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Background:. Colorectal cancer (CRC) is the fourth cause of cancer death in China. We aimed to provide national and subnational estimates and changes of CRC premature mortality burden during 2005–2020. Methods:. Data from multi-source on the basis of the national surveillance mortality system were used to estimate mortality and years of life lost (YLL) of CRC in the Chinese population during 2005–2020. Estimates were generated and compared for 31 provincial-level administrative divisions in China. Results:. Estimated CRC deaths increased from 111.41 thousand in 2005 to 178.02 thousand in 2020; age-standardized mortality rate decreased from 10.01 per 100,000 in 2005 to 9.68 per 100,000 in 2020. Substantial reduction in CRC premature mortality burden, as measured by age-standardized YLL rate, was observed with a reduction of 10.20% nationwide. Marked differences were observed in the geographical patterns of provincial units, and they appeared to be obvious in areas with higher economic development. Population aging was the dominant driver which contributed to the increase in CRC deaths, followed by population growth and age-specific mortality change. Conclusions:. Substantial discrepancies were observed in the premature mortality burden of CRC across China. Targeted considerations were needed to promote a healthy lifestyle, expand cost-effective CRC early screening and diagnosis, and improve medical treatment to reduce CRC mortality among high-risk populations and regions with inadequate healthcare resources.

Aims: Catheter ablation of paroxysmal atrial fibrillation (PAF) has been shown to be effective and safe. However, recurrence of PAF varies between 10 and 30% for radiofrequency ablation. There have been no reports comparing long-term recurrence rates following radiofrequency ablation, cryoablation, and three-dimensional guided cryoablation plus radiofrequency ablation. The aim of this study was to observe the long-term recurrence rate of PAF when treated by these three catheter ablation methods, and to explore clinical factors that can potentially predict PAF recurrence following catheter ablation.Methods: There were 238 patients involved in this study, including 106 radiofrequency (RF) ablation cases (RF group), 66 cryoablation cases (Freeze group), and 66 cases treated by three-dimensional guided cryoablation combined with radiofrequency ablation (Freeze-plus-RF group). All patients underwent standardized follow-up. The recurrence rate of atrial fibrillation (AF) in the three groups was calculated. Predictive factors for the recurrence of AF were also investigated.Results: At 48 months (the median follow-up period), the sinus rhythm maintenance rate was 77.4% in the RF group, 72.7% in the Freeze group, and 81.8% in the Freeze-plus-RF group. The maintenance rate of sinus rhythm was highest in the Freeze-plus-RF group, but differences among the three groups were not statistically significant. Further analysis found that the preoperative left atrial appendage emptying velocity (LAAEV) (recurrence vs. no recurrence, 56.58 ± 18.37 vs. 65.59 ± 18.83, respectively, p = 0.003), left atrial (LA) anteroposterior dimension (recurrence vs. no recurrence, 36.56 ± 4.65 vs. 35.00 ± 4.37, respectively; p = 0.028), and LA vertical dimension (recurrence vs. no recurrence, 56.31 ± 6.96 vs. 53.72 ± 6.52, respectively; p = 0.035) were related to postoperative recurrence. Multiple Cox regression analysis showed that only LAAEV was predictive of postoperative recurrence of PAF (hazard ratio: 0.979; 95% confidence interval: 0.961–0.997).Conclusion: Our study found that there was no statistically significant difference in long-term recurrence rates among the RF, Freeze, and Freeze-plus-RF groups. Preoperative LAAEV is an independent predictor of postoperative recurrence of PAF.

Purpose Adult-onset immunodeficiency with anti-interferon (IFN)-γ autoantibodies (anti-IFN-γ Abs) is an immunodeficiency syndrome. Immune dysfunction in this distinct disorder remains to be clarified. Methods We prospectively collected blood samples of 20 patients with anti-IFN-γ Abs and 65 healthy normal subjects. Percentages of lymphocyte subpopulations, most relevant to T-, B-, and NK-cells, and percentages of stimulated lymphocytes with cytokine production were assessed using eight-color flow cytometry. The results were adjusted to age and absolute lymphocyte counts.Results Most (85%) patients presented non-tuberculous mycobacterial infection. Skin lesions were predominantly manifested by neutrophilic dermatoses. Involved lymph nodes had granulomatous inflammation, except 22.2% showing atypical lymphoid hyperplasia without granuloma formation. In the multiple linear regression model, CD4+ T cells and non-activated subpopulations (recent thymic emigrants and naïve subtypes) were significantly decreased with increased expression of activation markers and polarization to Th1, Th17, and Treg. The percentage of NK cells was increased, but two major NK subpopulations, CD56bright and CD56+CD16+ subsets were decreased. Furthermore, NK cells diminished expression of NKp30 and NKp46 with increased CD57 expression. The cytokine production was significantly lower, namely TNF-α in CD4+ T cells (P = 0.009), CD8+ T cells (P < 0.001), and NK cells (P = 0.002); IFN-γ in CD8+ T cells (P = 0.002) and NK cells (P = 0.001); and IL-2 in CD4+ (P < 0.001), and CD8+ (P = 0.005) T cells. Conclusion We conclude that the immune system in patients with anti–IFN-γ Abs could be exhausted which may contribute to the distinct clinicopathologic features.

Background: A single procedure combining left atrial appendage closure (LAAC) plus catheter ablation (CA) has been proven to be safe and feasible for treating atrial fibrillation (AF). However, the influence of treatment modality on left atrial (LA) function is not thoroughly explained.Objective: We aimed to investigate the changes of LA function in persistent AF patients undergoing concomitant LAAC and CA.Methods: The study population comprised 65 patients who underwent combined AF ablation and Watchman LAAC (combined therapy group) in our center, and 65 participants of the AF simple ablation group who were matched based on sex, age, CHA2DS2-VASc score and HAS-BLED score using propensity score matching. During the 1-year follow-up period, two-dimensional echocardiography and speckle tracking echocardiography were performed to assess LA reservoir, conduit, and contractile function.Results: The combined therapy was associated with a significant improvement in the LA reservoir function with increased expansion index and strain indices, including strain and strain rate (SR) during ventricular systole. Conduit function with SR during early ventricular diastole was also improved, as was contractile function with active atrial emptying fraction and SR during atrial systole. Similarly, LA reservoir and contractile function indices all improved continuously during follow-up after catheter ablation alone. At 3 months follow-up LA reservoir and conduit function with strain indices had a tendency to improve only in the simple procedure group. At 1-year follow-up there was no significant difference in either LA volumes or strain indices between the two groups.Conclusion: Both the combined therapy group and the simple ablation group demonstrated significant improvement in LA function. Based upon the fact that LA function was improved in both groups it might be concluded that most of the effects appeared to result from ablation, not LAAC; furthermore the additional LAAC procedure did not affect the improvement of LA function after CA.

CUL4A regulate the termination of autophagy in a physical process. However, the relationship between CUL4A and autophagy in cancer is unclear. We retrospectively investigated 99 intrahepatic cholangiocarcinoma (iCCA) cases. Whole sections were used for immunohistochemical analysis for p62, and LC3B expression. Q-score was defined as the sum of the labeling intensity and proportion. The cut-off point for immunoreactivity was set. CUL4A was overexpressed in cell lines and autophagy reflux was compared after manipulation. The iCCA cases with CUL4A overexpression had significantly higher prevalence of intact activated autophagy (42.4 vs. 15.2%; p = 0.003), which was significantly associated with advance tumor stage (34.1% vs. 15.4%; p = 0.032), less extensive necrosis (8.3 vs. 49.3%; p < 0.001), and shortened disease-free survival (mean, 19.6 vs. 65.5 months, p = 0.015). In vitro, iCCA cells with CUL4A overexpression significantly increased LC3II level as compared to the cells under basal condition. Although both cell types showed intact autophagy with increased LC3II expression after bafilomycin A1 treatment, the accumulation of LC3II was higher in CUL4A-overexpressing cells. CUL4A overexpression increased the proliferation of cells as compared with control cells. After treatment with bafilomycin A1, proliferation was inhibited in both cell types, but the effects were more prominent in the cells overexpressing CUL4A. CUL4A promotes autophagy, and exhibits significantly higher autophagic flux which affects the proliferation of iCCA cells; these effects correlated with advance tumor stage and poor prognosis. Thus, targeting autophagy may be potentially therapeutic in iCCA.

