The clinicopathological and prognostic significances of EZH2 expression in urological cancers: A meta­analysis and bioinformatics analysis.

The Drosophila zeste enhancer homolog 2 gene (enhancer of zeste homolog 2; EZH2) is an important member of the polycomb group (PcG) gene family, which maintains the homologous gene via chromosome modification during embryonic development. EZH2 is overexpressed in various tumors, is closely related to tumor formation and growth, and has a malignant phenotype that promotes tumor cell proliferation, proliferation and metastasis. In the present study, a meta- and bioinformatic analysis was performed using data from multiple online databases until August 30, 2022. EZH2 upregulation was found in kidney, bladder and prostate cancers. EZH2 expression was negatively related to TNM staging and pathological grade in kidney and prostate cancers (P<0.05), as well as invasion depth and pathological grade in bladder cancer. According to the KM-plotter database, EZH2 expression was inversely associated with poor overall survival in patients with kidney clear cell renal cell carcinoma (RCC) and papillary RCC and with favorable survival in bladder cancer. EZH2 expression was negatively related to relapse-free survival in kidney papillary RCC and bladder cancer but positively associated with kidney clear cell RCC. According to GEPIA and UALCAN databases, EZH2 expression was higher in tumor tissue than normal tissue. The TIMER database showed that EZH2 was closely associated with the proportion of seven immune cell infiltrates in kidney, bladder, and prostate cancers. High EZH2 expression may be a potential marker of tumorigenesis and metastasis in patients with urological cancers.

Research on Residual Stresses and Microstructures of Selective Laser Melted Ti6Al4V Treated by Thermal Vibration Stress Relief.

The efficient and cost-effective residual stress control method is of great significance for the application of additive manufacturing (AM) technology. In this work, thermal-vibration stress relief (TVSR) with different temperatures and dynamic stresses was performed on Ti6Al4V samples prepared by selective laser melting (SLM), the stress relief effects of TVSR and its influence on phase and microstructure were investigated and compared with thermal stress relief (TSR) and vibration stress relief (VSR), and the stress relief mechanisms of these methods are discussed. It was found that the residual stress relief rate can reach 86.76% after TVSR treatment at a temperature of 380 °C and a dynamic stress of 400 MPa, which increased by 63.63% compared with VSR under the same dynamic stress. The efficiency is increased by 76% compared with TSR at 580 °C and the residual stress relief rate is almost the same. After TVSR, VSR and TSR treatments, the grain morphology, size and phase content of samples were basically unchanged, and low-angle grain boundaries (LAGBs) were increased after TVSR and VSR treatments and decreased after TSR treatment. The results confirm that the TVSR method has the ability to control the residual stress of selective laser melted Ti6Al4V with low time and cost consumption, and are helpful for engineering applications of TVSR.

Preparation and Process Parameter Optimization of Continuous Carbon Fiber-Reinforced Polycarbonate Prepreg Filament.

Continuous fiber-reinforced composite 3D printing (CFRC 3DP) has become a hot topic of interest for many experts and scholars. Continuous fiber-reinforced prepreg filament (CFRPF) for printing needs to be prepared in advance. In this paper, on the basis of the resin fusion impregnation theory, a fabrication device was designed for continuous carbon fiber-reinforced polycarbonate prepreg filament (CCFRPF). Then, according to the orthogonal test and the TOPSIS entropy weight optimization theory, the optimization method for CFRPF/PC preparation process parameters was proposed, and the relationship between the preparation process parameters and the performance indexes was discussed. The results show that when preparing CCFRPF/PC, the weight of diameter performance index is the largest, about 0.75. The optimal combination of process parameters for CCFRPF/PC is, respectively, 285 °C for the outlet mold temperature, 305 °C for the impregnation mold temperature, and 1 m/min for the winding speed. In this case, the diameter, roundness, minimum curvature radius and tensile strength of 0.375 mm, 29.4 µm, 9.775 mm and 1298 MPa were achieved, respectively.

