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BACKGROUND: This article reports a chemical burn incident that occurred on August 7th, 2005, when a Matsa typhoon hit Shanghai, China. This is the largest chemical burn incident reported in the literature for 20 years in China, involving 118 alkali burn patients who were rescued by the Burn Department of Shanghai Changhai Hospital independently. METHODS: The scene of the incident was investigated, and the clinical, emergency and hospitalized data of the patients were summarized. RESULTS: The main injurious chemical was a water solution of sodium hydroxide and ammonium chloride. The 118 victims were mostly young men with 5%TBSA deep thickness burn of both lower extremities, including 31 patients who had additional light coughing. Of 58 patients who were finally hospitalized, 42 patients received surgical treatment. Most of these patients recovered within 1 month. There were no deaths. DISCUSSION: Retrospective analysis of the therapeutic data of the incident demonstrates that pre-designed disaster planning for emergency management of mass burn patients, an effective command group, accurate assessment of pathological conditions, and correct allocation of different casualties are key elements in successful management in a mass casualty even involving burn patients. In addition, it is essential for specialized personnel to take part in emergency treatment of chemical burns. [ABSTRACT FROM AUTHOR]

Background Context: The North American Spine Society's (NASS) Evidence-Based Clinical Guideline for the Diagnosis and Treatment of Adults with Osteoporotic Vertebral Compression Fractures features evidence-based recommendations for diagnosing and treating adult patients with osteoporotic vertebral compression fractures. The guideline is intended to reflect contemporary treatment concepts for osteoporotic vertebral compression fractures as reflected in the highest quality clinical literature available on this subject as of September 2020., Purpose: The purpose of the guideline is to provide an evidence-based educational tool to assist spine specialists when making clinical decisions for adult patients with osteoporotic vertebral compression fractures. This article provides a brief summary of the evidence-based guideline recommendations for diagnosing and treating patients with this condition., Study Design: This is a guideline summary review., Methods: This guideline is the product of NASS' Clinical Practice Guidelines Committee. The methods used to develop this guideline are detailed in the complete guideline and technical report available on the NASS website. In brief, a multidisciplinary work group of spine care specialists convened to identify clinical questions to address in the guideline. The literature search strategy was developed in consultation with a medical librarian. Upon completion of the systematic literature search, evidence relevant to the clinical questions posed in the guideline was reviewed. Work group members utilized NASS evidentiary table templates to summarize study conclusions, identify study strengths and weaknesses, and assign levels of evidence. Work group members participated in recommendation meetings to update and formulate evidence-based recommendations and incorporate expert opinion when necessary. The draft guideline was submitted to an internal and external peer review process and ultimately approved by the NASS Board of Directors., Results: Twenty-nine clinical questions were addressed, and the answers are summarized in this article. The respective recommendations were graded according to the levels of evidence of the supporting literature., Conclusions: The evidence-based clinical guideline has been created using techniques of evidence-based medicine and best available evidence to aid practitioners in the diagnosis and treatment of adult patients with osteoporotic vertebral compression fractures. The entire guideline document, including the evidentiary tables, literature search parameters, literature attrition flowchart, suggestions for future research, and all of the references, is available electronically on the NASS website at http://www.spine.org/guidelines., (Copyright © 2025. Published by Elsevier Inc.)

Objective: To investigate the effect of information management of intravenous drugs on anemia in maintenance hemodialysis patients. Methods: The information management of intravenous drugs was a management system developed by the Hemodialysis Center of Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital in April 2020. The parameters six months before and after the use of the information management system were retrospectively collected and compared, including the rate of reaching the standard of hemoglobin, ferritin, transferrin saturation rate and the incidence of cardiovascular events. Specifically, the control stage was from October 2019 to March 2020, which was before the use of information management, and the study stage was from April to September 2020, which was after the use of information management. Results: There were 285 patients (190 males and 95 females) included in the control stage, with an average age of (62.4±13.2) years, while 278 patients (193 males and 85 females) were included in the study stage, with an average age of (62.8±13.2) years. Compared with the control stage, the rate of reaching the standard of hemoglobin [47.8% (797/1 668) vs 40.2% (687/1 710), P <0.001], ferritin [39.0% (217/556) vs 31.2% (178/570), P =0.006], and transferrin saturation [64.7% (360/556) vs 58.6% (334/570), P =0.034] increased in the study stage. The incidence of cardiovascular events in the study stage was 11.2% (31/278), which was significantly lower than that in the control stage [16.5% (47/285)] ( P =0.043). Conclusion: The information management of intravenous drugs in the hemodialysis center may help improve the anemia status in maintenance hemodialysis patients.

Background: The most common presentation of cluneal neuropathy is ipsilateral low back and gluteal pain. Cluneal neuralgia has been described historically in surgical contexts, with much of the description and treatment related to entrapment and decompression, respectively. Treatment options for addressing axial low back pain have evolved with advancements in the field of interventional pain medicine, though clinical results remain inconsistent. Recent attention has turned toward peripheral nerve stimulation. Nonsurgical interventions targeting the superior and medial cluneal nerve branches have been performed in cases of low back and buttock pain, but there is no known review of the resulting evidence to support these practices., Objectives: In this manuscript we provide a robust exploration and analysis of the available literature regarding treatment options for cluneal neuropathy. We provide clinical manifestations and recommendations for future study direction., Study Design: Narrative review., Methods: This was a systematic, evidence-based narrative, performed after extensive review of the literature to identify all manuscripts associated with interventional treatment of the superior and medial cluneal nerves., Results: Eleven manuscripts fulfilled inclusion criteria. Interventional treatment of the superior and middle cluneal nerves includes blockade with corticosteroid, alcohol neurolysis, peripheral nerve stimulation, radiofrequency neurotomy, and surgical decompression., Limitations: The supportive evidence for interventions in cluneal neuropathy is largely lacking due to small, uncontrolled, observational studies with multiple confounding factors. There is no standardized definition of cluneal neuropathy., Conclusion: Limited studies promote beneficial effects from interventions intended to target cluneal neuropathy. Despite increased emphasis and treatment options for this condition, there is little consensus on the diagnostic criteria, endpoints, and measures of therapeutics, or procedural techniques for blocks, radiofrequency, and neuromodulation. It is imperative to delineate pathology associated with the cluneal nerves and perform rigorous analysis of associated treatment options.