Since early diagnosis of sepsis may assist clinicians in initiating timely, effective, and prognosis-improving antibiotic therapy, we developed an integrated microfluidic chip (IMC) for rapid isolation of both Gram-positive and Gram-negative bacteria from blood. The device comprised a membrane-based filtration module (90 min operating time), a bacteria-capturing module using a micro-mixer containing magnetic beads coated with "flexible neck" regions of mannose-binding lectin proteins for bacteria capture (20 min), and a miniature polymerase chain reaction (PCR) module for bacteria identification (90 min via TaqMan® probe technology). The filter separated all white blood cells and 99.5% of red blood cells from bacteria, which were captured at rates approaching 85%. The PCR assay's limit of detection was 5 colony-forming units (CFU) per reaction, and the entire process was completed in only 4 h. Since this is far less than that for culture-based approaches, this IMC may serve as a promising device for detection of sepsis.

Objectives Severe hyperkalemia can cause life-threatening arrhythmia, cardiac arrest, or death. This study aimed to investigate the incidence and the associated factors relevant to critical hyperkalemia (≥6 mmol/L) among inpatients, outpatients, and emergency department. Their clinical outcomes were also analyzed. Methods All patients whose high serum potassium values had been reported as critical laboratory values in 2016 were enrolled. Their demographic data, comorbidities, clinical symptoms, biochemical data, and outcomes were reviewed and collected. The Charlson comorbidity score (CCS) and glomerular filtration rate (GFR) were computed to assess the comorbidity burden and renal function. Patients were divided into groups according to different settings, potassium and GFR levels, and their survival. Results Of the 293,830 total serum potassium tests, 1,382 (0.47%) reports were listed as critical laboratory values. The average reply time was 6.3 min. Their mean age was 67.2 years, while the average GFR was 12.2 mL/min/1.73 m2. The overall mortality rate was 34%. Patients in the emergency department had the highest incidence (0.92%), while inpatients had the worst outcome (51% mortality). The leading cause of mortality was septic shock. The fatal group had higher rates of clinical symptoms, higher potassium values, CCS, and eGFR (all p Conclusions Most of the responses for the reports were obtained within a short period of time. Patients with reported high critical serum potassium values were characterized by high rates of comorbidity, reduced eGFR, and mortality. The incidence, clinical manifestations, and outcomes varied in the different clinical settings.

Background: Catheter ablation for atrial fibrillation (AF) has been gaining popularity; however, the trend of inflammatory response markers in patients treated with different catheter ablation strategies over time and their predictability of AF recurrence remain unknown. Methods: A total of 210 patients with AF were enrolled and grouped according to surgical mode as follows: freeze group, RF group, and freeze3D group. The subjects were tested for related indexes before and after surgery. To determine AF recurrence during follow up, 24-h ambulatory electrocardiography was performed at two, three, six, and 12 months after surgery. Results: The inflammation indexes of the three groups peaked between one and three days after surgery but fell at different time points (P < .05). The recurrence rate of paroxysmal atrial fibrillation (PAF) was positively correlated with the increase in the percentage of white blood cells and neutrophils after surgery (P < .05). Conclusions: The postoperative inflammation indices peaked and fell at different time points after different catheter ablation methods. In addition, the recurrence rate of AF in patients treated with freeze3D is lower.

Objective: The present study was to compare the incidence of septal defect (SD) in patients with atrial fibrillation (AF) who received radiofrequency ablation or cryoablation. Methods: A total of 293 AF patients were performed with radiofrequency ablation and cryoablation. Cardiac ultrasonography was performed to calculate left atrial diameter (LAD), left atrial ejection fraction (LAEF%), strain rate (SR), left ventricular systolic (SRs), left ventricular diastolic (SRe), and left atrial systole (SRa) before surgery, 3 months and 1 year after surgery. The patients were followed up to observe statin and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) medication, AF recurrence, 6-min walk test, stroke, any symptoms caused by arrhythmia, and re-hospitalization. Results: The levels of LAD and SD were higher, while SRe and SRa were lower in the cryoablation group in the comparison with the radiofrequency ablation group after surgery (P

Rapid diagnosis of sepsis assists clinicians to initiate timely antibiotic therapy and therefore reduce mortality of bacterial infections. In this work, we presented an integrated microfluidic system for fast isolation of bacteria for both gram-positive and gram-negative bacteria directly from human whole blood, which will be crucial in the detection of sepsis. First, a deterministic lateral displacement (DLD) device was used for sample pretreatment of whole blood, which performed continuous separation of leukocytes, erythrocytes and bacteria. With this approach, most of the blood cells were removed while bacteria and platelets were collected. Then the isolated bacteria were captured with magnetic beads surface-coated with flexible neck regions of mannose-binding lectin (FcMBL) using a new 3D micromixer. The entire process including sample pretreatment and bacteria isolation could be completed on an integrated microfluidic system within 2 hours, which is significantly less than the one for the traditional method (i.e. 3 days). This is the first time that an integrated microfluidic system capable of detecting bacteria by using FcMBL was reported, which may provide a promising way to diagnose sepsis.

Low-level cadmium exposure has adverse effects on chronic kidney disease (CKD); however, the risk factors for elevated blood cadmium levels (BCLs) have not been studied in CKD. We conducted a cross-sectional investigation in 200 CKD patients and stratified them by the tertiles of BCL to compare their demographic, environmental, and biochemical data. The factors associated with BCL were identified, and their effects were examined in subgroups. In the analyses, female sex, smoking, and CKD stage 5D were associated with high BCL, and statin was inversely correlated with BCL (odds ratio [95% confidence interval, CI], 6.858 [2.381–19.746], p < 0.001, 11.719 [2.843–48.296], p = 0.001, 30.333 [2.252–408.520], p = 0.010, and 0.326 [0.122–0.873], p = 0.026; deviations of BCL [nmol/L, 95% CI], 2.66 [1.33–4.00], p < 0.001, 3.68 [1.81–5.56], p < 0.001, 3.38 [0.95–5.82], p = 0.007, and −2.07 [−3.35–−0.78], p = 0.002). These factors were also independently correlated with BCL in subgroups, including non-dialysis CKD, hypertensive patients, non-smokers, and male patients. In conclusion, female sex, smoking, and CKD stage 5D were the major risk factors for elevated BCL; additionally, statins were negatively associated with BCL in CKD.

