Synergistic detoxification efficiency and mechanism of triclocarban degradation by a bacterial consortium in the liver-gut-microbiota axis of zebrafish (Danio rerio).

Triclocarban (TCC), an emerging organic contaminant, poses a potential threat to human health with long-term exposure. Here, Rhodococcus rhodochrous BX2 and Pseudomonas sp. LY-1 were utilized to degrade TCC at environmental related concentrations for enhancing TCC biodegradation and investigating whether the toxicity of intermediate metabolites is lower than that of the parent compound. The results demonstrated that the bacterial consortium could degrade TCC by 82.0% within 7 days. The calculated 96 h LC50 for TCC, as well as its main degradation product 3,4-Dichloroaniline (DCA) were 0.134 mg/L and 1.318 mg/L respectively. Biodegradation also alleviated histopathological lesions induced by TCC in zebrafish liver and gut tissues. Liver transcriptome analysis revealed that biodegradation weakened differential expression of genes involved in disrupted immune regulation and lipid metabolism caused by TCC, verified through RT-qPCR analysis and measurement of related enzyme activities and protein contents. 16 S rRNA sequencing indicated that exposure to TCC led to gut microbial dysbiosis, which was efficiently improved through TCC biodegradation, resulting in decreased relative abundances of major pathogens. Overall, this study evaluated potential environmental risks associated with biodegradation of TCC and explored possible biodetoxification mechanisms, providing a theoretical foundation for efficient and harmless bioremediation of environmental pollutants.

Pretreatment mortality risk prediction model in patients with polymyositis/dermatomyositis-associated interstitial lung disease.

OBJECTIVES: Risk prediction for patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) is challenging due to heterogeneity in the disease course. We aimed to develop a mortality risk prediction model for PM/DM-ILD. METHODS: This prognostic study analysed patients with PM/DM-ILD admitted to Nanjing Drum Hospital from 2016 to 2021. The primary outcome was mortality within 1 year. We used a least absolute shrinkage and selection operator (LASSO) logistic regression model to identify predictive laboratory indicators. These indicators were used to create a laboratory risk score, and we developed a mortality risk prediction model by incorporating clinical factors. The evaluation of model performance encompassed discrimination, calibration, clinical utility and practical application for risk prediction and prognosis. RESULTS: Overall, 418 patients with PM/DM-ILD were enrolled and randomly divided into development (n=282) and validation (n=136) cohorts. LASSO logistic regression identified four optimal features in the development cohort, forming a laboratory risk score: C reactive protein, lactate dehydrogenase, CD3+CD4+ T cell counts and PO2/FiO2. The final prediction model integrated age, arthralgia, anti-melanoma differentiation-associated gene 5 antibody status, high-resolution CT pattern and the laboratory risk score. The prediction model exhibited robust discrimination (area under the receiver operating characteristic: 0.869, 95% CI 0.811 to 0.910), excellent calibration and valuable clinical utility. Patients were categorised into three risk groups with distinct mortality rates. The internal validation, sensitivity analyses and comparative assessments against previous models further confirmed the robustness of the prediction model. CONCLUSIONS: We developed and validated an evidence-based mortality risk prediction model with simple, readily accessible clinical variables in patients with PM/DM-ILD, which may inform clinical decision-making.

Six Years of Complaints Issued by Patients at a Laser Treatment Center in a Plastic Surgery Hospital.

Background: Patient complaints can provide valuable feedback regarding the objective deficiencies of medical services. There are few studies on the complaints of patients receiving photoelectric therapy, so this study aims to understand the expectations and requirements of patients by analyzing the complaints of patients receiving photoelectric therapy. Methods: The complaints of patients who underwent photoelectric therapy were retrospectively examined. Authors plan to analyze treatment items, complaint contents, appeals, time trend regarding the number of complaints, and economic compensation. Results: Fifty-four patients were involved in the study in total, and all of them were included. According to the standardized coding classification of complaints by Reader et al., the number of clinical, management and relationship complaints were 36 (59.02%), 14 (22.95%), and 11 (18.03%), respectively. These were divided among the categories of quality (31.15%), safety (27.87%), institutional issues (22.95%), communication (8.20%), and humaneness/caring (9.84%); with the most common subcategories involving treatment (31.15%) and safety incidents (24.59%). The patients' demands involved 20 cases (32.26%) requesting a refund of their medical expenses, 16 (25.81%) issuing a warning, 15 (24.19%) requesting compensation for loss, 10 (16.13%) requiring free repair or consultation, and 1 (1.61%) demanding an apology. Eventually, financial compensation was provided to the patients in eight of the cases. At a significance level of P = 0.05, even if the number of annual complaints increased over time, the increasing trend was not significant. Conclusions: Patient complaints in photoelectric therapy were most commonly clinical in nature. Specifically, quality and safety concerns are the main complaints.