Research on the Simulation Model of Continuous Fiber-Reinforced Composites Printing Track.

The rapid development of additive manufacturing technology (AM) is revolutionizing the traditional continuous fiber-reinforced polymer (CFRP) manufacturing process. The combination of FDM technology and CFRP technology gave birth to continuous fiber reinforced thermoplastic composites (CFRTPC) 3D printing technology. Parts with complex structure and excellent performance can be fabricated by this technology. However, the current research on CFRTPC printing mainly focuses on printing equipment, materials, and the improvement of mechanical properties. In this paper, the CFRTPC 3D printing track errors are investigated during the printing process, and it is found that the polytetrafluoroetylene (PTFE) tube in the nozzle of the printer head is often blocked. Through detailed analysis, a line-following mathematical model reflecting the deviations of the CFRTPC printing track is established. According to the characteristics of the fiber and its track during actual laying, a modified line-following model, without the minimum curvature point, is further proposed. Based on this model, the actual printing track for the theoretical path is simulated, the process tests are carried out on the printing track at different corner angles, and the relevant rules between the parameters of the model and different corner angles are obtained. The mathematical model is verified by experiments, and the clogging problem of the printer head caused by the fiber track error is solved, which provides theoretical support for the rational design of the fiber track in CFRTPC printing.

Effects of the working experience, educational background, professional titles, and hospital grades of intensive care unit doctors on clinical glucocorticoid use in acute respiratory distress syndrome.

ABSTRACT: Although glucocorticoids are commonly used for patients with acute respiratory distress syndrome in the intensive care unit, the exact attitudes of different intensive care unit (ICU) doctors about glucocorticoid usage are largely unknown. Herein, we investigated the practice of glucocorticoid application for acute respiratory distress syndrome (ARDS) by ICU doctors in China. Questionnaires were developed and sent to ICU doctors at 45 hospitals to perform statistics and analysis. ICU doctors with more working experience and professional titles had more knowledge of ARDS. Glucocorticoids were more likely to be used for ARDS caused by chemical inhalation. Doctors with longer working experience, better educational background, and higher professional titles used fewer glucocorticoids. In addition, 97.2%of the doctors considered using methylprednisolone or hydrocortisone first, 50.9% used glucocorticoids within 24hours of onset, and 37.1% insisted that steroid therapy should last 3 to 5days. Although ICU doctors with more working experience and professional titles have a better understanding of glucocorticoid use in ARDS, the majority of clinical practices and attitudes are similar among different doctors regardless of working experience, educational background, professional titles, or hospital grades.

Risk Factors for and Clinical Outcomes of Polymicrobial Acinetobacter baumannii Bloodstream Infections.

Background: Although the clinical features of Acinetobacter baumannii bloodstream infection are well described, the specific clinical characteristics of polymicrobial Acinetobacter baumannii bloodstream infection have been rarely reported. The objective of this study was to examine the risk factors for and clinical outcomes of polymicrobial Acinetobacter baumannii bloodstream infection. Methods: A retrospective observational study was performed from January 2013 to December 2018 in a tertiary hospital. All patients with Acinetobacter baumannii bloodstream infection were enrolled, and the data were collected from the electronic medical records. Results: A total of 594 patients were included, 21% (126/594) of whom had polymicrobial infection. The most common copathogen was Klebsiella pneumoniae (20.81%), followed by Pseudomonas aeruginosa (16.78%) and Enterococcus faecium (12.08%). Compared with monomicrobial Acinetobacter baumannii bloodstream infection, polymicrobial Acinetobacter baumannii bloodstream infection mostly originated from the skin and soft tissue (28.6% vs. 10.5%, p < 0.001). Multivariate analysis revealed that burn injury was independently associated with polymicrobial Acinetobacter baumannii bloodstream infection (adjusted odds ratio, 3.569; 95% confidence interval, 1.954-6.516). Patients with polymicrobial Acinetobacter baumannii bloodstream infection were more likely to have a longer hospital length of stay [40 (21, 68) vs. 27 (16, 45), p < 0.001] and more hospitalization days after bloodstream infection than those with monomicrobial Acinetobacter baumannii bloodstream infection [22 (8, 50) vs. 13 (4, 28), p < 0.001]. However, no significant difference in mortality was observed between the two groups. Conclusions: Approximately one-fifth of Acinetobacter baumannii bloodstream infections were polymicrobial in this cohort. The main sources were skin and soft tissue infections, and burn injury was the only independent risk factor. Although mortality did not differ between the groups, considering the limitations of the study, further studies are required to assess the impact of polymicrobial (vs. monomicrobial) Acinetobacter baumannii bloodstream infection on outcomes.

