Reduced miR-513a-5p expression in COPD may regulate airway mucous cell hyperplasia through TFR1-dependent signaling.

Airway mucous cell metaplasia and mucous hypersecretion is one of the key characteristic pathophysiological status of chronic obstructive pulmonary disease (COPD). micro(mi)RNAs are acknowledged as non-encoding RNA molecules playing important roles in gene expression regulation. In this study, we searched the Gene Expression Omnibus (GEO) database for the differentially expressed miRNAs between COPD and non-COPD controls with bioinformatics analysis. Finally, we focused on miR-513a-5p and investigated the potential mechanism by which miR-513a-5p regulates airway mucous hypersecretion and goblet cell metaplasia. A dual-luciferase reporter assay was then showing that miR-513a-5p targeted the 3'-UTR of TFR1 and inhibited its expression in vitro. In vivo transfection demonstrated that TFR1 downregulation partially blocked MUC5AC hypersecretion and goblet cell hyperplasia in COPD model rats. In vitro study, CSE increased the intracellular expression and secretion of MUC5AC by BEAS-2B branchial epithelial cells in the BEAS-2B cell and THP-1 cell coculture system. Coculture with either miR-513a-5p mimic-pretreated or TFR1-deficient THP-1 cells attenuated intracellular MUC5AC expression in BEAS-2B cells exposed to CSE. ELISA demonstrated that transfection of TFR1 siRNA or pretreatment with miR-513a-5p mimic reduced the secretion of inflammatory factors that are responsible for airway goblet cell hyperplasia, such as IL-1ß, IL-13, and IL-17, by THP-1 cells after CSE stimulation. Our findings supported that miR-513a-5p/TFR1 signaling axis might activate macrophages as well as promote airway inflammation and airway mucous cell hyperplasia in COPD.

KRAS and BRAF Mutation Rates and Survival Outcomes in Colorectal Cancer in an Ethnically Diverse Patient Cohort.

KRAS and BRAF mutation rates in colorectal cancer (CRC) reported from various mono-ethnic studies vary amongst different ethnic groups. However, these differences in mutation rates may not be statistically significant or may be due to differences in environmental and/or laboratory factors across countries rather than racial genetic differences. Here, we compare the KRAS/BRAF mutation rates and survival outcomes in CRC between ethnic groups at a single institution. We also investigate the contributions of genetic, environmental, and laboratory factors to the variations in KRAS/BRAF mutation rates reported from different countries. Clinicopathological data from 453 ethnically diverse patients with CRC were retrospectively analyzed at Liverpool Hospital, NSW Australia (2014-2016). KRAS/BRAF mutations were detected using real-time PCR (Therascreen kits from Qiagen). Mismatch repair (MMR) status was determined using immunohistochemical staining. Four ethnic groups were analyzed: Caucasian, Middle Eastern, Asian, and South American. Overall survival data were available for 406 patients. There was no significant difference in KRAS mutation rates between Caucasians (41.1%), Middle Easterners (47.9%), Asians (44.8%), and South Americans (25%) (p = 0.34). BRAF mutation rates differed significantly between races (p = 0.025), with Caucasians having the highest rates (13.5%) and Middle Easterners the lowest (0%). A secondary analysis in which Caucasians were divided into three subgroups showed that ethnic grouping correlated significantly with KRAS mutation rate (p = 0.009), with central and eastern Europeans having the highest rates (58.3%). There were no significant differences in overall survival (OS) or disease-free survival (DFS) between the four races. The similarity in KRAS mutation rates across races raises the possibility that the differences in KRAS mutation rates reported from various countries may either not be statistically significant or may be due to environmental and/or laboratory factors rather than underlying racial genetic differences. In contrast, we verified that BRAF mutation rates differ significantly between races, suggesting racial genetic differences may be responsible for the discrepant BRAF mutation rates reported from different countries.

Development and Validation of a Machine Learning-Based Model Using CT Radiomics for Predicting Immune Checkpoint Inhibitor-related Pneumonitis in Patients With NSCLC Receiving Anti-PD1 Immunotherapy: A Multicenter Retrospective CaseControl Study.