Neurons on tape: Automated Tape Collecting Ultramicrotomy-mediated volume EM for targeting neuropathology.

In this chapter, we review Automated Tape Collecting Ultramicrotomy (ATUM), which, among other array tomography methods, substantially simplified large-scale volume electron microscopy (vEM) projects. vEM reveals biological structures at nanometer resolution in three dimensions and resolves ambiguities of two-dimensional representations. However, as the structures of interest-like disease hallmarks emerging from neuropathology-are often rare but the field of view is small, this can easily turn a vEM project into a needle in a haystack problem. One solution for this is correlated light and electron microscopy (CLEM), providing tissue context, dynamic and molecular features before switching to targeted vEM to hone in on the object's ultrastructure. This requires precise coordinate transfer between the two imaging modalities (e.g., by micro computed tomography), especially for block face vEM which relies on physical destruction of sections. With array tomography methods, serial ultrathin sections are collected into a tissue library, thus allowing storage of precious samples like human biopsies and enabling repetitive imaging at different resolution levels for an SEM-based search strategy. For this, ATUM has been developed to reliably collect serial ultrathin sections via a conveyor belt onto a plastic tape that is later mounted onto silicon wafers for serial scanning EM (SEM). The ATUM-SEM procedure is highly modular and can be divided into sample preparation, serial ultramicrotomy onto tape, mounting, serial image acquisition-after which the acquired image stacks can be used for analysis. Here, we describe the steps of this workflow and how ATUM-SEM enables targeting and high resolution imaging of specific structures. ATUM-SEM is widely applicable. To illustrate this, we exemplify the approach by reconstructions of focal pathology in an Alzheimer mouse model and CLEM of a specific cortical synapse.

Spatial Transcriptomics-correlated Electron Microscopy maps transcriptional and ultrastructural responses to brain injury.

Understanding the complexity of cellular function within a tissue necessitates the combination of multiple phenotypic readouts. Here, we developed a method that links spatially-resolved gene expression of single cells with their ultrastructural morphology by integrating multiplexed error-robust fluorescence in situ hybridization (MERFISH) and large area volume electron microscopy (EM) on adjacent tissue sections. Using this method, we characterized in situ ultrastructural and transcriptional responses of glial cells and infiltrating T-cells after demyelinating brain injury in male mice. We identified a population of lipid-loaded "foamy" microglia located in the center of remyelinating lesion, as well as rare interferon-responsive microglia, oligodendrocytes, and astrocytes that co-localized with T-cells. We validated our findings using immunocytochemistry and lipid staining-coupled single-cell RNA sequencing. Finally, by integrating these datasets, we detected correlations between full-transcriptome gene expression and ultrastructural features of microglia. Our results offer an integrative view of the spatial, ultrastructural, and transcriptional reorganization of single cells after demyelinating brain injury.