Leukoaraiosis (LA) is commonly found in aging healthy people but its pathophysiological mechanism is not entirely known. Furthermore, there is still a lack of effective pathological biomarkers that can be used to identify the early stage of LA. Our aim was to investigate the white matter structural network in asymptomatic patients with the early stage of LA. Tractography data of 35 asymptomatic patients and 20 matched healthy controls (HCs) based on diffusion kurtosis imaging (DKI) were analysed by using graph theory approaches and tract-based spatial statistics (TBSS). Diffusion parameters measured within the ALAs and HCs were compared. Decreased clustering coefficient and local efficiency values of the overall topological white matter network were observed in the ALAs compared with those of the HCs. Participants in the asymptomatic group also had lower nodal efficiency in the left triangular part of the inferior frontal gyrus, left parahippocampal gyrus, right calcarine fissure and surrounding cortex, right temporal pole of the superior temporal gyrus and left middle temporal gyrus compared to the ALAs. Moreover, similar hub distributions were found within participants in the two groups. In this study, our data demonstrated a topologic efficiency abnormalities of the structural network in asymptomatic patients with leukoaraiosis. The structural connectome provides potential connectome-based measures that may be helpful for detecting leukoaraiosis before clinical symptoms evolve.

This article analyzed the medical records of two patients with Vibrio vulnificus primary sepsis who were admitted to the First Affiliated Hospital of Naval Medical University and reviewed the latest literature. On November 6, 2019, a 54-year-old male patient was admitted to the hospital. The patient's lower limbs were red, swollen, and painful with ecchymosis and hemorrhagic bullae after he ate freshwater products. The emergency fasciotomy was performed 3 h after admission, and the multiple organ failure occurred after operation. The patient was given up treatment 24 h after admission. On August 12, 2020, a 73-year-old male patient was admitted to the hospital. He was in shock state on admission and had hemorrhagic bullae on his right lower limb after he ate seafood. At 3 h post admission, he underwent emergency surgical exploration and amputation of right thigh. Six days later, he received negative pressure wound treatment on the stump. On the 13 th day post admission, his families forgo the active treatment and he died 15 d after admission. The two cases were both failed to be diagnosed at the first time, and the disease progressed rapidly. Necrotizing fasciitis and multiple organ failure occurred. After the diagnosis was confirmed, timely fasciotomy and high amputation were performed respectively. The microbiological examinations both reported Vibrio vulnificus . Although the 2 cases were not cured successfully, the course of disease and some indexes of patient with early amputation were better than those of patients with fasciotomy. Vibrio vulnificus is widely distributed and frequently detected in fresh water products. The pathogenic pathway is fuzzy and complex, and it is easy to be misdiagnosed. It is necessary to establish the treatment process of Vibrio vulnificus sepsis. Early and aggressive surgical intervention should be carried out as soon as possible, fasciotomy and debridement should be thorough, and the patients with hemorrhagic bullae should be amputated early. Postoperative comprehensive measures are also important for improving the survival rate of patients.

Objective: Determine the effectiveness of intraosseous basivertebral nerve radiofrequency neurotomy for the treatment of chronic low back pain with type 1 or 2 Modic changes., Design: Systematic review., Population: Persons aged ≥18 years with chronic low back pain with type 1 or 2 Modic changes., Intervention: Intraosseous basivertebral nerve radiofrequency neurotomy., Comparison: Sham, placebo procedure, active standard care treatment, or none., Outcomes: The primary outcome of interest was the proportion of individuals with ≥50% pain reduction. Secondary outcomes included ≥10-point improvement in function as measured by Oswestry Disability Index as well as ≥2-point reduction in pain score on the Visual Analog Scale or Numeric Rating Scale, and decreased use of pain medication., Methods: Three reviewers independently assessed publications before May 15, 2020, in MEDLINE and Embase and the quality of evidence was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation framework., Results: Of the 725 publications screened, seven publications with 321 participants were ultimately included. The reported 3-month success rate for ≥50% pain reduction ranged from 45% to 63%. Rates of functional improvement (≥10-point Oswestry Disability Index improvement threshold) ranged from 75% to 93%. For comparison to sham treatment, the relative risk of treatment success defined by ≥50% pain reduction and ≥10-point Oswestry Disability Index improvement was 1.25 (95% confidence interval [CI]: .88-1.77) and 1.38 (95% CI: 1.10-1.73), respectively. For comparison to continued standard care treatment the relative risk of treatment success defined by ≥50% pain reduction and ≥10-point Oswestry Disability Index improvement was 4.16 (95% CI: 2.12-8.14) and 2.32 (95% CI: 1.52-3.55), respectively., Conclusions: There is moderate-quality evidence that suggests this procedure is effective in reducing pain and disability in patients with chronic low back pain who are selected based on type 1 or 2 Modic changes, among other inclusion and exclusion criteria used in the published literature to date. Success of the procedure appears to be dependent on effective targeting of the BVN. Non-industry funded high-quality, large prospective studies are needed to confirm these findings., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A 25-year-old man with extensive burn due to industrial dust explosion was admitted to the First Affiliated Hospital of Naval Medical University on 16th October, 2018. Four days after the first skin grafting and vacuum sealing drainage surgery, the patient developed signs of uncontrolled severe inflammation and shock. However, several atypical manifestations interfered the diagnosis of septic shock. After giving emergency treatment including fluid resuscitation, broad-spectrum antibiotics, and administration of vasopressor agents, the patient's condition was alleviated, but quickly relapsed and deteriorated, with acute pulmonary edema appeared in the evening of the same day. Finally, the condition was reversed by completely removing the negative pressure devices on upper limbs and thorough dressing change. This case suggests that the diagnosis and treatment of infection in patients with extensive burn need comprehensive analysis. Timely intervention of the wound is the key to control the exacerbation of sepsis. In addition, the possibility of pulmonary edema in patients with sepsis should be on high alert.

Background Context: The North American Spine Society's (NASS) Evidence Based Clinical Guideline for the Diagnosis and Treatment of Low Back Pain features evidence-based recommendations for diagnosing and treating adult patients with nonspecific low back pain. The guideline is intended to reflect contemporary treatment concepts for nonspecific low back pain as reflected in the highest quality clinical literature available on this subject as of February 2016., Purpose: The purpose of the guideline is to provide an evidence-based educational tool to assist spine specialists when making clinical decisions for adult patients with nonspecific low back pain. This article provides a brief summary of the evidence-based guideline recommendations for diagnosing and treating patients with this condition., Study Design: This is a guideline summary review., Methods: This guideline is the product of the Low Back Pain Work Group of NASS' Evidence-Based Clinical Guideline Development Committee. The methods used to develop this guideline are detailed in the complete guideline and technical report available on the NASS website. In brief, a multidisciplinary work group of spine care specialists convened to identify clinical questions to address in the guideline. The literature search strategy was developed in consultation with medical librarians. Upon completion of the systematic literature search, evidence relevant to the clinical questions posed in the guideline was reviewed. Work group members utilized NASS evidentiary table templates to summarize study conclusions, identify study strengths and weaknesses, and assign levels of evidence. Work group members participated in webcasts and in-person recommendation meetings to update and formulate evidence-based recommendations and incorporate expert opinion when necessary. The draft guideline was submitted to an internal and external peer review process and ultimately approved by the NASS Board of Directors., Results: Eighty-two clinical questions were addressed, and the answers are summarized in this article. The respective recommendations were graded according to the levels of evidence of the supporting literature., Conclusions: The evidence-based clinical guideline has been created using techniques of evidence-based medicine and best available evidence to aid practitioners in the diagnosis and treatment of adult patients with nonspecific low back pain. The entire guideline document, including the evidentiary tables, literature search parameters, literature attrition flowchart, suggestions for future research, and all of the references, is available electronically on the NASS website at https://www.spine.org/ResearchClinicalCare/QualityImprovement/ClinicalGuidelines.aspx., (Copyright © 2020. Published by Elsevier Inc.)