Atrial fibrillation (AF) is a commonly encountered heart arrhythmia and a risk factor for cardiovascular system. The purpose of the present study was to explore the role of long non-coding RNA myocardial infarction-associated transcript (MIAT) in AF and AF-induced myocardial fibrosis and the possible mechanisms involved in this process. We successfully induced an AF rat model. Expression of MIAT presented a dramatic increase, while microRNA (miR)-133a-3p presented a dramatic decrease in atrium tissues of rats with AF induction. In addition, we also found that MIAT was highly expressed and miR-133a-3p was significantly reduced in peripheral blood leukocyte of AF patients. For biological function exploration of MIAT/miR-133a-3p axis, MIAT was knocked down using small hairpin RNA (shRNA) lentivirus injection and the rescue experiments were performed simultaneously by inhibiting miR-133a-3p using anti-miR-133a-3p lentivirus injection in rats with AF. MIAT downregulation significantly alleviated AF, increased atrial effective refractory period (AERP), and reduced the duration of AF as well as cardiomyocytes apoptosis. Whereas these effects of MIAT downregulation on AF were reversed by anti-miR-133a-3p administration. Luciferase reporter revealed that miR-133a-3p was directly regulated by MIAT. Moreover, MIAT knockdown effectively reduced AF-induced atrial fibrosis by detecting reduced collagen in the right atria and inhibited expression of fibrosis-related gene expression of collagen I, collagen III, connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGF-β1) in rats with AF, these findings were in contrast with the findings for rats with inhibition of miR-133a-3p. In conclusion, our study demonstrated the role of MIAT downregulation in alleviating AF and AF-induced myocardial fibrosis, and the functional regulatory pathway of MIAT targeting miR-133a-3p.

Fungal keratitis (FK) is one of the most severe corneal infectious diseases. FK often leads to poor visual prognosis and thus requires accurate diagnosis. Conventional approaches, including clinical diagnoses, smears, and cultures, often fail to provide reliable diagnostic value. Omics approaches, such as those using genomic, metagenomic, and tear proteomic data sources, provide promising features for improving the diagnosis and monitoring the progression of FK. Genomic approaches are based mainly on detecting amplicons of ribosomal RNA genes, and internal transcribed spacers are gradually gaining popularity in clinical practices. A metagenomic approach based on 16S rRNA genes may help monitor the dynamic change of conjunctival microbiota associated with an FK event, whereas that based on shot-gun and 18S rRNA target enrichment sequencing could have the potential to diagnose FK using clinical samples. A tear proteomic approach may provide comprehensive information about ocular surface defense and injury during FK. Representative up- and down-regulated proteins during FK could also be used as biomarkers to determine the clinical course and develop a treatment strategy in different stages of FK. Consequently, a personalized tear proteomic approach will soon play a key role in FK management.

Restoration of sinus rhythm in atrial fibrillation (AF) by radiofrequency catheter ablation (RFCA) is associated with a transient stunning of left atrial (LA) function. However, the long-term effects of different ablation strategies on LA function remain undetermined. We performed randomized controlled trial to evaluate the effects of RFCA, cryoablation, and 3D mapping-guided cryoablation on LA function of proximal AF patients within 1 year. The 3D mapping-guided cryoablation was defined as a maximum of two cryoablation procedures for each pulmonary vein accompanied by RFCA for additional points until complete pulmonary vein isolation was achieved. Conventional and speckle tracking echocardiographic analyses were performed to evaluate LA function. Among the 210 patients (70 in each group) included, a trend of decreasing LA systolic and diastolic function was observed in all groups, as evidenced by decreases in peak A-wave velocity, the global LA peak systolic strain, the peak strain rate, the peak early diastolic strain rate, and the peak late diastolic strain rate within 7 days to 3 months after ablation followed by gradual recovery thereafter. However, the temporal changes in the above four strain parameters among the three groups did not differ significantly within 1 year after ablation (all p > 0.05). Parameters of the LA emptying fraction and LA dimensions were not significantly affected. These results suggested that stunning of LA function occurred within 7 days to 3 months after ablation, and different strategies of AF ablation did not differentially affect the temporal changes in LA function up to 1 year after ablation.

Campylobacter spp. may cause fever, vomiting, and diarrhea in humans. Antibiotic treatment is suggested for patients with severe campylobacteriosis. However, the interpretative criteria for antibiotic susceptibility are inconsistent between Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing guidelines. The aim of the study is to investigate the antibiotic susceptibility and prevalence of cytolethal distending toxin genes and to evaluate antibiotic susceptibility testing methods in the clinical laboratories of two tertiary medical centers in Taiwan. In total, 236 bacterial isolates were collected between 2001 and 2014. The disk diffusion and E-test methods were used to evaluate the antibiotic susceptibility, and broth dilution results were used as a reference. The virulence genes cdtA, cdtB, cdtC, and ceuE were detected through polymerase chain reaction. The antimicrobial sensitivity rates for erythromycin, ciprofloxacin, and tetracycline using the broth dilution assay were 80.4, 5.4, and 3.4%, respectively. No significant differences were observed in the antibiotic susceptibility of the isolates obtained from southern and northern Taiwan. However, some differences were observed between species. The susceptibility test for erythromycin (disk diffusion) showed that the isolates with small inhibition zone diameters were all resistant, and five isolates (4.0%) with large IZDs were non-sensitive. The error rate of the disk diffusion method according to the CLSI M45-A3 guideline was 5.4% (8/148). The incompatibility rates between the E-test and broth dilution methods for erythromycin, ciprofloxacin, and tetracycline were 8.0, 5.3, and 1.3%, respectively. The positive rates of the genes cdtA and cdtC were considerably higher in Campylobacter jejuni than in C. coli. Erythromycin is recommended as the first choice of treatment for campylobacteriosis. The disk diffusion method is suitable for prescreening Campylobacter susceptibility by using the CLSI M45-A2 and EUCAST criteria (low error rate of 3.4%). If antibiotic treatment fails or IZDs are between 6 and 20 mm, minimum inhibitory concentration testing by using the E-test method is highly recommended because the results of the E-test and broth dilution methods exhibit high agreement. The error rate of disk diffusion method using CLSI M45-A3 criteria is only slightly higher than B, which is also a suitable criteria.

Background Neurofibromatosis type 1 (NF1) is one of the most common hereditary neurocutaneous disorders. The malignant peripheral nerve sheath tumor (MPNST), transformed from NF1 related plexiform neurofibroma, is a rapidly growing and highly invasive tumor. No effective chemotherapeutic agent is currently available. Calebin-A is a derivative from turmeric Curcuma longa. Given the anti-inflammatory and anticancer potentials of curcumin, whether Calebin-A also had the tumoricidal effect upon MPNST cells is still elusive. Purpose To determine whether Calebin-A has the potential for anti-MPNST effect. Methods The MTT and FACS analysis of normal Schwann (HSC) and MPNST cells have been employed to determine the tumoricidal effect of Calebin-A. The expression of the signal pathway molecules was assessed by Western blotting. The CHIP with quantitative PCR assay was performed to quantify the promoter DNA binding to acetylated histone 3 (acetyl H3). The enzyme activities of histone acetyltransferase (HAT) and deacetylase (HDAC) have been evaluated by commercial kits. The measurements of tumor size of the xenograft mouse model were also performed. Results Calebin-A inhibited the proliferation of MPNST and primary neurofibroma cells in a dose-dependent manner. The flow cytometry analysis of the MPNST cells after treatment of 25 μm of Calebin-A demonstrated an increase of population in the G0/G1 phase but decrease in G2/M phase. Before treatment, the expression of Axl, Tyro3, and acetyl H3 was significantly higher in MPNST cells when compared to HSC. The expression of phosphorylated-AKT, -ERK1/2, survivin, hTERT, and acetyl H3 proteins were reduced after treatment. The CHIP assay shows the promoter DNA copies of survivin (BRIC5) and hTERT genes are significantly reduced post-treatment. The enzyme activity of HAT was significantly reduced, but not that of HDAC. Two HAT inhibitors, epigallocatechin-3-gallate (EGCG) and anacardic acid (AA) have also demonstrated a significant inhibitory effect on MPNST cells. Finally, the measurements of tumor size showed a significant reduction of the xenograft tumors after treatment of Calebin-A. Conclusion Both in vitro and in vivo studies showed Calebin-A could inhibit the proliferation of MPNST with suppression of survivin and hTERT. The reduced expression of these two factors might be through the epigenetic histone modification resulting from the decreased activity of HAT.