Diagnostic finding on high-resolution computed tomography (HRCT) predicts a good response to pirfenidone in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a debilitating condition, with a life expectancy of 2 to 5 years after diagnosis. Pirfenidone is a drug that has been shown to reduce the decline in forced vital capacity (FVC). We sought to identify whether different patterns on high-resolution computed tomography (HRCT) have different clinical effects through a retrospective comparison of baseline values and changes in pulmonary function tests (PFTs) after treatment with pirfenidone. We retrospectively analyzed data from IPF patients treated with pirfenidone at Nanjing Drum Tower Hospital in Jiangsu Province, China. According to the HRCT pattern, the patients were divided into usual interstitial pneumonitis (UIP) and possible UIP groups. Baseline clinical characteristics and changes every 6 months in the PFTs during the follow-up period were compared between the 2 groups. A total of 65 consecutive patients were enrolled. According to the HRCT pattern, patients were clustered into the UIP group (n = 46) and possible UIP group (n = 19). No difference was observed in the baseline PFTs ratio between the 2 groups. The FVC values of the 2 groups were not significantly different at the initial treatment and at 6 and 12 months after pirfenidone treatment (P = .081, 0.099, and 0.236, respectively). The improvement in % diffusion capacity of the lung for carbon monoxide (%DLCO) was higher in the possible UIP group after 6 and 12 months of pirfenidone treatment (P = .149, 0.026, and 0.025, respectively). The annual decrease in FVC was not significantly different between the 2 groups, and the annual decrease in %DLCO in the UIP group was significantly higher than that in patients with the possible UIP type (-7.767 ±â€…12.797 vs 0.342 ±â€…20.358, P < .05). These results indicate that patients with IPF with a possible UIP pattern on HRCT showed indications of a good response to pirfenidone.

Genome Functional Analysis of the Psychrotrophic Lignin-Degrading Bacterium Arthrobacter sp. C2 and the Role of DyP in Catalyzing Lignin Degradation.

In the cold regions of China, lignin-rich corn straw accumulates at high levels due to low temperatures. The application of psychrotrophic lignin-degrading bacteria should be an effective means of overcoming the low-temperature limit for lignin degradation and promoting the utilization of corn straw. However, this application is limited by the lack of suitable strains for decomposition of lignin; furthermore, the metabolic mechanism of psychrotrophic lignin-degrading bacteria is unclear. Here, the whole genome of the psychrotrophic lignin-degrading bacterium Arthrobacter sp. C2, isolated in our previous work, was sequenced. Comparative genomics revealed that C2 contained unique genes related to lignin degradation and low-temperature adaptability. DyP may participate in lignin degradation and may be a cold-adapted enzyme. Moreover, DyP was proven to catalyze lignin Cα-Cß bond cleavage. Deletion and complementation of the DyP gene verified its ability to catalyze the first-step reaction of lignin degradation. Comparative transcriptomic analysis revealed that the transcriptional expression of the DyP gene was upregulated, and the genetic compensation mechanism allowed C2ΔDyP to degrade lignin, which provided novel insights into the survival strategy of the psychrotrophic mutant strain C2ΔdyP. This study improved our understanding of the metabolic mechanism of psychrotrophic lignin-degrading bacteria and provided potential application options for energy-saving production using cold-adapted lignin-degrading enzymes.

A Retrospective Analysis of Outcome in Melanoma Differentiation-Associated Gene 5-Related Interstitial Lung Disease Treated with Tofacitinib or Tacrolimus.

OBJECTIVE: The efficacy of tofacitinib (TOF) in the early diagnosis of melanoma differentiation-associated gene 5 (MDA5)-related interstitial lung disease (ILD) has been described. However, whether TOF exposure is associated with a reduced 1-year mortality rate remains undetermined. METHODS: Patients diagnosed with MDA5-ILD receiving TOF or tacrolimus (TAC) treatment were included. A Cox proportional hazards model, which was adjusted for age, sex, smoking history, anti-MDA5 antibody titers, and concurrent use of other steroid-sparing agents, was performed to compare all-cause mortality and to investigate the risk factors predicting 1-year mortality rates in the 2 treatment groups. RESULTS: During the study period, 26 patients were treated with TOF and 35 were treated with TAC. The 6-month (38.5% vs 62.9%; P = 0.03) and 1-year (44.0% vs 65.7%; P = 0.03) mortality rates in the TOF group were significantly lower than those in the TAC group. There were 13 patients diagnosed with rapidly progressive ILD (RP-ILD) in the TOF group and 22 in the TAC group. The majority of deaths occurred in patients with RP-ILD. The 6-month (76.9% vs 95.5%; P = 0.02) and 1-year (84.6% vs 100.0%; P = 0.02) mortality rates of patients with RP-ILD in the TOF group were also lower than those in the TAC group, respectively. The adjusted model showed that TOF exposure was associated with a lower risk for 1-year mortality (hazard ratio 0.44, 95% CI 0.20-0.96; P = 0.04). However, the incidence of adverse events (73.1% vs 74.3%; P > 0.99) and medication discontinuation rates (23.1% vs 14.3%; P = 0.50) in the TOF and TAC groups were similar, respectively. CONCLUSION: Our observational study showed that TOF use might have a potential effect on improving the outcomes of MDA5-ILD. Future clinical trials are needed to assess the long-term efficacy and tolerability of TOF.