The early accurate diagnosis of burn depth is of great significance in determining the corresponding clinical intervention methods and judging the prognosis quality of burn patients. However, the current diagnostic method of burn depth still relies mainly on the empirical subjective judgment of clinicians, with low diagnostic accuracy. Especially for deep partial-thickness burn wounds, the error of early diagnosis is pretty big. In recent years, with the rapid development of artificial intelligence technology, deep learning algorithm combined with image analysis technology can better identify and analyze the information of medical images. This article reviews the research progress of artificial intelligence technology in the diagnosis of burn depth.

Background: Cost report cards have demonstrated variation in intraoperative supply costs and may allow comparisons between surgeons. However, cost data are complex and, if not properly vetted, may be inaccurate., Methods: A retrospective assessment of intraoperative supply costs for consecutive laparoscopic cholecystectomies (2013-2017) at a 4-facility academic center was performed. Using unadjusted data (akin to an auto-generated report card), surgeons were ranked and highest to lowest-cost ratios were calculated. Then, four stepwise adjustments were performed: (1) excluded non-comparable operations and low volume (< 10 cases) surgeons, (2) eliminated outlier cases based on instrument profiles, (3) stratified by facility, and (4) adjusted prices (assigned one price; corrected aberrant/missing prices). Surgeon rank and highest to lowest-cost ratios were then re-calculated., Results: The unadjusted data identified 1392 cases for 33 surgeons (range, 1-317 cases). The ratio between the highest cost and lowest cost surgeon was 4.13. Steps 1 and 2 excluded 272 cases and 15 surgeons. Facility sample sizes ranged from 144 to 621 (step 3). Adjusting prices (step 4) required manual review of 472 unique items: 45% had > 1 price and 16 had missing prices. After all adjustments, surgeons had different rankings and highest to lowest-cost ratios within sites were smaller (ratio range, 1.17-2.10)., Conclusions: Evaluating surgeons based on intraoperative supply costs is sensitive to analytic methods. Surgeons who were initially considered cost outliers became the least expensive within a given site. Auto-generated cost report cards may require additional analyses to produce accurate comparative assessments.

Loss of secretory IgA is common in the small airways of patients with chronic obstructive pulmonary disease and may contribute to disease pathogenesis. Using mice that lack secretory IgA in the airways due to genetic deficiency of polymeric Ig receptor (pIgR -/- mice), we investigated the role of neutrophils in driving the fibrotic small airway wall remodeling and emphysema that develops spontaneously in these mice. By flow cytometry, we found an increase in the percentage of neutrophils among CD45 + cells in the lungs, as well as an increase in total neutrophils, in pIgR -/- mice compared with wild-type controls. This increase in neutrophils in pIgR -/- mice was associated with elastin degradation in the alveolar compartment and around small airways, along with increased collagen deposition in small airway walls. Neutrophil depletion using anti-Ly6G antibodies or treatment with broad-spectrum antibiotics inhibited development of both emphysema and small airway remodeling, suggesting that airway bacteria provide the stimulus for deleterious neutrophilic inflammation in this model. Exogenous bacterial challenge using lysates prepared from pathogenic and nonpathogenic bacteria worsened neutrophilic inflammation and lung remodeling in pIgR -/- mice. This phenotype was abrogated by antiinflammatory therapy with roflumilast. Together, these studies support the concept that disruption of the mucosal immune barrier in small airways contributes to chronic obstructive pulmonary disease progression by allowing bacteria to stimulate chronic neutrophilic inflammation, which, in turn, drives progressive airway wall fibrosis and emphysematous changes in the lung parenchyma.

Objective: To observe the clinical efficacy and safety of Shuanghu Qinggan Granule ( , SQG) plus Yigan Yiqi Jieyu Granule (, YYJG) combined with lamivudine (LAM) on chronic hepatitis B (CHB) patients., Methods: The study was a multicenter, randomized, double-blinded and parallel controlled trial. A total of 320 patients were randomly allocated into 2 groups equally: 160 patients (treatment group) were given SQG and YYJG combined with LAM; and 160 patients (control group) were given LAM plus Chinese herb placebo, respectively. Liver functions, hepatitis B envelop antigen (HBeAg) titer levels, and hepatitis B virus DNA (HBV-DNA) load were monitored., Results: (1) In the 48th week, the treatment group showed superior HBeAg seroconversion rate than that in the control group (38.0% vs. 24.0%, P<0.05). (2) In the 48th week, the treatment group demonstrated lower HBeAg titer than that in the control group (P<0.05). (3) In the 12th, 24th, 48th week, there was no statistical significance in HBV-DNA response rate between the two groups. (4) In the 12th week, the level of glutamyl transpeptidase (GGT) was significantly decreased in the treatment group compared with the control group (P<0.05); in the 36th week, the levels of alanine aminotransferase and aspartate transaminase were significantly lower in the treatment group than those in the control group (P<0.05)., Conclusion: The protocol of SQG and YYJG combined with LAM to treat CHB showed superior efficacy than LAM monotherapy.

