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.

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.

[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.

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.

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.

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.

The miR-573/apoM/Bcl2A1-dependent signal transduction pathway is essential for hepatocyte apoptosis and hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with an increasing incidence worldwide. Apolipoprotein M (apoM) is a novel apolipoprotein that is mainly expressed in liver and kidney tissues. However, the anti-tumor properties of apoM remain largely unknown. We evaluated the anti-tumor activities and mechanisms of apoM in HCC both in vivo and in vitro. Bioinformatic analysis and luciferase reporter assay results showed that apoM was a potential target of hsa-miR-573 and was downregulated after transfection with hsa-miR-573 mimics. Overexpression of apoM suppressed migration, invasion, and proliferation of hepatoma cells in vitro. Overexpression of hsa-miR-573 in hepatoma cells reduced apoM expression, leading to promotion of the invasion, migration, and proliferation of hepatoma cells in vitro. In addition, hsa-miR-573 markedly promoted growth of xenograft tumors in nude mice with an accompanying reduction in cell apoptosis. ApoM markedly inhibited growth of xenograft tumors in nude mice and promoted cell apoptosis. Moreover, Bcl2A1 mRNA and protein levels were inhibited by apoM overexpression and an increase in apoptosis rate by apoM was markedly compensated by Bcl2A1 overexpression in HepG2 cells. These results provide evidence that hsa-miR-573 promoted tumor growth by inhibition of hepatocyte apoptosis and this pro-tumor effect might be mediated through Bcl2A1 in an apoM-dependent manner. Therefore, our findings may be useful to improve understanding of the critical effects of hsa-miR-573 and apoM in HCC pathogenesis.

ZEB1 expression is correlated with tumor metastasis and reduced prognosis of breast carcinoma in Asian patients.

Tumor metastasis is one of the key events leading to tumor relapse and poor prognosis. Nowadays, increasing evidences demonstrated that ZEB1 was implicated in human carcinogenesis. However, involvement of ZEB1 deregulation in tumorigenesis in Asian patients with breast carcinoma remains elusive. The present study included 102 Asian patients with breast carcinoma treated by surgery from January of 2005 to December of 2006, and the expression of ZEB1 was evaluated by immunohistochemistry. To further assess the prognostic value of ZEB1, Kaplan-Meier curves were constructed. In this study, elevated levels of ZEB1 expression was found in carcinomas with higher aggressive potential. We also correlated expression of ZEB1 with lymph node metastasis (P = 0.021), advanced clinical stage (P = 0.012) in all cases, and high tumor grade (P = 0.047) in invasive ductal carcinoma. Furthermore, our data suggested an elevated level of Ki-67 expression in cases with positive expression of ZEB1. Clinically, reduced overall survival and disease-free survival were observed in cases with positive ZEB1 expression than that in negative cases. Our results correlated ZEB1 with aggressive potentials of breast carcinoma and revealed a possibility for ZEB1 as a prognostic marker in breast carcinoma.

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.

The histopathological spectrum and molecular changes associated with KRAS G12C mutation in non-small cell lung carcinoma.

KRAS G12C is the most common KRAS mutation in non-small cell lung carcinoma (NSCLC), for which targeted therapy has recently been developed. From the 732 cases of NSCLC that underwent next-generation sequencing at the Department of Anatomical Pathology, Liverpool Hospital, between July 2021 and May 2023, we retrieved 83 (11%) consecutive cases of KRAS G12C mutated NSCLC, and analysed their clinical, pathological, and molecular features. Of the 83 cases of KRAS G12C mutated NSCLC, there were 46 (55%) men and 37 (45%) women, with mean age of 72 years. Of the 49 cases with known clinical information, 94% were current or ex-smokers, and 49% were stage IV at diagnosis with median survival of 12 months. Sixty-three percent were histology cases and the remainder were cytology cases. Eighty-two percent were non-mucinous adenocarcinomas, with conventional histology including lepidic, acinar, solid, single cells and micropapillary patterns, and 62% were poorly differentiated. There were five (6%) cases of mucinous adenocarcinoma, one case of pleomorphic carcinoma and one case of high-grade fetal adenocarcinoma. TTF1 was positive in the majority (89%) of cases. Nineteen (23%) cases had TP53 co-mutation, and these cases had trends towards higher PD-L1 expression, poor differentiation, and presentation as stage IV disease, but the differences were not statistically significant. KRAS G12C mutated NSCLCs almost exclusively occurred in smokers and were mostly non-mucinous adenocarcinomas with conventional histological patterns which ranged from well to poorly differentiated. Around a quarter had TP53 co-mutation, the histological impacts and immune profile of which need to be assessed in a larger study.