Insight into biofilm-forming patterns: biofilm-forming conditions and dynamic changes in extracellular polymer substances.

The microbial biofilm adheres to the surface of the carrier, which protects the pollutant-degrading bacteria and resists harsh environments; thus, research on biofilm-forming patterns will help promote the application of biofilms in wastewater treatment. Herein, univariate analysis and response surface methodology (RSM) confirmed that glucose and mannose at 3-5 g/L promoted biofilm formation. Notably, the microplate method demonstrated that compared to trivalent cations, divalent cations could more greatly enhance the activity (especially magnesium) of the biofilm matrix, and the period of biofilm formation in the three strains was divided into the following stages: initial attachment (0-10 h), microcolony (10-24 h), maturation (24-48 h), and dispersion (36-72 h). During maturation, large amounts of extracellular polysaccharides (EPs) and extracellular DNA (eDNA) were distributed in the extracellular and intracellular spaces, respectively, as observed by super-resolution structured illumination microscopy (SR-SIM). This study enhances the understanding of the characteristics and patterns of biofilm formation and can facilitate the application of biofilms in wastewater treatment.

Potential and mechanism for bioremediation of papermaking black liquor by a psychrotrophic lignin-degrading bacterium, Arthrobacter sp. C2.

To meet the challenge of bioremediation of black liquor in pulp and paper mills at low temperatures, a psychrotrophic lignin-degrading bacterium was employed in black liquor treatment for the first time. In this study, Arthrobacter sp. C2 exhibited excellent cold adaptability and lignin degradation ability, with a lignin degradation rate of 65.5% and a mineralization rate of 43.9% for 3 g/L lignin at 15 °C. Bioinformatics analysis and multiple experiments confirmed that cold shock protein 1 (Csp1) was the dominant cold regulator of strain C2, and dye-decolorizing peroxidase (DyP) played a crucial role in lignin degradation. Moreover, structural equation modeling (SEM), mRNA monitoring, and phenotypic variation analysis demonstrated that Csp1 not only mediated cold adaptation but also modulated DyP activity by controlling dyp gene expression, thus driving lignin depolymerization for strain C2 at low temperatures. Furthermore, 96.4% of color, 64.2% of chemical oxygen demand (COD), and 100% of nitrate nitrogen (NO3--N) were removed from papermaking black liquor by strain C2 within 15 days at 15 °C. This study provides insights into the association between the cold regulator and catalytic enzyme of psychrotrophic bacteria and offers a feasible alternative strategy for the bioremediation of papermaking black liquor in cold regions.

Efficient conversion of hemicellulose into 2, 3-butanediol by engineered psychrotrophic Raoultella terrigena: mechanism and efficiency.

Low-temperature biorefineries inhibit the multiplication of undesired microorganisms, improve product purity and reduce economic costs. Herein, to improve the 2,3-butanediol (2,3-BD) bioconversion efficiency from hemicellulose, a psychrotrophic hemicellulose-degrading strain Raoultella terrigena HC6 with high ß-xylosidase activity 1520 U/mL was isolated and genetically modified. Xylan (hemicellulose replacement) was depolymerized into xylooligosaccharides (XOS) and xylose by HC6, which were further converted into 2,3-BD. Transcriptomic analysis revealed that ß-xylosidase gene (xynB) and xylose isomerase gene (xylA), which are beneficial for increasing the carbon flux from xylan to 2,3-BD, were significantly upregulated 56.9-fold and 234-fold, respectively. A recombinant strain was constructed by overexpressing xynB in HC6, which obtained 0.389 g/g yield of 2,3-BD from hemicellulose extracted from corn straw at 15 °C. This study proposed a promised strategy for the bioconversion of agricultural waste into 2,3-BD at low temperatures and provides a basis for future efforts in the achievement of carbon neutrality.