Although epithelial NF-κB signaling is important for lung carcinogenesis, NF-κB inhibitors are ineffective for cancer treatment. To explain this paradox, we studied mice with genetic deletion of IKKβ in myeloid cells and found enhanced tumorigenesis in Kras(G12D) and urethane models of lung cancer. Myeloid-specific inhibition of NF-κB augmented pro-IL-1β processing by cathepsin G in neutrophils, leading to increased IL-1β and enhanced epithelial cell proliferation. Combined treatment with bortezomib, a proteasome inhibitor that blocks NF-κB activation, and IL-1 receptor antagonist reduced tumor formation and growth in vivo. In lung cancer patients, plasma IL-1β levels correlated with poor prognosis, and IL-1β increased following bortezomib treatment. Together, our studies elucidate an important role for neutrophils and IL-1β in lung carcinogenesis and resistance to NF-κB inhibitors., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mechanisms driving persistent airway inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood. As secretory immunoglobulin A (SIgA) deficiency in small airways has been reported in COPD patients, we hypothesized that immunobarrier dysfunction resulting from reduced SIgA contributes to chronic airway inflammation and disease progression. Here we show that polymeric immunoglobulin receptor-deficient (pIgR(-/-)) mice, which lack SIgA, spontaneously develop COPD-like pathology as they age. Progressive airway wall remodelling and emphysema in pIgR(-/-) mice are associated with an altered lung microbiome, bacterial invasion of the airway epithelium, NF-κB activation, leukocyte infiltration and increased expression of matrix metalloproteinase-12 and neutrophil elastase. Re-derivation of pIgR(-/-) mice in germ-free conditions or treatment with the anti-inflammatory phosphodiesterase-4 inhibitor roflumilast prevents COPD-like lung inflammation and remodelling. These findings show that pIgR/SIgA deficiency in the airways leads to persistent activation of innate immune responses to resident lung microbiota, driving progressive small airway remodelling and emphysema.

Several studies have demonstrated that NF-κB activation is common in lung cancer; however, the mechanistic links between NF-κB signaling and tumorigenesis remain to be fully elucidated. We investigated the function of NF-κB signaling in epidermal growth factor receptor (EGFR)-mutant lung tumors using a transgenic mouse model with doxycycline (dox)-inducible expression of oncogenic EGFR in the lung epithelium with or without a dominant inhibitor of NF-κB signaling. NF-κB inhibition resulted in a significant reduction in tumor burden in both EGFR tyrosine kinase inhibitor (TKI)-sensitive and resistant tumors. However, NF-κB inhibition did not alter epithelial cell survival in vitro or in vivo, and no changes were detected in activation of EGFR downstream signaling pathways. Instead, we observed an influx of inflammatory cells (macrophages and neutrophils) in the lungs of mice with oncogenic EGFR expression that was blocked in the setting of NF-κB inhibition. To investigate whether inflammatory cells play a role in promoting EGFR-mutant lung tumors, we depleted macrophages and neutrophils during tumorigenesis and found that neutrophil depletion had no effect on tumor formation, but macrophage depletion caused a significant reduction in tumor burden. Together, these data suggest that epithelial NF-κB signaling supports carcinogenesis in a non-cell autonomous manner in EGFR-mutant tumors through recruitment of pro-tumorigenic macrophages.

Although numerous studies have demonstrated a critical role for canonical NF-κB signaling in inflammation and disease, the function of the noncanonical NF-κB pathway remains ill-defined. In lung tissue from patients with acute respiratory distress syndrome, we identified increased expression of the noncanonical pathway component p100/p52. To investigate the effects of p52 expression in vivo, we generated a novel transgenic mouse model with inducible expression of p52 in Clara cell secretory protein-expressing airway epithelial cells. Although p52 overexpression alone did not cause significant inflammation, p52 overexpression caused increased lung inflammation, injury, and mortality following intratracheal delivery of Escherichia coli LPS. No differences in cytokine/chemokine expression were measured between p52-overexpressing mice and controls, but increased apoptosis of Clara cell secretory protein-positive airway epithelial cells was observed in transgenic mice after LPS stimulation. In vitro studies in lung epithelial cells showed that p52 overexpression reduced cell survival and increased the expression of several proapoptotic genes during cellular stress. Collectively, these studies demonstrate a novel role for p52 in cell survival/apoptosis of airway epithelial cells and implicate noncanonical NF-κB signaling in the pathogenesis of acute respiratory distress syndrome., (Copyright © 2016 by The American Association of Immunologists, Inc.)

Rationale: Up to 20% of cases of idiopathic interstitial pneumonia cluster in families, comprising the syndrome of familial interstitial pneumonia (FIP); however, the genetic basis of FIP remains uncertain in most families., Objectives: To determine if new disease-causing rare genetic variants could be identified using whole-exome sequencing of affected members from FIP families, providing additional insights into disease pathogenesis., Methods: Affected subjects from 25 kindreds were selected from an ongoing FIP registry for whole-exome sequencing from genomic DNA. Candidate rare variants were confirmed by Sanger sequencing, and cosegregation analysis was performed in families, followed by additional sequencing of affected individuals from another 163 kindreds., Measurements and Main Results: We identified a potentially damaging rare variant in the gene encoding for regulator of telomere elongation helicase 1 (RTEL1) that segregated with disease and was associated with very short telomeres in peripheral blood mononuclear cells in 1 of 25 families in our original whole-exome sequencing cohort. Evaluation of affected individuals in 163 additional kindreds revealed another eight families (4.7%) with heterozygous rare variants in RTEL1 that segregated with clinical FIP. Probands and unaffected carriers of these rare variants had short telomeres (<10% for age) in peripheral blood mononuclear cells and increased T-circle formation, suggesting impaired RTEL1 function., Conclusions: Rare loss-of-function variants in RTEL1 represent a newly defined genetic predisposition for FIP, supporting the importance of telomere-related pathways in pulmonary fibrosis.

Rationale: Asymptomatic relatives of patients with familial interstitial pneumonia (FIP), the inherited form of idiopathic interstitial pneumonia, carry increased risk for developing interstitial lung disease., Objectives: Studying these at-risk individuals provides a unique opportunity to investigate early stages of FIP pathogenesis and develop predictive models of disease onset., Methods: Seventy-five asymptomatic first-degree relatives of FIP patients (mean age, 50.8 yr) underwent blood sampling and high-resolution chest computed tomography (HRCT) scanning in an ongoing cohort study; 72 consented to bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsies. Twenty-seven healthy individuals were used as control subjects., Measurements and Main Results: Eleven of 75 at-risk subjects (14%) had evidence of interstitial changes by HRCT, whereas 35.2% had abnormalities on transbronchial biopsies. No differences were noted in inflammatory cells in BAL between at-risk individuals and control subjects. At-risk subjects had increased herpesvirus DNA in cell-free BAL and evidence of herpesvirus antigen expression in alveolar epithelial cells (AECs), which correlated with expression of endoplasmic reticulum stress markers in AECs. Peripheral blood mononuclear cell and AEC telomere length were shorter in at-risk individuals than healthy control subjects. The minor allele frequency of the Muc5B rs35705950 promoter polymorphism was increased in at-risk subjects. Levels of several plasma biomarkers differed between at-risk subjects and control subjects, and correlated with abnormal HRCT scans., Conclusions: Evidence of lung parenchymal remodeling and epithelial dysfunction was identified in asymptomatic individuals at risk for FIP. Together, these findings offer new insights into the early pathogenesis of idiopathic interstitial pneumonia and provide an ongoing opportunity to characterize presymptomatic abnormalities that predict progression to clinical disease.