RATIONALE AND OBJECTIVES: This study aimed to develop and evaluate a radiomics-based model combined with clinical and qualitative radiological (semantic feature [SF]) features to predict immune checkpoint inhibitor-related pneumonitis (CIP) in patients with non-small cell lung cancer (NSCLC) treated with programmed cell death protein 1 inhibitors. MATERIALS AND METHODS: This was a multicenter retrospective casecontrol study conducted from January 1, 2018, to December 31, 2022, at three centers. Patients with NSCLC treated with anti-PD1 were enrolled and randomly divided into two groups (7:3): training (n = 95) and validation (n = 39). Logistic regression (LR) and support vector machine (SVM) algorithms were used to transform features into the models. RESULTS: The study comprised 134 participants from three independent centers (male, 114/134, 85%; mean [±standard deviation] age, 63.92 [±7.9] years). The radiomics score (RS) models built based on the LR and SVM algorithms could accurately predict CIP (area under the receiver operating characteristics curve [AUC], 0.860 [0.780, 0.939] and 0.861 [0.781, 0.941], respectively). The AUCs for the RS-clinic-SF combined model were 0.903 (0.839, 0.967) and 0.826 (0.688, 0.964) in the training and validation cohorts, respectively. Decision curve analysis showed that the combined models achieved high clinical net benefit across the majority of the range of reasonable threshold probabilities. CONCLUSION: This study demonstrated that the combined model constructed by the identified features of RS, clinical features, and SF has the potential to precisely predict CIP. The RS-clinic-SF combined model has the potential to be used more widely as a practical tool for the noninvasive prediction of CIP to support individualized treatment planning.

E2F1-initiated transcription of PRSS22 promotes breast cancer metastasis by cleaving ANXA1 and activating FPR2/ERK signaling pathway.

Breast cancer (BC) is the most common malignant tumor in women worldwide. Metastasis is the main cause of BC-related death. The specific mechanism underlying BC metastasis remains obscure. Recently, PRSS22 was discovered to be involved in tumor development, however, its detailed biological function and regulatory mechanism in BC are unclear. Here, we characterized that PRSS22 expression is upregulated in BC tissues compared with non-tumorous breast tissues. Dual luciferase assays, bioinformatics analyses and chromatin immunoprecipitation (ChIP) assays indicated that transcription factor E2F1 directly binds to the PRSS22 promoter region and activates its transcription. Functionally, upregulation of PRSS22 promoted invasion and metastasis of BC cells in vitro and in vivo, whereas knockdown of PRSS22 inhibited its function. Mechanistically, the combination of PRSS22 and ANXA1 protein in BC cells was first screened by protein mass spectrometry analysis, and then confirmed by co-immunoprecipitation (Co-IP) and western blot assays. Co-overexpression of PRSS22 and ANXA1 could promote BC cell migration and invasion. We further demonstrated that PRSS22 promotes the cleavage of ANXA1 and in turn generates an N-terminal peptide, which initiates the FPR2/ERK signaling axis to increase BC aggressiveness.

Association between environmental exposure to perchlorate, nitrate, and thiocyanate and serum α-Klotho levels among adults from the National Health and nutrition examination survey (2007-2014).

BACKGROUND & AIMS: Aging is a pathophysiological process driven by a diverse set of complex biological processes, and environmental pollution plays an important role in this process. This study aimed to explore the association between serum α-Klotho levels and urinary perchlorate, nitrate, and thiocyanate levels. METHODS: This secondary dataset analysis included 4875 participants (mean age, 57.69 year; male, 49.58%; non-Hispanic White, 47.67%) from the US National Health and Nutrition Examination Survey (2007-2014). Enzyme-linked immunosorbent assay was used to quantify α-Klotho levels, and ion chromatography coupled with electrospray tandem mass spectrometry was used to quantify thiocyanate, nitrate, and perchlorate levels. Multivariate linear regression models were applied to estimate the association between perchlorate, nitrate, and thiocyanate levels and serum α-Klotho levels. RESULTS: Urinary thiocyanate levels were negatively associated with α-Klotho levels (ß = - 0.006; 95% confidence interval, - 0.010 to - 0.003; P = 0.0004) after adjusting for age, sex, body mass index, race, alcohol consumption, estimated glomerular filtration rate, underlying disease, physical activity, smoking status, usual energy intake, and urinary creatinine and serum cotinine levels and mutual adjustment of urinary perchlorate, urinary nitrate, and urinary thiocyanate levels. The α-Klotho level in participants in the highest quartile was higher by 50.567 ng/mL (ß = 50.567; 95% confidence interval, 14.407 to 86.726; P = 0.009) than that in participants in the lowest quartile of urinary perchlorate. A linear relationship was observed between urinary thiocyanate and α-Klotho levels. CONCLUSIONS: Urinary thiocyanate levels were negatively associated with serum α-Klotho levels. Urinary thiocyanate should be further investigated as a potential mediator of aging and age-related diseases.