Extranodal nasal-type natural killer (NK)/T-cell lymphoma (NKTCL) is an aggressive lymphoma that is prevalent among East Asian and South American populations. Although Epstein-Barr virus (EBV) is commonly detected in NKTCL, there are limited studies that have analyzed the EBV genomic variations in NKTCL. In this study, 8 EBV latent genes were analyzed using targeted gene sequencing in 23 formalin-fixed paraffin-embedded tissues derived from 18 patients with NKTCL. Five cases with paired samples were comparatively analyzed. The consistency of EBV sequencing data between tissue samples was high (96.3%–98.7%), whereas that of variant calling among the tissue samples and plasma samples (74.3%–79.2%) was low. The highest densities of non-synonymous variants were detected in the EBNA3B gene. Among the 74 known T-cell epitopes, 363 non-synonymous variants were identified in 32 (43.2%) epitopes. Additionally, the AVFDRKSDAK (A1S/P and V2F/M/L) and YHLIVDTDSL (I4L and L10R/V/G/H) epitopes were associated with 5 patterns of amino acid changes in EBNA3B and EBNA-2, respectively. The frequency of variation in the human leukocyte antigen (HLA)-restricted epitopes with corresponding HLA types common among Taiwanese population was significantly low (P = 0.011), whereas that in anchor residues was significantly high (P = 0.012). In conclusion, this study demonstrated the genomic diversity of EBV in NKTCL and its correlation with the HLA-restricted epitope variations in Taiwanese population. The findings of this study provide useful insights for the development of novel therapeutic strategies for NKTCL.

Genome-wide association studies (GWAS) have identified Aldehyde dehydrogenase 2 (ALDH2) as a susceptibility locus for coronary artery disease (CAD) previously. However, the impacts of common variants in this gene on CAD and its outcomes have not been extensively studied. This study explored the association between the Tagging SNPs in ALDH2 and CAD as well as its main outcomes. Six common variants in ALDH2 were selected as tagging SNPs and two cohorts containing 7296 individuals were genotyped to investigate the impacts of ALDH2 on CAD and its main outcomes. The results show that the variant rs671 in ALDH2 is associated with an increased risk of CAD in southern Chinese (OR=1.26, 95%CI: 1.07-1.48, p=0.004), while not in northern Chinese (OR=1.00, 95%CI: 0.86-1.50, p=0.94). Meanwhile, we find that rs671 genotypes may not influence the outcomes of CAD (HR=1.11, 95%CI: 0.892-1.38, p=0.346). Additionally, we also tested the effect of rs671 genotype on CAD severity, while no significant association was found between them. In the subgroup analysis, the results revealed that rs671 were significantly associated with CAD (OR=1.24, 95%CI: 1.11-1.38, p

Objective To investigate myocardial apoptosis and the expression of apoptosis-related proteins [B-cell lymphoma-2 (Bcl-2) and Bax], cardiac hypertrophy, and function in spontaneously hypertensive rats (SHR) during aging. Methods Male SHR (n = 36) and Wistar-Kyoto rats (WKY, n = 30) were monitored for their cardiac function from 14 to 102 weeks of age using echocardiography. Myocardial apoptosis in the subendocardium and subepicardium was analyzed using TUNEL staining. The apoptosis-related proteins (Bcl-2 and Bax) were assessed by Western blot analysis. Results Left ventricular mass index (LVMI) in SHR increased progressively with age. Left ventricular ejection fraction (LVEF) showed no significant difference from 14 to 66 weeks of age, but decreased significantly in SHR from 84 to 102 weeks of age. The apoptotic index (APOI) of myocardial cells in SHR increased with age, in which subendocardial APOI (APOI-endo) increased at 66 weeks and was significantly higher than the age-matched WKY (9.83 ± 3.97 vs. 4.03 ± 2.06, P < 0.05). Additionally, the subepicardial APOI (APOI-epi) increased significantly at 84 weeks of age (P < 0.05). Bax/Bcl-2 ratio was higher in SHR than WKY at 66 weeks (3.98 ± 0.80 vs. 0.29 ± 0.06, P < 0.05), and enhanced further at 102 weeks of age (10.54 ± 1.60 vs. 0.70 ± 0.13, P < 0.05). Myocardial APOI was positively correlated with LVMI (r = 0.83, P < 0.01), negatively with LVEF in 66–102 weeks (r = −0.81, P < 0.01), and positively with Bax/Bcl-2 ratio (r = 0.79, P < 0.01). Conclusion Myocardial apoptosis increases with aging and is associated with progressive left ventricular remodeling and cardiac dysfunction in SHR.

We sought to investigate the association of single nucleotide polymorphisms (SNPs) of the genes involved in βAR signaling with the response of patients to βAR blockers. A total of 2403 hospitalized patients with chronic heart failure (HF) were enrolled in a multicenter observational study as the first cohort and followed up for a mean period of 20 months. Genes for β1AR, β2AR, and the major cardiac G-protein-coupled receptor kinases (GRKs) GRK2 and GRK5 were analyzed to identify SNPs, and patients were stratified according to genotypes. A second independent cohort enrolling 919 patients with chronic HF was applied to validate the observed associations. The signaling properties of the key identified SNPs were assessed in vitro. Our data showed that HF patients harboring the Gly16 allele in the gene for β2AR (ADRB2) had an increased risk of the composite end point relative to patients who were homozygous for Arg16. Notably, these patients showed a beneficial response to βAR-blocker treatment in a G allele-dose-dependent manner, whereas Arg16 homozygotes had no response to βAR-blocker therapy. This Arg16Gly genotype-dependent heterogeneity in clinical outcomes of HF was successfully validated in the second independent population. Besides, the in vitro experiments revealed that G allele carriers were defective in β2AR-coupled inhibitory adenylate cyclase g (Gi) protein signaling.

The World Health Organization, in a 2016 revision, introduced recurrent genetic abnormalities for classifying mature T- and NK-cell neoplasms. However, the role of genetic analyses from lymph node aspiration cytology is still not elucidated. We hypothesize that the use of genetic analyses may increase the accuracy of diagnosis from cytological preparations.Fifty-seven formalin-fixed paraffin-embedded (FFPE) samples were collected for next-generation sequencing (NGS) targeting potential driver mutations including TET2, DMN3TA, IDH2, RHOA, STAT3, and STAT5B. Competitive allele-specific TaqMan polymerase chain reaction (cast-PCR) was performed to validate the mutation status by using FFPE and preoperative fine needle aspiration cytology (FNAC) samples.Among these six candidate genes, only IDH2 and RHOA mutations were significantly more frequent in nodal subtypes, angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) (P = .002 and0.001, respectively). All genes exhibited different mutation patterns except RHOA with a hotspot mutation involving the Gly17 residue. The RHOA G17V mutation was found in 15 (75%) of 20 AITL and two (22%) of nine PTCL, NOS. Cast-PCR using FFPE samples showed 100% concordance with NGS. Among 12 lymph node aspirates, the preliminary diagnoses were suspicious for lymphoma (3, 25%), atypical lymphoid cells (3, 25%) and benign/negative (6, 50%). Cast-PCR detected the RHOA G17V mutation in six (75%) of eight RHOA-mutated aspirates and revealed negative results in all (100%) of four wild-type aspirates, with an 83.3% (10/12) concordance comparing to FFPE samples.The RHOA G17V mutation serves as a useful biomarker for cytological assessment in AITL. The use of cast-PCR is valuable in the diagnosis of malignant lymphomas from cytological preparations, and thus avoiding the potential risks of invasive procedures.