Aquaporin 11 (AQP11) is a newly described member of the protein family of transport channels. AQP11 associates with the endoplasmic reticulum (ER) and is highly expressed in proximal tubular epithelial cells in the kidney. Previously, we identified and characterized a recessive mutation of the highly conserved Cys227 to Ser227 in mouse AQP11 that caused proximal tubule (PT) injury and kidney failure in mutant mice. The current study revealed induction of ER stress, unfolded protein response, and apoptosis as molecular mechanisms of this PT injury. Cys227Ser mutation interfered with maintenance of AQP11 oligomeric structure. AQP11 is abundantly expressed in the S1 PT segment, a site of major renal glucose flux, and Aqp11 mutant mice developed PT-specific mitochondrial injury. Glucose increased AQP11 protein expression in wild-type kidney and upregulation of AQP11 expression by glucose in vitro was prevented by phlorizin, an inhibitor of sodium-dependent glucose transport across PT. Total AQP11 levels in heterozygotes were higher than in wild-type mice but were not further increased in response to glucose. In Aqp11 insufficient PT cells, glucose potentiated increases in reactive oxygen species (ROS) production. ROS production was also elevated in Aqp11 mutation carriers. Phenotypically normal mice heterozygous for the Aqp11 mutation repeatedly treated with glucose showed increased blood urea nitrogen levels that were prevented by the antioxidant sulforaphane or by phlorizin. Our results indicate an important role for AQP11 to prevent glucose-induced oxidative stress in proximal tubules.

Rationale: Alveolar epithelial cells (AECs) play central roles in the response to lung injury and the pathogenesis of pulmonary fibrosis., Objectives: We aimed to determine the role of β-catenin in alveolar epithelium during bleomycin-induced lung fibrosis., Methods: Genetically modified mice were developed to selectively delete β-catenin in AECs and were crossed to cell fate reporter mice that express β-galactosidase (βgal) in cells of AEC lineage. Mice were given intratracheal bleomycin (0.04 units) and assessed for AEC death, inflammation, lung injury, and fibrotic remodeling. Mouse lung epithelial cells (MLE12) with small interfering RNA knockdown of β-catenin underwent evaluation for wound closure, proliferation, and bleomycin-induced cytotoxicity., Measurements and Main Results: Increased β-catenin expression was noted in lung parenchyma after bleomycin. Mice with selective deletion of β-catenin in AECs had greater AEC death at 1 week after bleomycin, followed by increased numbers of fibroblasts and enhanced lung fibrosis as determined by semiquantitative histological scoring and total collagen content. However, no differences in lung inflammation or protein levels in bronchoalveolar lavage were noted. In vitro, β-catenin-deficient AECs showed increased bleomycin-induced cytotoxicity as well as reduced proliferation and impaired wound closure. Consistent with these findings, mice with AEC β-catenin deficiency showed delayed recovery after bleomycin., Conclusions: β-Catenin in the alveolar epithelium protects against bleomycin-induced fibrosis. Our studies suggest that AEC survival and wound healing are enhanced through β-catenin-dependent mechanisms. Activation of the developmentally important β-catenin pathway in AECs appears to contribute to epithelial repair after epithelial injury.

The mechanisms by which chronic inflammatory lung diseases, particularly chronic obstructive pulmonary disease, confer enhanced risk for lung cancer are not well-defined. To investigate whether nuclear factor (NF)-κB, a key mediator of immune and inflammatory responses, provides an interface between persistent lung inflammation and carcinogenesis, we utilized tetracycline-inducible transgenic mice expressing constitutively active IκB kinase β in airway epithelium (IKTA (IKKβ trans-activated) mice). Intraperitoneal injection of ethyl carbamate (urethane), or 3-methylcholanthrene (MCA) and butylated hydroxytoluene (BHT) was used to induce lung tumorigenesis. Doxycycline-treated IKTA mice developed chronic airway inflammation and markedly increased numbers of lung tumors in response to urethane, even when transgene expression (and therefore epithelial NF-κB activation) was begun after exposure to carcinogen. Studies using a separate tumor initiator/promoter model (MCA+BHT) indicated that NF-κB functions as an independent tumor promoter. Enhanced tumor formation in IKTA mice was preceded by increased proliferation and reduced apoptosis of alveolar epithelium, resulting in increased formation of premalignant lesions. Investigation of inflammatory cells in lungs of IKTA mice revealed a substantial increase in macrophages and lymphocytes, including functional CD4+/CD25+/FoxP3+ regulatory T lymphocytes (Tregs). Importantly, Treg depletion using repetitive injections of anti-CD25 antibodies limited excessive tumor formation in IKTA mice. At 6 weeks following urethane injection, antibody-mediated Treg depletion in IKTA mice reduced the number of premalignant lesions in the lungs in association with an increase in CD8 lymphocytes. Thus, persistent NF-κB signaling in airway epithelium facilitates carcinogenesis by sculpting the immune/inflammatory environment in the lungs.

The incidence of idiopathic pulmonary fibrosis (IPF) increases with age. The mechanisms that underlie the age-dependent risk for IPF are unknown. Based on studies that suggest an association of IPF and γherpesvirus infection, we infected young (2-3 mo) and old (≥18 mo) C57BL/6 mice with the murine γherpesvirus 68. Acute murine γherpesvirus 68 infection in aging mice resulted in severe pneumonitis and fibrosis compared with young animals. Progressive clinical deterioration and lung fibrosis in the late chronic phase of infection was observed exclusively in old mice with diminution of tidal volume. Infected aging mice showed higher expression of transforming growth factor-β during the acute phase of infection. In addition, aging, infected mice showed elevation of proinflammatory cytokines and the fibrocyte recruitment chemokine, CXCL12, in bronchoalveolar lavage. Analyses of lytic virus infection and virus reactivation indicate that old mice were able to control chronic infection and elicit antivirus immune responses. However, old, infected mice showed a significant increase in apoptotic responses determined by in situ terminal deoxynucleotidyl transferase dUTP nick end labeling assay, levels of caspase-3, and expression of the proapoptotitc molecule, Bcl-2 interacting mediator. Apoptosis of type II lung epithelial cells in aging lungs was accompanied by up-regulation of endoplasmic reticulum stress marker, binding immunoglobulin protein, and splicing of X-box-binding protein 1. These results indicate that the aging lung is more susceptible to injury and fibrosis associated with endoplasmic reticulum stress, apoptosis of type II lung epithelial cells, and activation of profibrotic pathways.