Optimization of the Forming Method on Torsion Defect in Cold-Roll Forming of Z Section Steel.

The knurling design is the basis of cold-roll forming, which is related to the subsequent roll design. It is also the basis to determine the roll pass. As a typical cross-section, Z-shaped steel is widely used in automobile, household appliance manufacturing, and building structure installation. However, torsion defects often occur in the cold-roll forming of Z-shaped steel, resulting in unqualified products that are unusable. The web deflection angle is a typical factor to affect the torsion defects in the cold-roll forming of Z-shaped steel. Therefore, it is necessary to discuss the influence of web deflection on the torsion of the Z-shaped steel. The web deflection angle optimized is determined by the result. According to the theoretical calculation, the best antitorsion angle is 32°, and the conjecture is proved by experiments. Also, we obtain the forming method optimized with the least torsion. This study could provide some guidance for the design of the process flow of cold-formed Z-beam.

Clinical characteristics, risk factors and outcomes of mixed Candida albicans/bacterial bloodstream infections.

PURPOSE: The purpose of this study was to explore the clinical features, risk factors, and outcomes of mixed Candida albicans/bacterial bloodstream infections (mixed-CA/B-BSIs) compared with monomicrobial Candida albicans bloodstream infection (mono-CA-BSI) in adult patients in China. METHODS: All hospitalized adults with Candida albicans bloodstream infection (CA-BSI) were recruited for this retrospective observational study from January 1, 2013, to December 31, 2018. RESULTS: Of the 117 patients with CA-BSI, 24 patients (20.5%) had mixed-CA/B-BSIs. The most common copathogens were coagulase-negative Staphylococcus (CNS) (24.0%), followed by Klebsiella pneumoniae (20.0%) and Staphylococcus aureus (16.0%). In the multivariable analysis, a prior ICU stay > 2 days (adjusted odds ratio [OR], 7.445; 95% confidence interval [CI], 1.152-48.132) was an independent risk factor for mixed-CA/B-BSIs. Compared with patients with mono-CA-BSI, patients with mixed-CA/B-BSIs had a prolonged length of mechanical ventilation [17.5 (4.5, 34.8) vs. 3.0 (0.0, 24.5), p = 0.019] and prolonged length of ICU stay [22.0 (14.3, 42.2) vs. 8.0 (0.0, 31.5), p = 0.010]; however, mortality was not significantly different. CONCLUSIONS: There was a high rate of mixed-CA/B-BSIs cases among CA-BSI cases, and CNS was the predominant coexisting species. A prior ICU stay > 2 days was an independent risk factor for mixed -CA/B-BSIs. Although there was no difference in mortality, the outcomes of patients with mixed -CA/B-BSIs, including prolonged length of mechanical ventilation and prolonged length of ICU stay, were worse than those with mono-CA-BSI; this deserves further attention from clinicians.

Clinical Characteristics And Risk Factors In Mixed-Enterococcal Bloodstream Infections.