[Distribution Characteristics and Source Apportionment of Perfluoroalkyl Substances in Surface Soils of the Northeast Tibetan Plateau].

Surface soil samples collected at 18 sites from the northeast Tibetan Plateau were used to analyze perfluoroalkyl substances (PFASs) via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to study the concentration levels and sources of PFASs. The results showed that 11 PFASs were detected in the soil, and the ω(Σ11PFASs) ranged from 0.043-1.573 ng·g-1 with an average concentration of 0.398 ng·g-1. PFBA displayed the highest concentration level with a mean content of 0.164 ng·g-1, whereas PFHxA was at the lowest level (0.005 ng·g-1). The concentrations of the other PFASs were similar to each other (0.011-0.057 ng·g-1). Generally, PFASs contents in the west and north were higher than that in the southeast, and the alpine condensation effect existed for PFBA. The principal component analysis showed that PFASs in surface soils in the northeast Tibetan Plateau region mainly originated from the atmospheric transport of PFASs and their precursors. Few areas were affected by direct emissions of point source pollution, and the main sources were the industrial production of metals/minerals and other human activities.

[Clinical Value of Cystatin C-Based Estimated Glomerular Filtration Rate in Assessing Short-Term Mortality in Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure Treated with Artificial Liver Support System].

OBJECTIVE: To evaluate the predictive value of using cystatin c-based estimated glomerular filtration rate (eGFR-CysC) in assessing the prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) patients treated with artificial liver support system (ALSS). METHODS: A total of 364 HBV-ACLF inpatients treated with ALSS at our hospital were enrolled retrospectively in the study. The patients were divided into the survival group ( n=269) and non-survival group ( n=95) according to mortality within 28 d, and their clinical information and laboratory data were analyzed for assessing short-term prognostic values. RESULTS: Multivariate Cox regression analysis identified eGFR-CysC as one of the independent risk factors associated with mortality within 28 days in HBV-ACLF patients (the hazard ratio=0.987; 95% confidence interval, 0.979-0.996, P=0.003). In addition, baseline eGFR-CysC was negatively correlated with the model for end-stage liver disease (MELD) score ( r=-0.439, P<0.001), MELD plus sodium (MELD-Na) score ( r=-0.481, P<0.001) and Chronic Liver Failure Consortium ACLF (CLIF-C ACLF) score ( r=-0.340, P<0.001). Receiver operating characteristic (ROC) curve analysis showed area under the curve ( AUC) of eGFR-CysC were 0.639, 0.697, 0.716, 0.749 and the best cut-off value were 70.620, 67.525, 61.725, 64.685 mL/(min·1.73 m 2), respectively, for baseline value and the first, second, and third treatment with ALSS. CONCLUSION: eGFR-CysC could be used to assist clinical assessment of short-term mortality in HBV-ACLF patients treated with ALSS, and has better clinical application value for dynamic monitoring.

Meigs' syndrome caused by granulosa cell tumor accompanied with intrathoracic lesions: A case report.