There are a variety of oral and topical pharmaceutical agents for the treatment of osteoarthritis. To date there is no pharmacologic agent proved to prevent disease progression. This article focuses primarily on the medications used for symptomatic relief and palliation of pain. The article reviews the medications' mechanisms of action and the available efficacy literature, as well as indications, contraindications, and common adverse effects., (Copyright © 2012 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Since recent evidence indicates a requirement for epithelial nuclear factor (NF)-κB signaling in lung tumorigenesis, we investigated the impact of the NF-κB inhibitor bortezomib on lung tumor promotion and growth. We used an experimental model in which wild-type mice or mice expressing an NF-κB reporter received intraperitoneal urethane (1 g/kg) followed by twice weekly bortezomib (1 mg/kg) during distinct periods of tumor initiation/progression. Mice were serially assessed for lung NF-κB activation, inflammation and carcinogenesis. Short-term proteasome inhibition with bortezomib did not impact tumor formation but retarded the growth of established lung tumors in mice via effects on cell proliferation. In contrast, long-term treatment with bortezomib resulted in significantly increased lung tumor number and size. This tumor-promoting effect of prolonged bortezomib treatment was associated with perpetuation of urethane-induced inflammation and chronic upregulation of interleukin-1β and proinflammatory C-X-C motif chemokine ligands (CXCL) 1 and 2 in the lungs. In addition to airway epithelium, bortezomib inhibited NF-κB in pulmonary macrophages in vivo, presenting a possible mechanism of tumor amplification. In this regard, RAW264.7 macrophages exposed to bortezomib showed increased expression of interleukin-1β, CXCL1 and CXCL2. In conclusion, although short-term bortezomib may exert some beneficial effects, prolonged NF-κB inhibition accelerates chemical lung carcinogenesis by perpetuating carcinogen-induced inflammation. Inhibition of NF-κB in pulmonary macrophages appears to play an important role in this adverse process.

Expression of mutant surfactant protein C (SFTPC) results in endoplasmic reticulum (ER) stress in type II alveolar epithelial cells (AECs). AECs have been implicated as a source of lung fibroblasts via epithelial-to-mesenchymal transition (EMT); therefore, we investigated whether ER stress contributes to EMT as a possible mechanism for fibrotic remodeling. ER stress was induced by tunicamyin administration or stable expression of mutant (L188Q) SFTPC in type II AEC lines. Both tunicamycin treatment and mutant SFTPC expression induced ER stress and the unfolded protein response. With tunicamycin or mutant SFTPC expression, phase contrast imaging revealed a change to a fibroblast-like appearance. During ER stress, expression of epithelial markers E-cadherin and Zonula occludens-1 decreased while expression of mesenchymal markers S100A4 and α-smooth muscle actin increased. Following induction of ER stress, we found activation of a number of pathways, including MAPK, Smad, β-catenin, and Src kinase. Using specific inhibitors, the combination of a Smad2/3 inhibitor (SB431542) and a Src kinase inhibitor (PP2) blocked EMT with maintenance of epithelial appearance and epithelial marker expression. Similar results were noted with siRNA targeting Smad2 and Src kinase. Together, these studies reveal that induction of ER stress leads to EMT in lung epithelial cells, suggesting possible cross-talk between Smad and Src kinase pathways. Dissecting pathways involved in ER stress-induced EMT may lead to new treatment strategies to limit fibrosis.

Evidence of endoplasmic reticulum (ER) stress has been found in lungs of patients with familial and sporadic idiopathic pulmonary fibrosis. We tested whether ER stress causes or exacerbates lung fibrosis by (i) conditional expression of a mutant form of surfactant protein C (L188Q SFTPC) found in familial interstitial pneumonia and (ii) intratracheal treatment with the protein misfolding agent tunicamycin. We developed transgenic mice expressing L188Q SFTPC exclusively in type II alveolar epithelium by using the Tet-On system. Expression of L188Q SFTPC induced ER stress, as determined by increased expression of heavy-chain Ig binding protein (BiP) and splicing of X-box binding protein 1 (XBP1) mRNA, but no lung fibrosis was identified in the absence of a second profibrotic stimulus. After intratracheal bleomycin, L188Q SFTPC-expressing mice developed exaggerated lung fibrosis and reduced static lung compliance compared with controls. Bleomycin-treated L188Q SFTPC mice also demonstrated increased apoptosis of alveolar epithelial cells and greater numbers of fibroblasts in the lungs. With a complementary model, intratracheal tunicamycin treatment failed to induce lung remodeling yet resulted in augmentation of bleomycin-induced fibrosis. These data support the concept that ER stress produces a dysfunctional epithelial cell phenotype that facilitates fibrotic remodeling. ER stress pathways may serve as important therapeutic targets in idiopathic pulmonary fibrosis.

Pharmaceutical treatments for radiculopathy include opioid, antiinflammatory (steroidal and nonsteroidal), neuromodulating, topical, and adjuvant treatments. These medications act locally, peripherally, or centrally on the neural axis. This article reviews the history of medication use for radiculopathy and the available literature along with the breadth of current treatment and indications., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Thymosin-alpha1 (Talpha1) is indicated for the treatment of certain viral infections, including hepatitis B and C, and cancers, such as melanoma. In this paper, the fusion genes encoding human serum albumin (HSA) and Talpha1 with (rHSA-L-Talpha1) and without a linker peptide (rHSA-Talpha1) were constructed and overexpressed in P. pastoris. Through the process of ion interaction chromatography (Q-Sepharose F.F), hydrophobic interaction chromatography (Phenyl Sepharose HP) and affinity chromatography (Blue Sepharose F.F), the purity of fusion proteins was greater than 97%. In contrast to the reactivity of normal spleen cells to Con A, the data of in vitro murine spleen lymphocytes proliferation experiment suggested that spleen cells achieved a higher degree of T cell maturation after rHSA-L-Talpha1, rHSA-Talpha1 and Talpha1 treatments, respectively. Moreover, rHSA-L-Talpha1, rHSA-Talpha1 and Talpha1 can also antagonize dexamethasone-induced apoptosis of thymocyte sub-populations. In hydrocortisone-induced immunosuppression mice (in vivo experiments), after subcutaneous injections with two fusion proteins and Talpha1 for seven consecutive days, the net increment of body weight, the spleen index and the thymus index were significantly improved. Simultaneously, the increase in SOD level and the decrease in MDA level in plasma were observed. The pharmacokinetic data of rHSA-L-Talpha1 and rHSA-Talpha1 administered in rats showed an improved pharmacokinetic profile with a conspicuous prolonged half life. The analysis of bioactivity and pharmacokinetics suggested that fusion proteins rHSA-L-Talpha1 and rHSA-Talpha1 were new drug candidates.

