reduced Evans Blue and albumin accumulation in LPS-challenged lungs. LPS activated both Rac1 and Rac2, but not CDC42 or RhoA activities in lungs, and specific inhibition of Rac activities by NSC23766 effectively alleviated LPS-induced injury. GENERAL SIGNIFICANCE: Rac could be a potential target for therapeutic intervention of pulmonary inflammation.

Anti-asthmatic effects of Perilla seed oil in the guinea pig in vitro and in vivo.

The aim of this study was to investigate the anti-asthmatic effects of Perilla seed oil in vitro and in vivo in sensitized guinea pigs. Aerosolized antigen caused an immediate bronchoconstriction. Perilla seed oil per os inhibited the increase in lung resistance and the decrease in dynamic lung compliance in a dose-dependent manner with an ED50 (95 % confidence interval, CI) of 1.10 (0.98 - 1.24) g/kg and 1.07 (0.94 - 1.22) g/kg, respectively. Infiltration of leukocytes, mononuclear cells, eosinophils and neutrophils induced by inhaling antigen was also inhibited by Perilla seed oil in a dose-dependent manner with an ED50 (95 % CI) of 1.00 (0.86 - 1.15), 1.24 (1.10 - 1.38), 0.63 (0.51 - 0.77) and 0.61 (0.38 - 0.98) g/kg, respectively. Perilla seed oil (5 - 500 microg/mL) inhibited the slow reaction substance of anaphylaxis (SRS-A) release induced by antigen challenge in lung tissue of sensitized guinea pigs. It also inhibited calcium ionophore (A(23187))-induced leukotriene (LT) D4 release from the lung tissue of non-sensitized guinea pigs in a concentration-dependent manner with an IC50 (95 % CI) of 50 (36 - 69) microg/mL. These results indicate that Perilla seed oil may improve lung function in asthma by controlling eicosanoid production and suppressing LT generation.

[The expression of TLR4 in rat acute lung injury induced by lipopolysaccharide and the influence of Eucalyptus globulus oil].

OBJECTIVE: To observe the distribution of toll-like receptor 4 (TLR4) in rats' respiratory tract. To study the influence of LPS and Eucalyptus globulus oil on the distribution of TMR4. METHOD: The Sprague-Dawley rats were intratracheally instilled with lipopolysaccharide (LPS,2 mg x kg(-1) per day) for two days to induce acute lung injury. The rats were sacrificed at 72 hours after LPS instillation. Lung morphology was studied. Leukocytes in Bronchoalveolar lavage fluid (BALF) were measured and TLR4 were detected by immunohistochemistry. RESULT: The result of immunohistochemistry showed that TLR4 distributed widely in common rats' respiratory tract. In the group of acute lung injury, the number of leucocyte in BALF was increased apparently, the inflammation in bronchus and bronchioles was more apparently than that of the control group in morphology. And the expression of TLR4 was reinforced in main bronchus and bronchioles. In the group of E. globules oil (300 mg x kg(-1)), the leucocyte number was decreased apparently in BALF, the inflammation was lightened and the expression of TLR4 decreased as compared with the group of models. CONCLUSION: The expression of TLR4 distributes widely in rats' respiratory tract. The stimulation of LPS can reinforce the expression of TLR4. The E. globules oil can reduce the increase of TLR4 induced by LPS in bronchioles.