PURPOSE: Although the enterococcal bloodstream infections (EBSI) are often observed in clinic, the mixed-EBSI are few reported. The aim of this study was to investigate the clinical characteristics and risk factors of mixed-EBSI in comparison with monomicrobial EBSI (mono-EBSI). METHODS: A single-center retrospective observational study was performed between Jan 1, 2013 and Dec 31, 2018 in a tertiary hospital. All patients with EBSI were enrolled, and their data were collected by reviewing electronic medical records. RESULTS: A total of 451 patients with EBSI were enrolled including 157 cases (34.8%) with mixed-EBSI. The most common co-pathogens were Coagulase-negative Staphylococcus (26.86%), followed by Acinetobacter baumannii (23.43%) and Klebsiella pneumoniae (8.57%). In multivariable analysis, burn injury (adjusted odds ratio [aOR], 7.39; 95% confidence interval [CI], 2.69-20.28), and length of prior hospital stay (aOR, 1.01; 95% CI, 1.00-1.02) were associated with mixed-EBSI. Patients with mixed-EBSI developed with more proportion of septic shock (19% vs. 31.8%, p=0.002), prolonged length of intensive care unit (ICU) stay [9(0,25) vs. 15(2.5,36), p<0.001] and hospital stay [29(16,49) vs. 33(18.5,63), p=0.031]. The mortality was not significantly different between mixed-EBSI and mono-EBSI (p=0.219). CONCLUSION: A high rate of mixed-EBSI is among EBSI, and Acinetobacter baumannii is the second predominant co-existed species, except for Coagulase-negative Staphylococcus. Burn injury and length of prior hospital stay are independent risk factors for mixed-EBSI. Although the mortality is not different, patients with mixed-EBSI might have poor outcomes in comparison with mono-EBSI, which merits more attention by physicians in the future.

The efficacy and safety of azithromycin in asthma: A systematic review.

Azithromycin is a potential therapeutic choice for asthma control, which is a heterogeneous airway inflammatory disease. Because of variable findings, we intend to evaluate the therapeutic effect and safety of azithromycin in asthma. Databases, including PubMed, EMBASE, Cochrane, and CNKI until 31 December 2017, were searched to identify available randomised controlled trials regarding azithromycin treatment for asthma. We identified seven studies involving 1520 cases that met our criteria. The mean difference for lung function (FEV1 , FVC, PEF), symptom assessment (ACQ, AQLQ), airway inflammation, and risk ratios for adverse events were extracted. Chi-square and I2 tests were applied to evaluate the heterogeneity among the studies towards each index with a random effect model or a fixed effect model. Pooled analysis shows that azithromycin administration results in no significant improvement in FEV1 (MD: 0.09, 95% CI -0.10 to 0.29, P = 0.36), PEF (MD: 11.76; 95% CI, -2.86 to 26.38, P = 0.11), total airway inflammatory cells (MD: -0.29; 95% CI, -1.38 to 0.80, P =  0.60), ACQ (MD: 0.05; 95% CI, -0.08 to 0.19, P = 0.44), and AQLQ (MD: 0.12; 95% CI, -0.02 to 0.26, P =  0.10). Moreover, no significant difference was detected in adverse events (Risk ratio 0.99; 95% CI, 0.82-1.19, P = 0.90). These findings demonstrate no beneficial clinical outcome of azithromycin in asthma control, and we propose that further prospective cohorts are warranted.

Correction to: Efficacy of intravenous plus intrathecal/intracerebral ventricle injection of polymyxin B for post-neurosurgical intracranial infections due to MDR/XDR Acinectobacter baumannii: a retrospective cohort study.

[This corrects the article DOI: 10.1186/s13756-018-0305-5.].

Efficacy of intravenous plus intrathecal/intracerebral ventricle injection of polymyxin B for post-neurosurgical intracranial infections due to MDR/XDR Acinectobacter baumannii: a retrospective cohort study.