BACKGROUND: Meigs' syndrome is regarded as a benign ovarian tumor accompanied by pleural effusion and ascites, both of which resolve after removal of the tumor. Patients often seek treatment in the Department of Respiratory and Critical Care Medicine or other internal medicine departments due to symptoms caused by ascites or hydrothorax. Here, we report a rare case of Meigs' syndrome caused by granulosa cell tumor accompanied with intrathoracic lesions. CASE SUMMARY: A 52-year-old women was admitted to the Department of Respiratory and Critical Care Medicine due to coughing and expectoration accompanied with shortness of breath. Chest X-ray and chest computed tomography showed a modest volume of pleural fluid with pleural thickening in the right lung. The carbohydrate antigen 125 (CA125) concentration was 150.8 U/mL (normal, 0-35 U/mL) and no tumor cells were observed in pleural fluid. Nodules and a neoplasm with a fish meat-like appearance in the parietal pleura and nodules with a 'string of beads'-like appearance in the diaphragm were found by thoracoscopic examination. Furthermore, pelvic magnetic resonance revealed a pelvic mass measuring about 11.6 cm × 10.0 cm × 12.4 cm with heterogeneous signal intensity and multiple hypointense separations. Total abdominal hysterectomy, bilateral adnexectomy, and separation of pelvic adhesion were performed under general anesthesia. The pathology results showed granulosa cell tumor. At the 2-mo follow-up after the surgery, the hydrothorax subsided, and the CA125 level returned to normal. CONCLUSION: For postmenopausal women with unexplained hydrothorax and elevated CA125, in addition to being suspected of having gynecological malignancy, Meigs' syndrome should be considered.

Correlation between income and non-alcoholic fatty liver disease in a Chinese population.

OBJECTIVE: The aim of the study was to analyze the correlation between income and non-alcoholic fatty liver disease (NAFLD) in a Chinese population. METHOD: subjects were divided into three groups according to liver fat content (LFC). (1) normal: LFC < 9.15%, 197 cases; (2) low LFC: LFC 9.15-20%, 532 cases; and (3) high LFC: LFC > 20%, 201 cases. Participants' clinical and social background were collected, including a routine fasting test to assess the relevant indices. Intergroup differences were compared on 1-way ANOVA, to analyze the relation between income and each index on Pearson correlation, and independent factors for LFC were identified on binary logistic regression. RESULTS: (1) In retired persons, prevalence of NAFLD was greater in females (81.2%) than males (75%), but fell with age: the highest prevalence was between 40 and 49 years of age (87.5%), and the lowest above 70 years (68%). (2) Income correlated positively with triglyceride and serum uric acid levels and LFC (P < 0.05) and negatively with alanine aminotransferase (P = 0.01). (3) As income increased from level I to V, prevalence of NAFLD increased progressively (P < 0.05). In the study, LFC was taken as the dependent variable, and the traditional NAFLD risk factors and income level (I-V) were taken as independent variables. Income emerged as an independent risk factor for NAFLD. Risk in group V was 1.964-fold higher than in group I. CONCLUSION: Prevalence of NAFLD was closely related to socio-economic level. Demographic risk factors include female gender, age 40-49 years, and monthly income > 5,000 RMB. Thus, if income is increased without improving educational level and health awareness, NAFLD prevalence will rise.

Establishment of novel long-term cultures from EpCAM positive and negative circulating tumour cells from patients with metastatic gastroesophageal cancer.

Circulating tumour cell (CTC) enumeration and profiling has been established as a valuable clinical tool in many solid malignancies. A key challenge in CTC research is the limited number of cells available for study. Ex vivo CTC culture permits expansion of these rare cell populations for detailed characterisation, functional assays including drug sensitivity testing, and investigation of the pathobiology of metastases. We report for the first time the establishment and characterisation of two continuous CTC lines from patients with gastroesophageal cancer. The two cell lines (designated UWG01CTC and UWG02CTC) demonstrated rapid tumorigenic growth in immunodeficient mice and exhibit distinct genotypic and phenotypic profiles which are consistent with the tumours of origin. UWG02CTC exhibits an EpCAM+, cytokeratin+, CD44+ phenotype, while UWG01CTC, which was derived from a patient with metastatic neuroendocrine cancer, displays an EpCAM-, weak cytokeratin phenotype, with strong expression of neuroendocrine markers. Further, the two cell lines show distinct differences in drug and radiation sensitivity which match differential cancer-associated gene expression pathways. This is strong evidence implicating EpCAM negative CTCs in metastasis. These novel, well characterised, long-term CTC cell lines from gastroesophageal cancer will facilitate ongoing research into metastasis and the discovery of therapeutic targets.