Limited data are available about the role of common variants at the aldehyde dehydrogenase 2 gene (ALDH2) on the clinical outcome in Chinese patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI). In the present study, a total of 1089 patients were consecutively enrolled from January 2012 and July 2013. Six common variants at ALDH2 gene, including rs2339840, rs4648328, rs4767939, rs11066028, rs16941669, and rs671, were selected to test the associations of those polymorphisms with the cardiovascular outcome in patients with CHD after PCI. The clinical endpoints included cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The composite of clinical endpoints was defined as the primary endpoint, and every endpoint alone was considered as the secondary endpoints. The median follow-up time was 38.27 months. Our results showed that the common variant rs2339840 was independently associated with a lower risk of stroke in patients with CHD after PCI (codominant model, HR = 0.32, 95% CI, 0.11–0.91, P = .074 for heterozygotes; HR = 0.25, 95% CI, 0.06–1.14, P = .033 for homozygotes; dominant model, HR = 0.32, 95% CI, 0.14–0.74, P = .007). However, no significant associations were found between other 5 single nucleotide polymorphisms (SNPs) and the clinical endpoints. For the first time, the common variant rs2339840 was reported to be a protective factor against stroke in CHD patients with PCI.

Peripheral mature T and NK cell lymphomas consist of a heterogeneous group of neoplasms with cytogenetic and molecular diversities. TP53 mutation is involved in the events of tumorigenesis and present in a variety of cancer subtypes. However, TP53 mutation in peripheral mature T and NK cell lymphomas has not been extensively investigated. In this study, 57 formalin-fixed paraffin-embedded samples were collected for whole-exome sequencing and immunohistochemical study. Ten cases had TP53 mutation variant allele frequency (VAF) of more than 5%, predominantly in intestinal T-cell lymphoma (60%), peripheral T-cell lymphoma, not otherwise specified (22.2%), and extranodal nasal-type NK/T-cell lymphoma (21.7%). Six of 16 (37.5%) cases with 72Pro homozygous genotype showed higher frequency of TP53 mutation VAF > 5% than did those with 72Arg homozygous genotype (P = .044). To a variable extent, overexpression of p53 was observed in 11 of 56 (19.6%) tumors. The percentage of tumor cells with strong p53 staining was positively correlated with TP53 mutation VAF (R2 = 0.95, P < .001). TP53 mutation and p53 expression tended to indicate poor prognosis (P = .054 and P = .009, respectively). In conclusion, we demonstrated TP53 mutation and p53 expression in subtypes of peripheral mature T and NK cell lymphomas and found positive correlation of this immunostaing pattern with the status of TP53 mutation.

Acute leukemia is one of the commonly diagnosed neoplasms and causes human death. However, the treatment for acute leukemia is not yet satisfactory. Studies have shown that mushroom-derived polysaccharides display low toxicity and have been used clinically for cancer therapy. Therefore, we set out to evaluate the anti-cancerous efficacy of a water-soluble polysaccharide extract from Inonotus taiwanensis (WSPIS) on human acute monocytic leukemia THP-1 and U937 cell lines in vitro. Under our experimental conditions, WSPIS elicited dose-dependent growth retardation and induced apoptotic cell death. Further analysis showed that WSPIS-induced apoptosis was associated with a mitochondrial apoptotic pathway, such as the disruption of mitochondrial membrane potential (MMP), followed by the activation of caspase-9, caspase-3, and PARP (poly(ADP-ribose) polymerase) cleavage. However, a broad caspase inhibitor, Z-VAD.fmk, could not prevent WSPIS-induced apoptosis. These data imply that mechanism(s) other than caspase might be involved. Thus, the involvement of endonuclease G (endoG), a mediator arbitrating caspase-independent oligonucleosomal DNA fragmentation, was examined. Western blotting demonstrated that WSPIS could elicit nuclear translocation of endoG. MMP disruption after WSPIS treatment was accompanied by intracellular reactive oxygen species (ROS) generation. However, pretreatment with N-acetyl-l-cysteine (NAC) could not attenuate WSPIS-induced apoptosis. In addition, our data also show that WSPIS could inhibit autophagy. Activation of autophagy by rapamycin decreased WSPIS-induced apoptosis and cell death. Taken together, our findings suggest that cell cycle arrest, endonuclease G-mediated apoptosis, and autophagy inhibition contribute to the anti-cancerous effect of WSPIS on human acute monocytic leukemia cells.

Insulin receptor substrate 2 (IRS2) is a candidate driver oncogene frequently amplified in cancer and is positively associated with IRS2 expression. The overexpression of IRS2 has been suggested to promote tumor metastasis. However, its function in intrahepatic cholangiocarcinoma (iCCA) has not been investigated extensively. The present study examined 86 cases of iCCA to analyze IRS2 expression and its correlation with clinicopathological characteristics using immunohistochemical assays. Three stable cell lines overexpressing IRS2 were established. The mobility potential of cells was compared in the basal condition and following manipulation using cell migration and invasion assays. Epithelial-mesenchymal transition (EMT)-associated proteins were assessed by western blotting. IRS2 was overexpressed in 29 iCCA cases (33.7%) and was significantly more frequent in cases with large tumor size (P=0.033), classified as an advanced stage by the American Joint Committee on Cancer (P=0.046). In comparison with the control cells, the three IRS2-overexpressing iCCA cell lines exhibited a statistically significant increase in mobility potential. Expression analysis of EMT markers demonstrated decreased epithelial marker levels and increased mesenchymal marker levels in IRS2-overexpressing cells compared with their corresponding control cells. The results of the present study indicate that IRS2 overexpression is characterized by a large tumor size and advanced tumor stage in iCCA, and that it may increase tumor mobility potential by regulating EMT pathways. Therefore, it is a valuable predictive indicator of metastasis and may provide a novel direction for targeted therapy in iCCA.

Background Platelets play an important role in the pathogenesis of acute coronary syndrome (ACS). Patients with ACS have an increased mean platelet volume (MPV) and immature platelet fraction (IPF) resulting in elevation of thrombotic ability. In this study, we evaluated the diagnostic performance of MPV and IPF in identifying suspected ACS patients at emergency department. Moreover, we investigated the correlation between MPV or IPF with initial troponin I (TnI), one of the current ACS biomarkers. Methods This was a single-center study recruiting suspected ACS patients who had acute chest pain at the emergency department. Whole blood samples were obtained from all participants and MPV and IPF were measured by Sysmex XE-5000 hematology analyzer within 20 min of blood sampling. The diagnostic values of MPV and IPF in identifying ACS were analyzed retrospectively. Result In this study, 63 in 104 suspected ACS patients were diagnosed as ACS (65.3%). MPV and IPF were higher in ACS patients compared to non-ACS patients (MPV: 10.7 ± 0.80 fL vs 10.0 ± 0.64 fL, p

The muscle Ras (MRAS) gene polymorphisms have been reported to be associated with coronary artery disease (CAD) in white Europeans. The aim of this study was to ascertain the role of MRAS gene polymorphisms in conferring susceptibility to CAD, and to explore the effect on severity of CAD in Chinese population. We genotyped 5009 Chinese individuals (2466 CAD cases and 2543 controls) for eight single nucleotide polymorphisms (SNPs) around MRAS and used logistic regression analysis to determine whether they were associated with CAD. The association of the SNP loci on the severity of CAD was analyzed using a logistic and linear regression analysis, respectively. Our results revealed that an intron SNP, rs1199337, tends to be marginally associated with CAD as previously reported in Caucasians (nominal P=0.01, OR 1.10, 95% CI 1.01-1.20). However, this association did not retain statistically significant levels after applying Bonferroni's correction for multiple testing (corrected P=0.08). There was no significant association between other loci and CAD (nominal P>0.05). We did not observe any significant association between the SNPs and severity of CAD (all P values>0.05). From the above results, the MRAS gene loci might have a minor effect in conferring susceptibility to CAD in Chinese population.