Anti-inflammatory effects of propofol are mediated by apolipoprotein M in a hepatocyte nuclear factor-1α-dependent manner.

Propofol (2,6-diisopropylphenol) is probably the most widely used intravenous hypnotic agent in daily practice. However, its anti-inflammatory properties have seldom been addressed. In this study, we evaluated the anti-inflammatory activity and mechanisms of propofol on lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro and found that propofol markedly inhibited LPS-induced production of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6, and expression of inducible nitric oxide synthase (iNOS). At the same time, the expression of hepatocyte nuclear factor-1α (HNF-1α) and apolipoprotein M (APOM) was inhibited by treatment with LPS and LPS-induced down-regulation of HNF-1α expression and APOM expression could be compensated by propofol treatment. However, propofol could not compensate LPS-induced down-regulation of APOM expression by treatment with HNF-1α siRNA and the suppressive effect on LPS-induced pro-inflammatory cytokines production by propofol was significantly compensated by treatment with APOM siRNA. These results provide evidence that propofol may first up-regulate APOM expression by enhancing HNF-1α expression and then inhibit pro-inflammatory cytokine production in LPS-stimulated cells. Therefore, our study may be useful in understanding the critical effect of propofol in patients with systemic inflammatory response syndrome.

A new diagnostic scoring system to differentiate Hirschsprung's disease from Hirschsprung's disease-allied disorders in patients with suspected intestinal dysganglionosis.

PURPOSE: To create a simple diagnostic scoring system to differentiate Hirschsprung's disease (HD) from Hirschsprung's disease-allied disorders (HAD) in patients with suspected intestinal dysganglionosis (IDs). METHODS: Between 1998 and 2008, 967 patients with suspected intestinal dysganglionosis underwent surgical treatment at the pediatric surgery department of Tongji Hospital. The diagnosis of HD or HAD was confirmed by postoperative pathological examination. All patients underwent preoperative work-up including barium enema, anorectal manometry, and histochemical acetylcholinesterase staining of rectal mucosa. Known risk factors for IDs were recorded. The predicting score was calculated by summing the scores of the risk factors and three preoperative tests. The sensitivity, specificity, accuracy, positive predictive values, negative predictive values, positive likelihood ratios, and negative likelihood ratios of the predicting score were calculated. The cutoff score for predicting HD was determined using receiver operating characteristic (ROC) analysis. The accuracy of the predicting score was measured by the area under the ROC curve. RESULTS: Failed or delayed passage of meconium, age <3 years and male gender were risk factors associated with HD. The area under the ROC curve of the predicting score was 0.927 (95 % confidence interval, 0.910-0.944). A predicting score of more than 5 was used as a cutoff for predicting HD. The scoring system achieved 83.1 % sensitivity, 89.5 % specificity, and 85.9 % accuracy in predicting HD. CONCLUSION: Patients with a predicting score of more than 5 are more likely to be diagnosed with HD, whereas a score less than 5 are mostly indicative of HAD.

[Spectroscopic study of dilute magnetic semiconductors Zn(1-x) Fe(x)O nanoparticles].

Diluted magnetic semiconductors Zn(1-x) Fe(x)O nanoparticles with different content (x = 0, 0.01, 0.05, 0.10 and 0.20) were successfully synthesized via hydrothermal method. The X-ray diffraction (XRD) shows that the samples are wurtzite structure and metallic Fe or other secondary phases were not found in the samples. The transmission electron microscopy (TEM) shows that the morphology is nanoparticles with good dispersion, and the lattice is clearly visible. Raman scattering spectrum (Raman spectra) shows that E2 (High) mode broadened, shifted towards the high-frequencies side and decreased the peak intensity. Photoluminescence spectra (PL) shows that the peaks moved to lower energy and the photoluminescence intensity was quenched with increasing Fe doping concentration. The ultraviolet-visible spectrophotometry (UV-Vis) indicates that the optical band gap decreased and red shift occured. All the results indicate that Fe3+ ions successfully substituted for Zn2+ and were incorporated into the crystal lattice of ZnO.

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.

[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.

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.