Assessment of serum Tim-3 and Gal-9 levels in predicting the risk of infection after kidney transplantation.

Infection remains a major cause of morbidity and mortality after kidney transplantation (KT). Reliable biomarkers to predict post-transplant infection are lacking. We investigated the predictive performance of pre- and post-transplant levels of T-cell immunoglobulin and mucin domain-3 (Tim-3) and Galectin-9 (Gal-9), two pleiotropic immunomodulatory molecules, in early identification of infection. Serum Tim-3 and Gal-9 were paired measured before and 30 days after transplantation (PTD 30) in 95 KT recipients (KTRs). The decline rates of Tim-3 and Gal-9 were calculated relative to pre-transplant levels. KTRs with infection history had significantly higher levels of PTD 30 Tim-3 and Gal-9, and slower decrease rates of Gal-9 compared to non-infected recipients, while no difference was observed between two groups regarding pre-transplant levels. The AUCs for predicting 1-year post-transplant infection were 0.653 and 0.711 for post-transplant Tim-3 and Gal-9, 0.664 and 0.670 for relative Tim-3 and Gal-9, respectively. After adjusting for potential confounders, PTD 30 Tim-3, Gal-9 and relative Gal-9 remained as independent risk factors for post-transplant infection. Our results suggested that PTD 30 Tim-3 and Gal-9 and relative decrease of Gal-9 were promising predictors for identifying KTRs with high risk of infection, while pre-transplant Tim-3 and Gal-9 showed no predictive power to infection.

Comparison of urine and blood NGAL for early prediction of delayed graft function in adult kidney transplant recipients: a meta-analysis of observational studies.

BACKGROUND: Neutrophil gelatinase-assoicated lipocalin (NGAL) appears to be a promising proximal tubular injury biomarker for early prediction of delayed graft function (DGF) in kidney transplant recipients. However, its predictive values in urine and blood were varied among different studies. Here, we performed the meta-analysis to compare the predictive values of urine NGAL (uNGAL) and blood NGAL (bNGAL) for DGF in adult kidney transplant recipients. METHODS: We systematically searched Medline, Cochrane library and Embase for relevant studies from inception to May 2018. The summary receiver operating characteristic (SROC) curves, the pooled sensitivity, specificity and diagnostic odds ratio (DOR) were used to evaluate the prognostic performance of uNGAL and bNGAL for the identification of DGF. RESULTS: A total of 1036 patients from 14 eligible studies were included in the analysis. 8 studies focused on NGAL in urine and 6 reported NGAL in serum or plasma. The composite area under the ROC (AUC) for 24 h uNGAL was 0.91 (95% CI, 0.89-0.94) and the overall DOR for 24 h uNGAL was 24.17(95% CI, 9.94-58.75) with a sensitivity of 0.88 (95% CI, 0.75-0.94) and a specificity of 0.81 (95% CI, 0.68-0.89). The composite AUC for 24 h bNGAL was 0.95 (95% CI, 0.93-0.97) and the overall DOR for 24 h bNGAL was 43.11 (95% CI, 16.43-113.12) with a sensitivity of 0.91 (95% CI, 0.81-0.96) and a specificity of 0.86 (95% CI, 0.78-0.92). CONCLUSIONS: Urine and serum/plasma NGAL were valuable biomarkers for early identification of DGF in kidney transplantation. In addition, the bNGAL was superior to uNGAL in early prediction of DGF.

Clot Histopathology in Ischemic Stroke with Infective Endocarditis.

BACKGROUND: Endovascular thrombectomy (EVT) has shown efficacy in acute ischemic stroke (AIS) patients with infective endocarditis (IE). The possibility to undertake advanced histopathological clot analysis following EVT offers a new avenue to establish the etiological basis of the stroke - which is often labelled "cryptogenic." In this paper, we present our findings from four consecutive patients with IE who underwent EVT following an AIS at our tertiary referral comprehensive stroke centre. METHODS: Comprehensive histopathological analysis of clot retrieved after EVT, including morphology, was undertaken. RESULTS: The consistent observation was the presence of dense paucicellular fibrinoid material mixed/interspersed with clusters of bacterial cocci. This clot morphology may be specific to septic embolus due to IE unlike incidental bacteraemia and could possibly explain the refractoriness of such clots to systemic thrombolysis. CONCLUSION: Detailed morphological and histopathological analysis of EVT-retrieved clots including Gram staining can assist in etiological classification of the clot. Understanding the composition of the clot may be of clinical value in early diagnostics and mapping treatment planning in IE.