Nonsurgical Treatment for Congenital Auricular Deformities: A Systematic Review and Meta-analysis.

BACKGROUND: The effectiveness and safety of non-surgical correction for congenital auricular deformities (CADs) remain unclear owing to a lack of high-level evidence. This systematic review and meta-analysis aimed to estimate the overall success and complication rates of the non-surgical correction for CAD. METHODS: We searched PubMed, Medline, and Cochrane Library for eligible studies. The pooled success and complication rates of non-surgical correction were estimated using a random effects model. Subgroup analyses were performed to compare the success rates between patients treated with splints and molding systems, between those younger and older than 6-weeks, and among those with different types of CADs. RESULTS: The review yielded 14 studies. The pooled success rate of non-surgical treatment was 93% (95% CI: 88%-97%). The success rates with splints and commercialized molding systems were 94% and 92%, respectively. The success rate was higher if non-surgical correction was initiated before age 6 weeks (96% vs. 82%). Prominent ears showed a lower success rate (85%) than other types of CADs (all > 90%). The pooled complication rate was 18% (95% CI: 10%-29%). Complications, including skin wound, irritation, and rash, were mild and easily treatable. CONCLUSION: The non-surgical correction of CADs is highly effective and safe. Splints and molding systems offer similar effectiveness. Non-surgical correction is more beneficial if applied within 6 weeks of birth. Prominent ears have a lower, but still acceptable, success rate compared to other types of CAD. We recommend the early use of non-surgical correction to achieve favorable outcomes. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Efficient vanillin biosynthesis by recombinant lignin-degrading bacterium Arthrobacter sp. C2 and its environmental profile via life cycle assessment.

Vanillin is a natural flavoring agent that is widely used in the bioengineering industry. To enable sustainable development, joint consideration of bacterial performance and negative environmental impacts are critical to vanillin biosynthesis. In this study, a cold shock protein (csp) gene was upregulated for maintaining stable growth in Arthrobacter sp. C2 responding to vanillin and cold stress. Furthermore, the recombinant strain C2 was constructed by simultaneously deleting the xylC gene encoding benzaldehyde dehydrase and overexpressing the pchF gene encoding vanillyl alcohol oxidase and achieved a maximum vanillin productivity of 0.85 mg/g DCW/h with alkaline lignin as the substrate. Finally, this process generated an environmental impact value of 25.05, which was the lowest environmental impact achieved according to life cycle assessment (LCA). Improvement strategies included reducing electricity consumption and replacing chemicals. This study achieved the development of an effective strategy, and future studies should focus on precise vanillin biosynthesis methods for large-scale application.

Using New Autologous Tissue Filler Improved Nasolabial Folds-Single-Armed Pilot Study.

OBJECTIVE: To evaluate the clinical efficacy and safety of the new autologous tissue filler derived from autologous skin and hairs for correction of nasolabial folds. MATERIALS AND METHODS: The new injectable soft tissue filler is prepared from autologous fibroblasts and keratin gel. A total of 40 patients were enrolled in this single-armed pilot study, all of them received the new filler injection treatment for correction nasolabial folds. Following up with the patients, collection of their clinical features, including photographs, satisfaction, and information on adverse events at the 1st, 3rd, 6th, 12th, and 24th months after injection. The clinical efficacy of each patient was evaluated by masked evaluators and independent expert panels, based on the Wrinkle Severity Rating Scale (WSRS) at different time points after the injection. RESULTS: Thirty-two patients completed the 24-months follow-up, obtaining at least 93.8% improvement, and 75% of them had significantly improved. Base on the self-satisfaction assessment (SSA) indicated that all of them were satisfied with the results. No adverse effects of filler injection treatment were observed during the follow-up. CONCLUSIONS: The combination of autologous keratin and fibroblasts as a new tissue engineering soft tissue filler has shown safety and long-term efficiency in correcting nasolabial folds, with high satisfaction and desirable result. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Albumin-to-alkaline phosphatase ratio: A novel prognostic index for patients with driver mutation-negative advanced non-small cell lung cancer.