Objective: Development of new methods, ELISA and immunostrip test, for the diagnosis of nasopharyngeal carcinoma., Methods: The engineering purified antigens coat plate or absorb on nitrocellulose filter. The plate and diagnostic strips carrying antigens were used for detection of IgG antibody in the sera from nasopharyngeal carcinoma patients and outpatients patients., Results: 127 cases sera from nasopharyngeal carcinoma patients were parallel detected TK/IgG antibody by ELISA and immunostrips. The TK/IgG antibody are all positive in the 127 cases of nasopharyngeal carcinoma patients. 55 cases show positive by ELISA, 58 cases positive by immunostrips in 247cases sera from outpatient. The antibody positive rate to early antigen p54 lower then to TK. Conclusion ELISA and imuunostrips are sensitive and specific means for detection of the IgG antibody to TK of EBV and the diagnosis of nasopharyngeal carcinoma.

We investigated whether nuclear factor kappa B (NF-kappaB), which exhibits a regulated pattern of activity during murine mammary gland development, plays an important role during lactation and involution, when milk production ceases and the gland undergoes apoptosis and re-modeling. We generated a doxycycline inducible transgenic mouse model to activate NF-kappaB specifically in the mammary epithelium through expression of a constitutively active form of IKK2, the upstream kinase in the classical NF-kappaB signaling cascade. We found that activation of NF-kappaB during involution resulted in a more rapid reduction in milk levels and increased cleavage of caspase-3, an indicator of apoptosis. We also found that activation of NF-kappaB during lactation with no additional involution signals had a similar effect. The observation that NF-kappaB is a key regulator of milk production led us to investigate the role of NF-kappaB during mastitis, an infection of the mammary gland in which milk loss is observed. Mammary gland injection of E. coli LPS resulted in activation of NF-kappaB and milk loss during lactation. This milk loss was decreased by selective inhibition of NF-kappaB in mammary epithelium. Together, our data reveal that activation of NF-kappaB leads to milk clearance in the lactating mammary gland. Therefore, targeting of NF-kappaB signaling may prove therapeutic during mastitis in humans and could be beneficial for the dairy industry, where such infections have a major economic impact.

Nuclear factor kappa B (NF-kappa B) is a critical transcription factor for the production of many inflammatory cytokines. It is activated in the airway epithelium of human asthmatics and in mice after allergic stimulation. To examine the role of NF-kappa B activation in allergic inflammation, the authors generated transgenic mouse lines that allowed for the inducible stimulation of NF-kappa B in airway epithelial cells. After allergic sensitization with ovalbumin and alum, mice were challenged daily with ovalbumin aerosols and NF-kappa B was activated in airway epithelium by administration of doxycycline. Enhancement of airway epithelial NF-kappa B expression alone did not lead to increased airway responsiveness to methacholine. However, induction of epithelial NF-kappa B during allergic inflammation caused airway hyperresponsiveness, increased airway neutrophilic and lymphocytic inflammation and goblet cell hyperplasia. Accompanying the exaggerated inflammation was an increase in the cytokines granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-15, and KC. Interestingly, the counter regulatory interleukin, IL-10, was suppressed by NF-kappa B activation. The epithelial NF-kappa B dependent modulation of these cytokines provides a plausible explanation for the increased inflammation seen with overexpression of NF-kappa B. Modulation of airway epithelial NF-kappa B activation enhances the airway hyperresponsiveness and mucus secretion found in the mouse lung during allergic inflammation. NF-kappa B represents a potential target for pharmacologic intervention in human asthma.

Background: The treatment of critical burn patients involves fluid resuscitation, homeostasis, prevention of infection, support and maintenance of organ functions, nutritional support, and wound repair. Correct management of these problems is a fierce challenge facing burn clinicians. This report presents a critical burn patient with obstinate hyperglycemia and septic shock from pan-drug-resistant strains., Case Report: A 41-year-old female with a 96% total body surface area (TBSA) burn developed a series of severe complications during the course of treatment, including rare obstinate hyperglycemia and septic shock from pan-drug-resistant Acinetobacter baumanii. Several aspects of the applied treatment are emphasized: an immediate effort to close the wound, the appropriate use of antibiotics, and the extraordinarily large amounts of insulin for intensive therapy to control blood sugar., Conclusions: The critical burn patient developed a series of severe complications during the course of treatment. Correct management of these complications is crucial to success in the treatment of such patients.

Angiotensin II is critically involved in skin wound healing, but the underlying mechanism remains unclear. This study investigated the effect of angiotensin II on type I collagen gene activation in human dermal fibroblasts and the possible mechanism involved. Angiotensin II stimulated the mRNA and protein expression of type I collagen and TGF-beta1. Effects were abolished by the angiotensin AT1 receptor antagonist ZD7155 but not by the AT2 blocker PD123319. Blockade of TGF-beta1 markedly inhibited angiotensin II-induced type I collagen gene expression. Activator protein-1 (AP-1) decoy ODNs transfection suppressed angiotensin II-induced TGF-beta1 expression, and also, diminished type I collagen expression. These data indicated that angiotensin II induces collagen gene activation in human dermal fibroblasts through an AT1-mediated AP-1/TGF-beta1 signaling pathway.

This research was set up in response to new European legislation to identify cost-effective treatment for removal of steroid estrogens from effluent. This study aimed to compare estrogen removal of two types of granular activated carbon: virgin (F400) and reactivated (C401) carbon. Rapid, small-scale column tests were conducted with a total bed volume of 24.9 cm3 over three columns, and analysis was carried out using high-performance liquid chromatography. Results demonstrated that C401 performed more efficiently with greater than or equal to 81% estrogen removal in wastewater compared to F400 which produced greater than or equal to 65% estrogen removal. Estrogen removal can be affected by competitive adsorption from natural organic matter present in wastewater. In addition, the physical properties of each carbon had the potential to influence adsorption differently, thus resulting in the observed varied adsorption capability of the two carbons.

Objective: To summarize the clinical experience in repair of deep burn and traumatic wounds with combined transplantation of different types of pedicled skin flaps in lower extremities., Methods: Two hundred and thirty-six patients with 271 deep wounds in lower extremities after burn or trauma were repaired with muscular skin flaps, local fascial flaps and island flaps with vascular pedicle (more than 20 types) in our department from Jan. 1998 to Sept. 2008., Results: Complete necrosis of skin flaps occurred in 1 case, congestion and necrosis over the edge of skin flaps occurred in 3 cases, which were healed after grafting, and other skin flaps survived well with soft texture. Skin flaps were too bulky in 26 cases, among them 17 cases were thinned, and the appearance of other skin flaps were satisfactory. In 68 patients with functional region injury were recovered to certain extent without contracture., Conclusions: Skin flaps with pedicles, multiple transplantations if necessary, can repair deep wounds satisfactorily in lower extremities after deep burn or trauma injury.