Enhanced IL-6/phosphorylated STAT3 signaling is related to the imbalance of circulating T follicular helper/T follicular regulatory cells in patients with rheumatoid arthritis.

BACKGROUND: Follicular helper T (Tfh) cells are specialized in helping B lymphocytes, which play a central role in autoimmune diseases that have a major B cell component, such as in rheumatoid arthritis (RA). Follicular regulatory T (Tfr) cells control the over-activation of Tfh and B cells in germinal centers. Dysregulation of Tfh cells and Tfr cells has been reported to be involved in the pathogenesis of some autoimmune diseases. However, the balance of Tfh and Tfr cells, and their roles in the development and progression of RA are still not clear. METHODS: In this study, we enrolled 44 patients with RA (20 patients with active RA and 24 patients with inactive RA) and 20 healthy controls, and analyzed the frequencies of circulating Tfh and Tfr cells, expression of programmed death-1 (PD-1), inducible co-stimulator (ICOS), intracellular IL-21, and pSTAT3 in Tfh cells, and serum levels of IL-6. The correlation among these parameters and that of Tfh or Tfr cells with disease activity were also analyzed. RESULTS: Patients with RA (especially active RA) had higher frequencies of Tfh cells, but lower percentages of Tfr cells, thereby resulting in elevated ratios of Tfh/Tfr. Expression levels of PD-1 and IL-21 in Tfh cells were higher in patients with RA than in healthy subjects, while no difference in ICOS expression was observed between patients and controls. Both pSTAT3 expression and serum IL-6 levels increased in patients with RA, and positive correlation between them was observed. Additionally, pSTAT3 expression was positively correlated with Tfh cell frequency. The Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) was negatively correlated with Tfr cell frequency, but was positively correlated with both Tfh/Tfr ratio and PD-1 expression. CONCLUSIONS: Results demonstrated that enhanced IL-6/pSTAT3 signaling may contribute to promotion of Tfh cells, consequently skewing the ratio of Tfh to Tfr cells, which may be crucial for disease progression in RA.

In situ splitting after selective partial portal vein ligation or simultaneous hepatic artery ligation promotes liver regeneration.

This study seeks to compare the impact of selective partial portal vein ligation (PPVL) or the combination of simultaneous hepatic artery ligation (PPVAL) with in situ splitting (ISS) on liver regeneration and injury. Rats were randomized into three groups; namely: selective PVL, PPVL + ISS and PPVAL + ISS. The changes in hepatic hemodynamics, liver regeneration and hepatocytic injury were examined. Blood flow to the left portal branch and the microcirculation of the left median lobe after PPVL or PPVAL was significantly reduced. Liver regeneration of PPVAL + ISS group was more pronounced than that in the PPVL + ISS and PVL groups at 48 and 72 hours as well as 7 d postoperatively. The serum biochemical markers and histopathological examination demonstrated reduced levels of liver injury in the PPVL + ISS group. Injury to hepatocytes was more pronounced with PPVAL + ISS than PVL. HGF, TNF-α and IL-6 expression in the regenerated lobes in both PPVAL + ISS and PPVL + ISS groups increased significantly when compared to the PVL group. We demonstrated that both PPVL + ISS and PPVAL + ISS were effective and feasible means of inducing remnant liver hypertrophy and could serve as a rapid clinical application for qualified patients.

Ex utero intrapartum treatment for giant congenital omphalocele.