Background: Post-neurosurgical intracranial infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii are difficult to treat and associated with high mortality. In this study, we analyzed the therapeutic efficacy of intravenous combined with intrathecal/intracerebral ventricle injection of polymyxin B for this type of intracranial infection. Methods: This retrospective study was conducted from January 2013 to September 2017 at the Second Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou,China) and included 61 cases for which cerebrospinal fluid (CSF) cultures were positive for multidrug-resistant or extensively drug-resistant A. baumannii after a neurosurgical operation. Patients treated with intravenous and intrathecal/intracerebral ventricle injection of polymyxin B were assigned to the intrathecal/intracerebral group, and patients treated with other antibiotics without intrathecal/intracerebral injection were assigned to the intravenous group. Data for general information, treatment history, and the results of routine tests and biochemistry indicators in CSF, clinical efficiency, microbiological clearance rate, and the 28-day mortality were collected and analyzed. Results: The rate of multidrug-resistant or extensively drug-resistant A. baumannii infection among patients who experienced an intracranial infection after a neurosurgical operation was 33.64% in our hospital. The isolated A. baumannii were resistant to various antibiotics, and most seriously to carbapenems (100.00% resistance rate to imipenem and meropenem), cephalosporins (resistance rates of 98.38% to cefazolin, 100.00% to ceftazidime, 100.00% to cefatriaxone, and 98.39% to cefepime). However, the isolated A. baumannii were completely sensitive to polymyxin B (sensitivity rate of 100.00%), followed by tigecycline (60.66%) and amikacin (49.18%). No significant differences in basic clinical data were observed between the two groups. Compared with the intravenous group, the intrathecal/intracerebral group had a significantly lower 28-day mortality (55.26% vs. 8.70%, P = 0.01) and higher rates of clinical efficacy and microbiological clearance (95.65% vs. 23.68%, P < 0.001; 91.30% vs. 18.42%, P < 0.001, respectively). Conclusions: Intravenous plus intrathecal/intracerebral ventricle injection of polymyxin B is an effective regimen for treating intracranial infections caused by multidrug-resistant or extensively drug-resistant A. baumannii.

Melatonin Attenuates Pain Hypersensitivity and Decreases Astrocyte-Mediated Spinal Neuroinflammation in a Rat Model of Oxaliplatin-Induced Pain.

Neuroinflammatory response in spinal dorsal horn has been demonstrated to be a critical factor in oxaliplatin-induced pain. Melatonin has been shown to have anti-inflammatory and anti-allodynia effects in both preclinical and clinical studies. In the present study, we investigated the role of systemic administration of melatonin on oxaliplatin-induced pain. Intraperitoneal (i.p.) injection with oxaliplatin induced significantly mechanical allodynia and thermal hyperalgesia. Melatonin (i.p.) significantly alleviated mechanical allodynia and thermal hyperalgesia in the oxaliplatin but not sham-treated rats. The attenuation of nociceptive response persisted at least to 3 days after melatonin injection, throughout the entire observing window. Immunohistochemistry showed that oxaliplatin induced a significant increase of glial fibrillary acidic protein (GFAP) immunodensities, which could be suppressed by melatonin. Western blotting showed that GFAP protein levels were significantly elevated in the oxaliplatin-vehicle group. Melatonin significantly decreased oxaliplatin-induced upregulation of GFAP expressions. Oxaliplatin injection also enhanced the messenger RNA (mRNA) expressions of cytokines including interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) and chemokines including monocyte chemoattractant protein-1 (MCP-1) and monocyte inflammatory protein-1 (MIP-1α) in the spinal dorsal horn, which could be significantly repressed by melatonin. In vitro study showed that mRNA levels of TNF-α, IL-1ß, MCP-1, and MIP-1α in primarily astrocytes were significantly increased after lipopolysaccharide (LPS, 1 µg/ml) stimulation. Melatonin (10 and 100 µM) greatly inhibited synthesis of these inflammatory mediators, in a dose-related manner. Conclusively, our data provide a novel implication of anti-nociceptive mechanism of melatonin in chemotherapy-related pain.

H2S inhibits angiotensin II-induced atrial Kv1.5 upregulation by attenuating Nox4-mediated ROS generation during atrial fibrillation.