[A meta-analysis of the effect and safety of angiotensin II receptor blockers in treatment of portal hypertension in cirrhotic patients].

OBJECTIVE: To evaluate the efficacy and safety of the angiotensin II receptor blockers (ARB) in reducing portal hypertension (PHT) in patients with cirrhosis. METHODS: PubMed, EMBASE, Web of Science, The Cochrane Central Register of Controlled Trials, Chinese Biomedical Database, Chinese Journals Full-text Database and WanFang Digital Journal Full-text database were searched. Statistical analysis was performed by meta-analysis using RevMan4.2 software. RESULTS: Among 8 randomized controlled trials (RCT) including 282 patients met the inclusion criteria, 4 trials were analyzed to compare the ARB with the placebo or no treatment and the other 4 trials were analyzed to compare the ARB with propranolol. Meta-analysis results were as follows. (1)The ARB resulted in more significant hepatic venous pressure gradient (HVPG) reduction as compared with the placebo or no treatment [WMD = 1.87 mm Hg (1 mm Hg = 0.133 kPa), 95%CI (0.86 - 2.87) mm Hg, P = 0.00003]. And the ARB were similar to propranolol in reducing HVPG [WMD = 0.92 mm Hg, 95%CI (-0.41 - 2.26) mm Hg, P = 0.17]. (2)The ARB led to more significant reduction in mean arterial pressure than the placebo or no treatment [WMD = 8.89 mm Hg, 95%CI (7.16 - 10.62) mm Hg, P < 0.000 01], but they were similar to propranolol in giving rise to mean arterial pressure reduction (WMD = 0.41, 95%CI -4.46 - 5.28, P = 0.87) which had no significant difference. And the ARB had no significant effect on the heart rate of the patients, which was similar to no treatment group (P > 0.05). Whereas, propranolol could greatly decrease heart rate of the patients (WMD = -21.25, 95%CI -25.83 - 16.68, P < 0.000 01). (3) No significant differences were found in serum bilirubin and creatinine levels between the ARB and the placebo or no treatment groups (P > 0.05). The rate of nonspecific adverse events was higher in the ARB groups than in the placebo or no treatment groups (P = 0.03), but it showed there was no difference between the ARB and propranolol groups (P = 0.72). CONCLUSION: The ARB is effective in reducing portal hypertension in patients with cirrhosis, which is similar to propranolol. Their effects on mean arterial pressure is similar to propranolol without significant effects on hear rate, liver function and kidney function, and with less nonspecific adverse events. The ARB could become a new choice for the treatment of portal hypertension.

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.

[Identification of Taenia solium with abnormal number of scolex hooklets].

OBJECTIVE: To identify 3 suspected adults Taenia solium with abnormal number of hooklets on scolex collected from 3 patients of Dali in Yunnan Province. METHODS: Tapeworms were observed with unaided eyes. Morphology of the scolices and gravid proglottids was observed under microscope. DNA of gravid proglottids of the 3 adult tapeworms was extracted. T. solium mitochondrial cytochrome c oxidase subunit 1 gene (cox1) fragment and the full coxz1 gene were amplified by PCR. The cox1 gene of one isolate was sequenced. Eggs were hatched and oncospheres were inoculated into mice subcutaneously. Each mouse was subcutaneously injected with 1 mg dexamethasone once daily. Sixty days after infection, all mice were sacrificed and the morphology of cysticerci was observed. Two macaque monkeys were fed with eggs (2.5 x 10(5) per monkey). Euthanasia and autopsy were performed on day 47. Morphology of cysticerci were observed by light and scanning electron microscopy, and pathological changes of livers were observed. RESULTS: The number of hooklets on scolices of the three tapeworms was 0, 4 and 10, respectively, and lateral uterine branches in gravid proglottids were 7-12. PCR results of co1l gene fragment with species-specific primer for T. solium were all positive. The complete sequence of cox1 gene had 99.8% identity to the reported T. solium sequences. Cysticerci were obtained from hypoderm of mouse, muscles and hearts of monkey. Four suckers and 26-28 hooklets ranged in two rows around rostellum on scolex were microscopically observed. Milia-like lesions were found in monkey liver. Histological examination showed that there was fibrous connective tissue hyperplasia and eosinophil infiltration around lesion, and parasites were found in some cysts. CONCLUSION: The three tapeworms with abnormal number of hooklets have all been identified as T. solium. The larvae can infect macaque and lead to muscle and liver cysticercosis.

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.