BACKGROUND: To determine whether ex utero intrapartum treatment (EXIT) is an appropriate approach for managing fetuses antenatally diagnosed with giant congenital omphaloceles. METHODS: We retrospectively reviewed patients with omphaloceles who underwent either an EXIT procedure or a traditional repair surgery. Basic and clinical parameters including gender, gestational age, birth weight, maternal blood loss, operative times and operative complications were analyzed. During the 6-12-month follow-ups, postoperative complications including bowel obstruction, abdominal infections, postoperative abdominal distension were monitored, and survival rate was analyzed. RESULTS: A total of seven patients underwent the EXIT procedure and 11 patients underwent the traditional postnatal surgery. We found no differences in maternal age, gestational age at diagnosis, gestational age at delivery and birth weight between the two groups. In the EXIT group, the average operation time for mother was 68.3 ± 17.5 minutes and the average maternal blood loss was 233.0 ± 57.7 mL. The operation time in the EXIT group (22.0 ± 4.5 minutes) was shorter than that in the traditional group (35 ± 8.7 minutes), but the length of hospital stay in the EXIT group (20.5 ± 3.1 days) was longer than that in the traditional group (15.7 ± 2.5 days, P < 0.05). During the follow-up, one patient in the EXIT group had an intestinal obstruction, one developed abdominal compartment syndrome and one died in the traditional group. CONCLUSIONS: In our experience, EXIT is a safe and effective procedure for the treatment of giant congenital omphaloceles. However, more experience is needed before this procedure can be widely recommended.

Soluble Tim-3 and Gal-9 are associated with renal allograft dysfunction in kidney transplant recipients: A cross-sectional study.

BACKGROUND: T cell immunoglobulin mucin-3 (Tim-3) has been reported to participate in the regulation of immune response and the induction of allograft tolerance. However, the association between Tim-3 and renal allograft dysfunction is unclear. We studied the expression of cellular and soluble Tim-3 (sTim-3), soluble galectin-9 (sGal-9) and carcinoembryonic antigen-related cell adhesion molecule-1 (sCEACAM-1) in kidney transplantation recipients (KTRs) to explore their roles in allograft dysfunction. METHODS: 96 KTRs (53 with stable graft and 43 with graft dysfunction) and 30 healthy controls (HC) were enrolled. Among the KTRs, 55 used Tacrolimus (TAC) and 41 used Sirolimus (SRL). In the dysfunction group, 29 recipients have undergone graft biopsy and 14 were classified as biopsy-proven rejection (BPR). Cellular Tim-3 was determined by flow cytometry. sTim-3 was determined by ELISA. sGal-9 and sCEACAM-1 were determined by Bio-Plex® suspension array system. RESULTS: KTRs with renal dysfunction showed significantly higher levels of sTim-3 and sGal-9 but similar levels of cellular Tim-3 and sCEACAM-1 compared with stable recipients. Correlation analysis revealed that estimated glomerular filtration rate (eGFR) was negatively associated with sTim-3 and sGal-9. Both BPR and non-BPR groups showed comparable levels of Tim-3, Gal-9 and CEACAM-1. Moreover, SRL group showed significantly higher levels of sCEACAM-1 than TAC and HC groups. CONCLUSIONS: sTim-3 and sGal-9 were promising biomarkers for allograft dysfunction, but unable to differentiate allograft rejection from other causes of renal dysfunction in KTRs. Moreover, long-term administration of sirolimus would up-regulate sCEACAM-1 level, while exert similar regulatory effects on Tim-3 and Gal-9 compared to tacrolimus.

Impact of immunosuppressive drugs on circulating Tfh cells in kidney transplant recipients: A pilot study.

BACKGROUND: T follicular helper cells (Tfh) are recently revealed to be vital in antibody-mediated rejection (AMR) in kidney transplant recipients (KTRs). However, the impact of immunosuppressive drugs on Tfh cells is not fully understood. The purpose of this study was to investigate the variation of Tfh cells phenotypically and functionally in KTRs treated with different immunosuppression regimens. METHODS: We recruited 26 KTRs treated with tacrolimus (TAC) -based regimen, 13 with sirolimus (SRL) -based regimen and 10 healthy controls (HC) in this study. The percentage and absolute number of circulating Tfh cells and the co-expression of Tfh related molecules including inducible costimulatory molecule (ICOS), programmed cell death protein 1 (PD-1), interleukin-21 (IL-21) and signal transducer and activator of transcription 3 (STAT3) were analyzed by flow cytometry, while serum IL-6 was detected by electrochemiluminescence immunoassay. RESULTS: The percentage and absolute number of Tfh cells and the co-expression of PD-1, STAT3 in Tfh cells were significantly higher in TAC group than that in SRL group. While no difference was found in regard to IL-21 and ICOS co-expressed with Tfh cells among three groups. Multiple linear regression analysis results showed that pre-transplant PRA level was the significant confounder affecting the absolute numbers of Tfh and CD4+CXCR5+PD-1+ T cells. In addition, correlation analysis showed that CD4+CXCR5+STAT3+ T cells were positively correlated to Tfh cells. CONCLUSIONS: Our study indicates that sirolimus can suppress the quantity of Tfh cells more significantly than tacrolimus. The higher level of circulating Tfh cells in tacrolimus group might be related to STAT3 signaling.