Our previous study demonstrated that angiotensin II (Ang II) upregulates the expression of Kv1.5, a promising target for atrial fibrillation (AF) therapy, by activating ROS-dependent P-Smad2/3 and P-ERK 1/2. A recent study showed that hydrogen sulfide (H2S) may modulate the effects of angiotensin II (Ang II) by inhibiting the NADPH oxidase 4 (Nox4)-ROS signaling in the heart. The present study aimed to determine whether H2S is involved in the regulation of atrial Kv1.5 via ROS-related mechanisms in AF. Cultured neonatal rat atrial myocytes and a beagle model of AF were used for this study. In the neonatal rat atrial myocytes, quantitative PCR and enzyme immunoassays revealed that the mRNA expression levels of angiotensinogen, angiotensin-converting enzyme, and Ang II type I receptor (AT1R) and the Ang II supernatant concentration were significantly increased by hydrogen peroxide (H2O2) incubation, and these H2O2-induced alterations were reversed by diphenyleneiodonium, apocynin and H2S supplementation. Flow cytometry and Western blotting revealed that blockade of H2S biosynthesis using dl-propargylglycine increased ROS production and the expression of Ang II and Kv1.5. Sodium hydrosulfide (an exogenous H2S donor) and Nox4 siRNA inhibited Ang II-induced ROS production and Ang II-induced expression of Kv1.5, P-Smad2/3, P-ERK 1/2. Sodium hydrosulfide suppressed the Ang II-induced upregulation of Nox4. In our beagle AF model, 24 h of rapid atrial pacing (RAP) increased the atrial Ang II concentration, ROS production and the protein expression of Nox4, Kv1.5, P-Smad2/3 and P-ERK 1/2. These RAP-induced changes were inhibited by H2S supplementation and losartan (an AT1R blocker) pretreatment. In conclusion, our study indicates that H2S downregulates Ang II-induced atrial Kv1.5 expression by attenuating Nox4-related ROS-triggered P-Smad2/3 and P-ERK 1/2 activation during AF. H2S supplementation would be beneficial for AF treatment via the suppression of atrial Kv1.5 expression.

Downregulation of VEGF and upregulation of TL1A expression induce HUVEC apoptosis in response to high glucose stimuli.

High glucose­induced endothelial cell apoptosis is considered to be the initiator of diabetes­associated vascular complications. Experiments in vivo and in vitro have demonstrated that high glucose levels contribute to the apoptosis of endothelial cells by mediating cellular dysfunction and metabolic disorder via the production of various cytokines. As the most important endogenous vascular regulators, the balance between pro­proliferative effector vascular endothelial growth factor (VEGF) and anti­proliferative effector tumor necrosis factor­like cytokine 1A (TL1A) is important in the modulation of endothelial cell survival and proliferation, and neovascularization. The present study aimed to explore whether the imbalance between VEGF and TL1A affected the apoptosis of human umbilical vein endothelial cells (HUVECs) exposed to high glucose conditions and then further investigated the potential mechanism. The results showed that the downregulation of VEGF in combination with the upregulation of TL1A in response to high glucose levels led to enhanced HUVEC apoptosis. Further experiments revealed that silencing high glucose­induced TL1A expression using TL1A small interfering (si)RNA or the overexpression of VEGF by transfection with VEGF DNA resulted in a reduced HUVEC apoptosis rate compared with the controls. The effects occurred by attenuating and activating the phosphoinositide 3­kinase/Akt/endothelial nitric oxide synthase pathway, respectively. In addition, VEGF and TL1A inhibited each other in hyperglycemia. In conclusion, these findings provide theoretical support for the further investigation of novel therapeutic strategies designed to maintain the balance between VEGF and TL1A and, thus, to prevent the onset and progression of endothelial cell apoptosis in response to high glucose stimuli.

Tanshinone IIA Attenuates Chronic Pancreatitis-Induced Pain in Rats via Downregulation of HMGB1 and TRL4 Expression in the Spinal Cord.