Background: The conversion of atrial fibrillation (AF) to sinus rhythm is associated with transient dysfunction of the left atrium (LA). This study aimed to investigate the time course of LA function and inflammation after radiofrequency (RF) ablation for paroxysmal AF. Methods: Fifty-three patients with paroxysmal AF undergoing RF ablation were recruited. White blood cells were counted and high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and D-dimer levels were measured. LA emptying fraction, strain, and strain rate were evaluated before RF ablation and at 1, 2, 3, and 4 weeks and 2 and 3 months after ablation using conventional Doppler echocardiography and two-dimensional speckle-tracking echocardiography. Results: LA emptying fraction sharply decreased at day 7 after ablation and then slowly increased (p

The objective of this study was to study the functional changes of the left atrium after radiofrequency ablation treatment for atrial fibrillation and the therapeutic effect of atorvastatin. Fifty-eight patients undergoing radiofrequency ablation for atrial fibrillation were randomly divided into non-atorvastatin group and atorvastatin group. Patients in the atorvastatin group were treated with atorvastatin 20 mg p.o. per night in addition to the conventional treatment of atrial fibrillation; patients in the non-atorvastatin group received conventional treatment of atrial fibrillation only. Echocardiography was performed before radiofrequency ablation operation and 1 week, 2 weeks, 3 weeks, and 4 weeks after operation. Two-dimensional ultrasound speckle tracking imaging system was used to measure the structural indexes of the left atrium. Results indicated that there was no significant change for indexes representing the structural status of the left atrium within a month after radiofrequency ablation (P > 0.05); however, there were significant changes for indexes representing the functional status of the left atrium. There were also significant changes in indexes reflecting left atrial strain status: the S and SRs of atorvastatin group were higher than those of non-atorvastatin group (P < 0.05). In summary, atorvastatin could improve left atrial function and shorten the duration of atrial stunning after radiofrequency ablation of atrial fibrillation.

Background The identification of new risk factors for coronary artery disease (CAD) is increasingly sought in an effort to tackle this threatening disease. β2-microglobulin (B2M) is reported to associate with peripheral arterial disease and adverse cardiovascular outcomes. However, the association between B2M and cardiovascular disease remains under-researched. This study evaluated the effects of B2M on CAD without renal dysfunction. Methods One thousand seven hundred sixty-two subjects (403 non-CAD subjects and 1,359 CAD subjects) were investigated. Fasting samples were collected to determine B2M level. The Gensini and SYNTAX scores were used to assess the severity of CAD. Results CAD subjects were significantly higher in serum B2M level comparing with non-CAD subjects (1.25 ± 0.46 vs 1.14 ± 0.28 mg/L, p

Spinal cord injury (SCI) often results in motor disability concomitant with limit neuroplasticity; the underlying mechanism, however, is still unclear. This study established spinal cord transection rats model (T10), then performed cDNA microarray analysis and found that vimentin located in astrocytes was increased significantly in scar tissues after transection. To understand the role of vimentin and it's mechanism of regulation, RNA interference and luciferase assay were used. Vimentin knockdown in the scar tissues showed a significant improvement on locomotor function in hindlimbs, while vimentin overexpression exhibited an opposite effect. In vitro, vimentin downregulation or overexpression can effectively inhibit or increase astrogliosis, respectively. Moreover, by using biological informatics technology, we predicted that vimentin may be as the target of micRNA138 (miR-138), and confirmed that miR-138 could regulate vimentin by luciferase activity assay. The present results not only validated the exact role of vimentin in transected spinal cord, but also exhibited a novel regulation mechanism, in which miR-138 may regulate vimentin to promote neuroplasticity. It, therefore, provides a novel target for gene drug discovery based on miRNA-138 or vimentin for the treatment of SCI in the future clinic trial.

Background Gene variants contribute to variability in individual responsiveness to clopidogrel and influence cardiovascular outcomes in Caucasian patients with acute coronary syndrome (ACS). However, limited data is available in Asian populations. Methods We resequenced 14 genes in metabolizing and activity pathway of clopidogrel in 138 patients with ACS and prospectively assessed the modulating effects of 13 variants possibly related to clopidogrel efficacy on one-year cardiovascular event occurrence in 5820 ACS patients after percutaneous coronary intervention (PCI). In addition, platelet aggregation rate was measured in 1084 participants and plasma levels of active metabolite were determined in 15 patients to test whether increasing clopidogrel maintenance doses increases active metabolite exposure. Results No significant associations were found between any of the tested variants and risk of cardiovascular events ( P >0.05), although CYP2C19*2 carriers had slightly higher on-treatment platelet aggregation rate and lower active metabolite exposure compared with that of non-carriers (Median [IQR] 51.49 [35.43–66.75] vs. 49.05 [32.36–63.38], P =0.012) (means±SD AUC, 22.84±5.00 vs. 35.05±12.34, P =0.008). Switching from 75mg daily clopidogrel to 150mg daily fully overcomes low exposure to clopidogrel active metabolite in CYP2C19*2 carriers (means±SD AUC, 32.35±8.65 vs. 35.05±12.34, P =0.314). Conclusion Different from Caucasian populations, genetic variants have no significant influence on clinical outcomes and have much milder effects on inhibition of platelet and active clopidogrel metabolite levels in Chinese patients with ACS after PCI, an effect which could be overcome with a dose escalation to 150mg daily.

Background Patients with arsenic-induced Bowen’s disease (As-BD) are at risk of developing invasive cancers in the skin, lung, and urinary bladder. However, a longitudinal follow-up study on the association between As-BD and invasive cancers is still lacking. Objectives This study aims to investigate the underlying molecular mechanisms of this malignant progression in the skin and internal organs. Methods This is a biopsy-based follow-up study. We tested the DNA histograms, Cyclin D1 (CCND1) protein expression and CCND1 promoter DNA methylation in 40 pathologically confirmed specimens from As-BD patients to correlate with individual’s invasive cancer occurrence in the 5-year follow-up. Results Flow cytometric DNA histogram analysis of skin specimens showed aneuploid (n = 15), G2/M arrest (n = 22), and normal (n = 3) DNA histograms. No patients with normal DNA histograms developed invasive cancers, whereas 13 developed invasive cancers in the aneuploid group and 2 developed invasive cancers in the G2/M arrest group. The aneuploid group showed a high risk of invasive cancer development. In all assessed aneuploid specimens, the CCND1 promoter hypomethylation was observed. Statistically, percentage of un-methylation more than 55.85% among 17 detected CpG sites showed extremely high predictive power in the occurrence of invasive arsenical cancers. Furthermore, the un-methylation at -56 and -54 bp CpG sites was statistically significantly associated with invasive arsenical cancer development (p = 1.29 × 10−5). Conclusions As-BD lesions showing an aneuploid DNA histogram had a high risk of invasive cancer development. Un-methyaltion at -56 and -54 bp CpG in the CCND1 promoter serves as a predictor for invasive progression in As-BD patients.