INTRODUCTION: Albumin-to-Alkaline Phosphatase Ratio (AAPR), a novel developed prognostic index for cancers. Chemotherapy was the only method for driver mutation-negative advanced non-small cell lung cancer (DANSCLC). OBJECTIVES: To evaluate the clinical significance of AAPR in these patients. METHODS: We retrospectively reviewed 167 DANSCLCs and 58 healthy controls. Associations of clinicopathological characteristics and survival analysis were conducted. RESULTS: Significantly decreased AAPR level was uncovered in DANSCLC patients compared to healthy controls. The correlation analysis revealed that the low AAPR level in DANSCLCs was correlated with poor differentiation (P = .024). Cox regression analysis showed that N stage, M stage, and different levels of AAPR were the independent risk factors of PFS and OS. The median PFS and OS survival ratio in patients with high and low AAPR level was, respectively, 17 months and 8 months, and 23 months and 13 months. The AUC of AAPR for both PFS and OS were higher than that of albumin and alkaline phosphatase (p < 0.05). The low AAPR was associated with much shorter PFS and OS than the high AAPR (mPFS: 8 vs. 25 months; mOS: 12 vs. 36 months). In the AP cohort, the low AAPR group experienced significantly shorter PFS and OS than the high AAPR (mPFS: 7 vs. 25 months; mOS: 12 vs. 36 months). Meanwhile, there was no significance in lung squamous cell carcinoma (LUSC) patients and GP regimens cohort. CONCLUSION: AAPR significantly decreased in patients with DANSCLC, and it affects the prognosis of patients with DANSCLC and is a biomarker for DANSCLCs prognosis and treatment choice.

A long-term retrospective study of patients with biopsy-proven cryptogenic organizing pneumonia.

Cryptogenic organizing pneumonia (COP) is characterized by good response to corticosteroids, but frequent relapses after reduction or cessation of treatment are noted. The incidence, risk factors of relapse, and long-term outcomes of patients with COP remain undetermined. Patients with COP from September 2010 to December 2017 were enrolled. Hospital and office records were used as data sources. Clinical information, lab examinations, chest radiographs, treatment courses, and follow-up data were collected. Relapse group was defined as worsening of clinical manifestations in combination with progression of radiographic abnormalities in the absence of identified causes. Eighty-seven patients with COP were enrolled. Of them, 73 patients were treated with corticosteroids with relapse rate yielding 31.5% (23 of 73). Eleven patients were treated with macrolides and none of them relapsed. Fever was more common (65.2% vs. 32.0%, p = 0.004), C-reactive protein (CRP) was higher (31.5 ± 39.4 mg/L vs. 17.5 ± 32.2 mg/L, p = 0.038), and diffusion capacity for carbon monoxide (DLCO) % predicted was lower (45.9 ± 14.2% vs. 57.6 ± 18.5%, p = 0.050) in relapse group compared to nonrelapse group. Four patients who presented with organizing pneumonia (OP) as the first manifestation were ultimately diagnosed with OP secondary to autoimmune disease in follow-up. We showed relapse was common in COP patients treated with corticosteroids, but the prognosis was favorable. Fever, elevated CRP, and a reduced DLCO were related to relapse. As OP may not always be cryptogenic, a careful follow-up should be programmed to diagnose the underlying systemic disease.

Risk factors of relapse in pulmonary sarcoidosis treated with corticosteroids.