Pseudomonas aeruginosa pneumonia usually results from a deficit of the innate immune system. To investigate whether inflammatory signalling by airway epithelial cells provides a pivotal line of defence against P. aeruginosa infection, we utilized two separate lines of inducible transgenic mice that express a constitutive activator of the nuclear factor kappa-B (NF-kappaB) pathway (IKTA) or a dominant inhibitor of NF-kappaB (DNTA) in airway epithelial cells. Compared with control mice, IKTA mice showed an enhanced host response to P. aeruginosa infection with greater neutrophil influx into the lungs, increased expression of Glu-Leu-Arg-positive (ELR(+)) CXC chemokines macrophage inflammatory protein-2 and keratinocyte chemoattractant (KC), superior bacterial clearance and improved survival at 24 h after infection. Neutrophil depletion abrogated the improvement in host defence identified in IKTA mice. In contrast, DNTA mice showed impaired responses to P. aeruginosa infection with higher bacterial colony counts in the lungs, decreased neutrophilic lung inflammation and lower levels of KC in lung lavage fluid. DNTA mice given recombinant KC at the time of P. aeruginosa infection demonstrated improved neutrophil recruitment to the lungs and enhanced bacterial clearance. Our data indicate that the NF-kappaB pathway in airway epithelial cells plays an essential role in defence against P. aeruginosa through generation of CXC chemokines and recruitment of neutrophils.

HBV genome replication intermediates blocked at early stages of minus strand synthesis have been identified in a study on circulating DNA and RNA during short-term lamivudine therapy. This suggested that the inhibition of HBV replication processes in the liver are mirrored in the blood. Levels of circulating HBV mRNA remained largely unaffected. Here we followed therapy with two patients (patients 1 and 2) up to stages without apparent replication. As in the earlier study, DNA segments produced successively during replication were used as targets for quantitative PCR: X (early minus strand), C (completed minus strand), and preC (nascent plus strand). Corresponding RNA was quantified by RT/PCR. Polyadenylated viral RNA were assayed as full-length (f) and as truncated (tr) RNAs. Blocked X-region intermediates persisted for about one year. After a period of undetectable HBV DNA viral replication resumed in patient 1 because of the emergence of drug-resistant mutants and in patient 2 because of the discontinuation of therapy. In the former case, X-region intermediates reappeared first, then C- and, finally, preC-region intermediates. Stopping therapy, in contrast, led to a simultaneous reappearance of all three types of intermediates. At low replication levels or its absence, trRNA represented the only polyadenylated viral RNA. Apparently, HBV serum nucleic acid markers allow a study of replication and transcription separately. Specifically, it is concluded (1) that PCR assays for monitoring lamivudine therapy must target the X-gene region and (2) that in the absence of HBV replication, trRNA may constitute a serum marker for HBV expression.

Recent evidence suggests that dysfunctional type II alveolar epithelial cells (AECs) contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Based on the hypothesis that disease-causing mutations in surfactant protein C (SFTPC) provide an important paradigm for studying IPF, we investigated a potential mechanism of AEC dysfunction suggested to result from mutant SFTPC expression: induction of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). We evaluated biopsies from 23 IPF patients (including 3 family members with L188Q SFTPC mutations, 10 individuals with familial interstitial pneumonia without SFTPC mutations, and 10 individuals with sporadic IPF) and sections from 10 control lungs. After demonstrating UPR activation in cultured A549 cells expressing mutant SFTPC, we identified prominent expression of UPR markers in AECs in the lungs of patients with SFTPC mutation-associated fibrosis. In individuals with familial interstitial pneumonia without SFTPC mutations and patients with sporadic IPF, we also found UPR activation selectively in AECs lining areas of fibrotic remodeling. Because herpesviruses are found frequently in IPF lungs and can induce ER stress, we investigated expression of viral proteins in lung biopsies. Herpesvirus protein expression was found in AECs from 15/23 IPF patients and colocalized with UPR markers in AECs from these patients. ER stress and UPR activation are found in the alveolar epithelium in patients with IPF and could contribute to disease progression. Activation of these pathways may result from altered surfactant protein processing or chronic herpesvirus infection.

Aim: To sum up the recent 30-year experience in the prevention and treatment of gastrointestinal dysfunction in severe burn patients, and propose practicable guidelines for the prevention and treatment of gastrointestinal (GI) dysfunction., Methods: From 1980 to 2007, a total of 219 patients with large area and extraordinarily large area burns (LAB) were admitted, who were classified into three stages according the therapeutic protocols used at the time: Stage 1 from 1980 to 1989, stage 2 from 1990 to 1995, and stage 3 from 1996 to 2007. The occurrence and mortality of GI dysfunction in patients of the three stages were calculated and the main causes were analyzed., Results: The occurrence of stress ulcer in patients with LAB was 8.6% in stage 1, which was significantly lower than that in stage 1 (P < 0.05). No massive hemorrhage from severe stress ulcer and enterogenic infections occurred in stages 2 and 3. The occurrence of abdominal distension and stress ulcer and the mortality in stage 3 patients with extraordinarily LAB was 7.1%, 21.4% and 28.5%, respectively, which were significantly lower than those in stage 1 patients (P < 0.05 or P < 0.01), and the occurrence of stress ulcer was also significantly lower than that in stage 2 patients (P < 0.05)., Conclusion: Comprehensive fluid resuscitation, early excision of necrotic tissue, staged food ingestion, and administration of specific nutrients are essential strategies for preventing gastrointestinal complications and lowering mortality in severely burned patients.

Chronic inflammation is linked to carcinogenesis in several organ systems. In the lungs, NF-kappaB, a central effector of inflammatory responses, is frequently activated in non-small-cell lung cancer, but its role in tumor promotion has not been studied. Several lines of evidence indicate that ethyl carbamate (urethane)-induced lung tumor formation, a prototypical mouse model of multistage lung carcinogenesis, is potentiated by inflammation. We found that mouse strains susceptible to lung tumor formation (FVB, BALB/c) exhibited early NF-kappaB activation and inflammation in the lungs after urethane treatment. However, a resistant strain (C57B6) failed to activate NF-kappaB or induce lung inflammation. In FVB mice, we identified urethane-induced NF-kappaB activation in airway epithelium, as well as type II alveolar epithelial cells and macrophages. Using an inducible transgenic mouse model (FVB strain) to express a dominant inhibitor of NF-kappaB specifically in airway epithelial cells, we found that urethane-induced lung inflammation was blocked and tumor formation was reduced by >50%. Selective NF-kappaB inhibition resulted in increased apoptosis of airway epithelial cells at 2 weeks after urethane treatment in association with a marked reduction of Bcl-2 expression. These studies indicate that NF-kappaB signaling in airway epithelium is integral to tumorigenesis in the urethane model and identify the NF-kappaB pathway as a potential target for chemoprevention of lung cancer.