BACKGROUND: Chronic pancreatitis (CP) is a long-standing inflammation of the exocrine pancreas, which typically results in severe and constant abdominal pain. Previous studies on the mechanisms underlying CP-induced pain have primarily focused on the peripheral nociceptive system. A role for a central mechanism in the mediation or modulation of abdominal pain is largely unknown. Tanshinone IIA (TSN IIA), an active component of the traditional Chinese medicine Danshen, exhibits anti-inflammatory properties via downregulation of the expression of high-mobility group protein B1 (HMGB1), a late proinflammatory cytokine. HMGB1 binds and activates toll-like receptor 4 (TLR4) to induce spinal astrocyte activation and proinflammatory cytokine release in neuropathic pain. OBJECTIVE: In this study, we investigated the effect of TSN IIA on pain responses in rats with trinitrobenzene sulfonic acid (TNBS)-induced CP. The roles of central mechanisms in the mediation or modulation of CP were also investigated. STUDY DESIGN: A randomized, double-blind, placebo-controlled animal trial. METHODS: CP was induced in rats by intrapancreatic infusion of trinitrobenzene sulfonic acid (TNBS). Pancreatic histopathological changes were characterized with semi-quantitative scores. The abdomen nociceptive behaviors were assessed with von Frey filaments. The effects of intraperitoneally administered TSN IIA on CP-induced mechanical allodynia were tested. The spinal protein expression of HMGB1 was determined by western blot. The spinal mRNA and protein expression of proinflammatory cytokines IL-1ß, TNF-α, and IL-6 were determined by RT-PCR and western blot, respectively. The spinal expression of the HMGB1 receptor TRL4 and the astrocyte activation marker glial fibrillary acidic protein (GFAP) were determined by western blot or immunohistological staining after intraperitoneal injection of TSN IIA or intrathecal administration of a neutralizing anti-HMGB1 antibody. RESULTS: TNBS infusion resulted in pancreatic histopathological changes of chronic pancreatitis and mechanical allodynia in rats. TSN IIA significantly attenuated TNBS-induced mechanical allodynia in a dose-dependent manner. TNBS significantly increased the spinal expression of HMGB1 and proinflammatory cytokines IL-1ß, TNF-α, and IL-6. These TNBS-induced changes were significantly inhibited by TSN IIA in a dose-dependent manner. Furthermore, TSN IIA, but not the neutralizing anti-HMGB1 antibody, significantly inhibited TNBS-induced spinal TLR4 and GFAP expression. LIMITATIONS: In addition to TLR4, HMGB1 can also bind to toll-like receptor-2 (TLR2) and the receptor for advanced glycation end products (RAGE). Additional studies are warranted to ascertain whether HMGB1 contributes to CP-induced pain through activation of these receptors. CONCLUSIONS: Our results suggest that spinal HMGB1 contributes to the development of CP-induced pain and can potentially be a therapeutic target. TSN IIA attenuates CP-induced pain via downregulation of spinal HMGB1 and TRL4 expression. Therefore, TSN IIA may be a potential anti-nociceptive drug for the treatment of CP-induced pain.

High fever and multi-nodular lung consolidations after whole lung lavage in a patient with pulmonary alveolar proteinosis.

INTRODUCTION: Whole lung lavage is the most effective method to treat pulmonary alveolar proteinosis (PAP), and most potential complications occur often during the lavage process, but few happen after lavage. Theoretically, pulmonary edema would be more common after whole lung lavage. However, no such case was reported in the literature. CASE DESCRIPTION: A 47-year-old Chinese male patient with PAP was referred to our hospital for whole lung lavage treatment. Although the clinical manifestations of PAP were improved, high fever was happened and multi-nodular consolidations in chest CT scan were occurred after whole lung lavage. Secondary lung infection was suspected, but the patient was not treated with antibiotics immediately. After therapies like liquid limitation, glucocorticoid administration and diuretic treatment, the patient was improved gradually. Namely, newly nodular consolidations were almost completely absorbed in three days, along with the complete recovery of body temperature and associated inflammatory biomarkers. The diagnosis of secondary infection was excluded, and the final diagnosis of lavage fluid-induced pulmonary edema was confirmed. DISCUSSION AND EVALUATION: No such case has been reported that lavage fluid-induced pulmonary edema is manifested by high fever and multi-consolidations in chest CT scan, which is similar to the secondary infection. CONCLUSIONS: For the first time, we described a rare complication of lavage fluid-induced pulmonary edema after whole lung lavage. As the obvious differences in treatments, it is very important for physicians to differentiate it from secondary infection.