TSL-1 is a fraction of the aqueous extract from the tender leaf ofToona sinensis Roem, a nutritious vegetable. The pandemic influenza A (H1N1) virus is a recently described, rapidly contagious respiratory pathogen which can cause acute respiratory distress syndrome (ARDS) and poses a major public health threat. In this study, we found that TSL-1 inhibited viral yields on MDCK plaque formation by pandemic influenza A (H1N1) virus on infected A549 cells with high selectivity index. Meanwhile, TSL-1 also suppressed viral genome loads in infected A549 cells, quantified by qRT-PCR. This study further demonstrated that TSL-1 inhibited pandemic influenza A (H1N1) virus activity through preventing attachment of A549 cells but not penetration. TSL-1 inhibited viral attachment through significant downregulation of adhesion molecules and chemokines (VCAM-1, ICAM-1, E-selectin, IL-8, and fractalkine) compared to Amantadine. Our results suggest that TSL-1 may be used as an alternative treatment and prophylaxis against pandemic influenza A (H1N1) virus.

This study is to evaluate the effectiveness of a modified single-armed suture technique for microsurgical vasoepididymostomy (VE) in patients with epididymal obstructive azoospermia. From September 2011 to December 2011, microsurgical two-suture longitudinal intussusception VEs were performed using our modified single-armed suture technique in 17 men with epididymal obstructive azoospermia at our hospital. Two of these patients underwent repeated VEs after previous failed VEs, and one patient underwent unilateral VE because of an occlusion of the left abdominal vas deferens. The presence of sperm in the semen sample at 3 months postoperation was used as the preliminary endpoint of this study. Each patient provided at least one semen sample at the 3-month time point, and the patency was assessed by the reappearance of sperm (10(4) ml(-1)) in the semen. The mean operative time for the modified technique was 219 min. Patency was noted in 10 men (58.8%), including one patient who underwent repeated VE. The patient who underwent unilateral anastomosis manifested no sperm postoperatively in his semen. Sperm granulomas were not detected in this cohort. The results of this study demonstrate that our modified technique for microsurgical longitudinal intussusception VE is effective. We believe that it is a practical alternative that may reduce operation time and obviate the suture crossing.

Combined hepatocellular carcinoma and cholangiocarcinoma (CHC) is a rare liver cancer which shares unequivocal features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). A greater awareness of genetic relationship between HCC and CC components is limited. To help characterize this rare liver neoplasm, we described clinicopathologic features and evaluated copy number (CN) changes in this study. A total of 13 cases of CHC were collected. Four paired HCC and CC components from four cases were first subject to genome-wide analysis. Nine target genes were subsequently selected for further analysis using quantitative polymerase chain reaction. The paired HCC and CC components in each case had a concordant trend of CN gain or loss in these nine genes. However, the magnitude of concordant CN gain or loss was different. There were significant differences of CN copies between HCC and CC in each case. We demonstrate genetic divergence between HCC and CC components in CHC.

Purpose The purpose of this study is to evaluate the performance of gallium-67 scan (GS) and F-18 fluorodeoxyglucose (FDG) PET scan in lymphoma staging and recurrence detection by comparing the 2 imaging studies in the same patient. Materials and methods A total of 42 patients from the period between July 2002 and May 2006 were included in this study. Of the 42 patients, 6 had Hodgkin disease and 36 had non-Hodgkin lymphomas. All of them underwent one or more FDG PET scans and also underwent corresponding GS performed within 7 days of FDG PET, for staging or detection of lymphoma recurrence. Among the non-Hodgkin lymphoma cases, 18 were diffuse large B-cell lymphoma, 10 were follicular center cell lymphoma, and 8 were of other types. Of the total 46 pairs of imaging performed in these 42 patients, 27 were for staging, and 19 for restaging after recurrence. Results In all these studies, FDG PET detected 230 lesion sites, whereas GS detected 85 lesion sites. All of the lesions detected by GS were noted on FDG PET, whereas GS detected only 37.0% of the lesions detected by FDG PET. Among the 27 studies for staging, FDG PET detected 120 lesions, whereas GS detected 68 lesions (56.7%). In the 19 images taken for relapse, FDG PET detected 110 lesions, whereas GS detected only 17 (15.5%). Conclusions FDG PET is superior to GS in staging and detecting all types of lymphoma. The difference is notably more significant in recurrence detection.

This study examined the role of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and cystatin C in ischemic stroke complicating atrial fibrillation (AF) and the relationship of systemic inflammation with this disease in order to identify AF patients who are at high risk of stroke and need optimal anticoagulant therapy. A total of 103 AF patients, simple (n=75) or complicated by ischemic stroke (n=28), and 112 control subjects were recruited. IL-6 level was detected by using enzyme linked immunosorbent assay. Cystatin C and hsCRP levels were measured by means of a particle-enhanced immunonephelometric assay. The results showed that the AF patients had higher levels of hsCRP (P=0.004), IL-6 (P=0.000), and cystatin C (P=0.000) than control subjects. Plasma hsCRP level was increased in the AF patients with ischemic stroke as compared to the patients with simple AF (P=0.036). The AF patients who had the level of hsCRP exceeding 3.83 mg/L were at a higher risk than those with hsCRP level lower than 3.83 mg/L (P=0.030). After adjusting for other factors, cystatin C remained positively associated with IL-6 (r=0.613) and hsCRP (r=0.488). It was concluded that hsCRP is positively correlated with ischemic stroke complicating AF and may be a risk factor independent of other risk factors for AF. Elevated cystatin C level is also indicative of the increased risk of AF.

Summary Objective To better understand the clinical characteristics of soft tissue infections caused by Shewanella in humans. Methods We report a case of Shewanella soft tissue infection and review the English literature from a search of PubMed. Results A total of 27 adults (mean age 61.1±16.0 years) with soft tissue infections caused by Shewanella were included for analysis. Limb involvement was found in 22 (81.5%) patients, while scalp, face, perineum, lacrimal sac, and abdominal wall involvement were each found in one patient. Chronic ulcer over the leg (14 cases (51.9%)), steroid use (four cases (14.8%)), and liver cirrhosis (three cases (11.1%)) were the major underlying conditions. Shewanella bacteremia was found in 14 out of 22 patients with soft tissue infections involving the limbs. Two patients died of septicemia, giving a mortality rate of 7.4%. Conclusions Shewanella soft tissue infections usually develop in immunocompromised patients with a preexisting cutaneous ulcer (particularly over the legs) after marine environment or seawater exposure. In view of the possible catastrophic consequences, education on the prevention of Shewanella soft tissue infections in at-risk people (e.g., the immunocompromised or elderly with a cutaneous ulcer) relating the need to avoid exposure to the marine environment or seawater may be of importance.

Primary pulmonary pleomorphic adenoma is a rare tumor. Although it is a tumor with benign histology, it has potential to recur or metastasize. Most patients with pulmonary pleomorphic adenomas have symptoms and signs of chronic bronchial obstruction. Some are asymptomatic, presenting as an incidental finding on chest X-ray. Treatment of choice is complete surgical removal. We report our experience of FDG-PET in a patient with primary pleomorphic adenoma. The tumor was represented with high FDG uptake with maximal standard uptake value (SUVmax) of 8.4. It could not be differentiated from a malignant lesion by FDG-PET. This patient received surgical removal of the tumor. No recurrent or metastatic disease noted 26 months following the surgery.