OBJECTIVE: To evaluate the incidence and risk factors of relapse in pulmonary sarcoidosis treated with corticosteroids. METHODS: Medical records of patients with pulmonary sarcoidosis were retrospectively reviewed. Clinical features, chest radiographs, pulmonary function tests, and treatment information were collected. The starting point was the date of diagnosis. Clinical relapse was defined as chest high-resolution computed tomography (HRCT) showing radiographic progression in combination of worsening of clinical symptoms to warrant retreatment following a decrease in dose or discontinuation of corticosteroids, without alternative causes such as infections, heart failure, or pulmonary embolism. Non-relapse was defined as remission of clinical symptoms and chest abnormalities, or clinical syndrome improvement with retention or stability of radiographic abnormalities after corticosteroids were withdrawn for at least 6 months. The primary endpoint was the occurrence of relapse. RESULTS: Two hundred three patients with newly biopsy-proven pulmonary sarcoidosis were enrolled over a 7-year period. Among them, 96 patients received corticosteroids therapy. Relapse occurred in 30 patients with the relapse rate yielding 30/96 (31.25%). After adjustment, multivariate analysis showed that smoking history (HR = 3.674 95% CI 1.573-8.581, P = 0.003) and increased percentages of circulating neutrophils (> 70%) (HR = 2.211, 95% CI 1.073-4.557, P = 0.032) were the significant predictors of relapse in pulmonary sarcoidosis treated with corticosteroids. CONCLUSIONS: This study provided useful information that the relapse and associated risk factors should be taken into considerations when determining treatment strategies for patients with pulmonary sarcoidosis.

Heparan sulfate D-glucosamine 3-O-sulfotransferase 3B1 is a novel regulator of transforming growth factor-beta-mediated epithelial-to-mesenchymal transition and regulated by miR-218 in nonsmall cell lung cancer.

BACKGROUND: Due to high metastasis and recurrence rate. Recent studies indicated that epithelial-to-mesenchymal transition (EMT) was involved in the progression and metastasis in cancer. Some reports also indicate that HS3ST3B1 played a role in angiogenesis and the proliferation of cancer cells. In this study, we aim to investigate its role in non-small cell lung cancer (NSCLC) . MATERIALS AND METHODS: All cell lines were purchased from ATCC and cultured in our central lab. RT-PCR was performed to study the expession of HS3ST3B1 in tumors and matched normal tissues. Western-blot was used to investigate the expession of HS3ST3B1 in cell lines. We also used luciferase report system to confirm the regulation of HS3ST3B1 by miR-218 in cells. RESULTS: In this study, we found that HS3ST3B1 was significantly upregulated in NSCLC tissues compared with matched normal tissues (P = 0.02). Its expression was also up-regulated in mesenchymal phenotype of NSCLC cell lines compared with epithelial phenotype (P < 0.05). When TGF-ß was applied to induce the epithelial phenotype to mesenchymal phenotype, it was upregulated compared with previous epithelial cell lines. When HS3ST3B1 was knocked down by specific small interfering RNA in the mesenchymal phenotype, mesenchymal phenotype was transformed to epithelial phenotype. Moreover, we also found that it could be targeted by miR-218 in NSCLC. CONCLUSION: These findings indicate that HS3ST3B1 is a novel regulator of TGF-beta-mediated EMT and is regulated by miR-218 in NSCLC.

Down-regulation of long non-coding RNA AFAP1-AS1 inhibits tumor cell growth and invasion in lung adenocarcinoma.

An increasing number of deregulated long non-coding RNAs (lncRNA) have been implicated in cancer in humans, suggesting that lncRNAs may be involved in tumorigenesis or tumor progression. In previous investigations, lncRNA, AFAP1-AS1 has been found to be associated with several cancers, including nasopharyngeal carcinoma, lung cancer and esophageal adenocarcinoma. However, the function of AFAP1-AS1 in lung cancer has not been reported. In our present study, we found that AFAP1-AS1 was overexpressed in lung adenocarcinoma and associated with survival time. The low expression of AFAP1-AS1 was an independent predictor for disease-free survival in patients with lung adenocarcinoma. Additionally, we transfected AFAP1-AS1 siRNA into H1975 and HCC827, both lung adenocarcinoma cancer cells, and found that cell growth was suppressed, apoptosis induced and invasion inhibited. Taken together, AFAP1-AS1 down-regulation exerts growth suppression and apoptosis induction in lung adenocarcinoma cells, suggested it may participate in turmorigenesis and be a therapeutic target for treating lung adenocarcinoma in future.