Angiotensin II upregulates Kv1.5 expression through ROS-dependent transforming growth factor-beta1 and extracellular signal-regulated kinase 1/2 signalings in neonatal rat atrial myocytes.

Kv1.5 potassium channel represents a promising target for atrial fibrillation (AF) therapy. During AF, the renin-angiotensin system is markedly activated. Recent evidence indicates that angiotensin II (Ang II) can upregulate Kv1.5 channel, but the mechanism remains unknown. In this study, we report that Ang II-mediated transforming growth factor-beta1 (TGF-ß1)/Smad2/3 and extracellular signal-regulated kinase (ERK) 1/2 signalings are involved in atrial Kv1.5 expression. In neonatal rat atrial myocytes, quantitative PCR and Western blotting revealed that Ang II upregulated TGF-ß1, synapse-associated protein 97 (SAP97) and Kv1.5 expression in a time- and concentration-dependent manner. The Ang II-induced upregulation of Kv1.5, SAP97 and phosphorylated Smad2/3 (P-Smad2/3) were reversed by the Ang II type 1 (AT1) receptor antagonist losartan, an anti-TGF-ß1 antibody and the ERK 1/2 inhibitor PD98059 but not by the AT2 receptor antagonist PD123319. mRNA knockdown of either Smad2 or Smad3 blocked Ang II-induced expression of Kv1.5 and SAP97. These data suggest that AT1 receptor/TGF-ß1/P-Smad2/3 and ERK 1/2 signalings are involved in Ang II-induced Kv1.5 and SAP97 expression. Flow cytometry and Western blotting revealed that losartan and the anti-TGF-ß1 antibody diminished Ang II-induced reactive oxygen species (ROS) generation and that the antioxidants diphenyleneiodonium and N-acetyl cysteine inhibited Ang II-induced expression of P-Smad2/3, phosphorylated ERK (P-ERK) 1/2, Kv1.5, SAP97, suggesting that ROS participate in Kv1.5 and SAP97 regulation by modulating Ang II-induced P-Smad2/3 and P-ERK 1/2 expression. In conclusion, we demonstrate that ROS-dependent Ang II/AT1 receptor/TGF-ß1/P-Smad2/3 and Ang II/ERK 1/2 signalings are involved in atrial Kv1.5 and SAP97 expression. Antioxidants would be beneficial for AF treatment through inhibiting atrial Kv1.5 expression.

Regulation of recombinant Trichinella spiralis 53-kDa protein (rTsP53) on alternatively activated macrophages via STAT6 but not IL-4Rα in vitro.

Classically activated macrophages (M1) or alternatively activated macrophages (M2) have different functions during helminth infections including Trichinella spiralis (T. spiralis). The excretory/secretory antigens (ESA) of T. spiralis can inhibit macrophage pro-inflammatory cytokines production. However, the specific molecules of ESA that regulate macrophages have not been identified. We previously reported that recombinant T. spiralis derived molecule 53-kDa protein (rTsP53) had protected mice from colitis. Furthermore, in the present study in vitro, we investigated rTsP53 showed anti-inflammatory function by inducing peritoneal macrophages to M2 with expressing M2 molecules of mannose receptor (MR), a novel mammalian lectin (Ym1), arginase-1 (Arg1), and interleukin (IL)-10. Next, we found the effect of rTsP53 on M2 independently of IL-4Rα. But rTsP53 can act dependently on signal transducers and activators of transcription 6 (STAT6). These results further imply that rTsP53 has potential as prospective immuno-therapeutics for inflammatory disorders.