Metabolic syndrome is independently associated with a mildly reduced estimated glomerular filtration rate: a cross-sectional study.

BACKGROUND: Association between metabolic syndrome (MS) and mildly reduced estimated glomerular filtration rates (eGFRs) remains unclear. Therefore, we aimed to evaluate the association between MS and a mildly reduced eGFR in Chinese adults. METHODS: Anthropometric and biochemical examinations were performed in 2992 individuals. The eGFR was calculated from the creatinine level. MS was defined according to the Adult Treatment Panel III criteria as the presence of three or more risk factors. Mildly reduced eGFR was defined as a value between 60 and 90 mL/min/1.73 m2. Multiple linear regression and multiple logistic regression analysis were used to evaluate association between metabolic syndrome and estimate glomerular filtration rate. RESULTS: After adjusting for several potential confounders, the participants with MS showed a 1.29-fold increased odds ratio for a mildly reduced eGFR compared with those without MS. Additionally, the odds ratios (and 95% confidence intervals (CIs)) for mildly reduced eGFR in participants with elevated triglycerides (TG), decreased high-density lipoprotein (HDL), obesity and elevated fasting blood glucose (FPG) after multivariable adjustment were 1.25 (1.05-1.49), 1.23 (1.03-1.48), 1.22 (1.03-1.45) and 0.64 (0.52-0.78), respectively. The odds ratios (95% CIs) for hyperfiltration in participants with elevated FPG and HbA1c levels after multivariable adjustment were 1.53 (1.30-1.81) and 2.86 (2.00-4.09), respectively. CONCLUSIONS: MS is associated with an increased risk of a mildly reduced eGFR in the Chinese population, and several individual components of MS have different impacts on eGFR levels. MS had dual roles on renal damage. TRIAL REGISTRATION: ChiCTR-TRC- 14005029 . Registered 28 July 2014.

Ultrasmall silver nanoclusters: Highly efficient antibacterial activity and their mechanisms.

Silver materials have been widely used as antimicrobial agents. Notably, silver nanoparticles have emerged as a new generation of nanoproducts for biomedical and environmental applications in recent years. However, ultrasmall silver nanoclusters (NCs) (∼2 nm) have rarely been used to kill bacteria and their antibacterial mechanisms have not yet been fully elucidated. Herein, we studied the antibacterial activities of bifunctional fluorescent DHLA-AgNCs against three types of bacteria. The results showed that DHLA-AgNCs exhibited excellent antibacterial activities against Gram-negative E. coli, which could efficiently inhibit the growth of E. coli DH 5α and E. coli DSM 4230 cells at a concentration of 15 and 10 µg mL-1, respectively. Meanwhile AgNCs demonstrated no apparent antibacterial activity against Gram-positive S. aureus. Then, the antibacterial mechanisms of AgNCs were systematically investigated. We found that AgNCs affected the growth of different E. coli strains in different ways. AgNCs inhibited the growth of E. coli DH 5α mainly through damaging the outer cellular membrane and permeating into the cells, followed by the antibacterial effect of the internalized AgNCs and released silver ions. AgNCs, however, inhibited the growth of E. coli DSM 4230 cells mainly through diffusing into E. coli DSM 4230 cells and damaging their respiratory chain. These results clearly indicated that different bacterial strains (e.g. different E. coli strains) should be taken into consideration in future studies. Our work facilitates further investigation of the design of new antibacterial silver nanomaterials with different sizes.