Objective To observe the effects of herb therapy for benefiting qi and removing blood stasis on ultrastructure of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) of uterine endometrium in rabbits with copper intrauterine device. Methods Fifty-six rabbits were randomly divided into seven groups, which were normal control group, sham-operation group, untreated group, indomethacin-treated group and low-, medium- and high-dose Gonghuan Zhixueling Recipe (GHZXLR)-treated groups. The rabbits in the last five groups were operated with copper IUD insertion and then orally given distilled water, indomethacin and low-, medium- and high-dose GHZXLR respectively for at least one week. Rabbits in the normal control group and sham-operation group were given distilled water orally. The ultrastructure of VECs and VSMCs of uterine endometrium in rabbits was observed by transmission electron microscopy. Results The morphological changes of VSMCs revealed intracellular edema, organelle disintegration and decrease of organelle amount, or cell atrophy and vacuolar degeneration of mitochondria in the untreated group, and the amount of collagen fibers also increased outside the VSMCs. Local interstitial edema in subendothelial substance and vacuolar degeneration of mitochondria in VECs were both observed. The ultrastructural damages to the mitochondria, Golgi bodies and myofilament of VECs and VSMCs and the intercellular substance in GHZXLR-treated groups were slighter than those in the untreated group, while these damages had no significant differences as compared with those in the indomethacin-treated group. Conclusion The Chinese herb therapy for benefiting qi for removing blood stasis has the protective effect on VECs of uterine endometrium in the rabbits with copper intrauterine device. It appears to be a good treatment for menorrhagia induced by copper IUD insertion.

Background: Genome-wide-association studies have identified the TMPRSS6 polymorphism rs855791 has the strongest association with red blood cell indices or iron parameters in general population. Whether this genetic variant influences the susceptibility of iron deficiency anemia (IDA) in women with menstruation has not been well studied. Methods: In this case-control study, we enrolled 67 women with IDA and 107 healthy volunteers, and analyzed their complete blood counts, rs855791 genotypes, and menstrual amounts. Menstrual blood loss was evaluated with a pictorial blood-loss assessment chart. Results: There were significantly fewer rs855791 C homozygotes in the IDA group than in the healthy group (11.9% vs. 25.2%, p = 0.03). The odds ratio (OR) of C homozygotes having IDA versus non-CC subjects having IDA was 0.4 (95% CI, 0.17 - 0.95, p = 0.04). When the analysis was confined to study subjects with menorrhagia, this difference became more prominent (9.6% vs. 28.6%, p = 0.01; OR, 0.27, 95% CI, 0.09 - 0.77, p = 0.01). For women with non-CC genotypes, there was an inverse correlation between hemoglobin levels and menstrual loss (p < 0.001); however, this association was not found for those with genotypes CC (p = 0.15). Conclusions: Our study suggests homozygosity for TMPRSS6 rs855791 C genotype has a protective role against IDA in women at reproductive age, especially in those with menorrhagia.

Purpose: To evaluate the treatment outcome, patterns of failure, and prognostic factors for patients with unresectable hepatocellular carcinoma (HCC) treated with local radiotherapy alone or as an adjunct to transcatheter arterial chemoembolization (TACE). Methods and Materials: From March 1994 to December 1997, 25 patients with unresectable HCC underwent local radiotherapy to a portion of the liver. Twenty-three patients were classified as having cirrhosis in Child-Pugh class A and 2 in class B. Mean diameter of the treated hepatic tumor was 10.3 cm. Mean dose of radiation was 46.9 ± 5.9 Gy in a daily fraction of 1.8–2 Gy. Sixteen patients were also treated with Lipiodol and chemotherapeutic agents mixed with Ivalon or Gelfoam particles for chemoembolization, either before and/or after radiotherapy. Percutaneous ethanol injection therapy (PEIT) was given to one patient. All patients were monitored for treatment-related toxicity and for survival and patterns of failure. Results: In a median follow-up period of 23 months, 11 patients were alive and 14 dead. The median survival duration from treatment was 19.2 months with a 2-year survival of 41%. Only 3 of 25 patients had local progression of the treated hepatic tumor. The recurrences were seen within the liver or extrahepatic. The 2-year local, regional, and extrahepatic progression-free survival rates were 78%, 46%, and 39%, respectively. The local control ranked the highest. Patients with Okuda Stage I disease had significantly longer survival than those with Stage II and III ( p = 0.02). Patients with T4 disease ( p = 0.02) or treated with radiotherapy alone ( p = 0.003) had significantly shorter survival. T4 disease ( p = 0.03) and pretreatment alpha-fetoprotein level of more than 200 ng/ml ( p = 0.03) were associated with significantly worse regional progression-free survival. A significant difference was observed in both regional progression-free survival ( p = 0.0001) and extrahepatic progression-free survival ( p = 0.005) between patients with and without portal vein thrombosis before treatment. The presence of satellite nodules had a significantly worse impact on regional progression-free survival ( p = 0.04) and extrahepatic progression-free survival ( p = 0.03). Patients with hepatic tumor more than 6 cm in diameter or portal vein thrombosis tended to have shorter survival. Radiation-induced liver disease (RILD) and gastrointestinal bleeding were the most common treatment-related toxicities. Conclusion: Radiotherapy is effective in the treatment of patients with unresectable HCC. Its effect appeared to be more prominent within the site to which radiation was given. The combination of TACE and radiation was associated with better control of HCC than radiation given alone, probably due to the selection of patients with favorable prognosis for the combined treatment. A dose–volume model should be established in the next phase of research in the treatment of unresectable HCC.

BACKGROUND Tuberculosis (TB) has recently re-emerged as a major public health threat worldwide. There is strong evidence that host genetic factors influence individual susceptibility to TB and that, once infected, young children and immunocompromised patients are at increased risk for mycobacterial disease and progression to extrapulmonary lymphadenitis. METHODS The association between polymorphisms of mannose-binding lectin and the susceptibility of 139 children with cervical mycobacterial lymphadenitis and infected with Mycobacterium tuberculosis was investigated. RESULTS The frequencies of genotypes A/B and B/B, based on codon 54 polymorphisms, were significantly different in TB-infected versus healthy control subjects. The frequency of the A/B genotype was significantly lower in TB-infected children (odds ratio = 0.56; 95% confidence interval: 0.36-0.87; P = 0.01), and the B/B genotype was significantly higher in TB-infected children (odds ratio = 4.68; 95% confidence interval: 1.35-16.3; P = 0.01) compared with healthy controls. The HYB haplotype appeared significantly more often to be protective in the healthy control population (odds ratio = 0.23; 95% confidence interval: 0.05-0.96; P = 0.046). Ex vitro phagocytosis assays indicated that high-expression mannose-binding lectin genotypes are associated with an increased risk of infection with M. tuberculosis. CONCLUSIONS The present study suggests that mannose-binding lectin can protect against TB or predispose the host to the disease depending on the haplotype pair of the host. The low-expression genotype A/B and the HYB haplotype may be associated with protection against intracellular mycobacterial infections, whereas the high-expression genotype A/A may confer susceptibility to disease.

Intravenous radionuclide cholescintigraphy (IVRC) provides a very specific picture for choledochal cysts. However, the clinical significance of the non-visualization of the gall-bladder (GB) activity in these cases is unclear. In this study, we reviewed 27 patients with choledochal cysts who underwent IVRC within 7 days prior to operation and correlated the GB findings on IVRC with the histopathological results. In 18 of the 27 patients (66.7%), there was non-visualization of the GB at 4 h post injection. Among these, two had histopathological features of acute cholecystitis (AC), 11 had chronic cholecystitis (CC), and five had normal GBs. In the other nine patients with visualization of the GB, there were five cases of CC and four normal GBs. If we apply the finding of non-visualization of the GB at 4 h post injection as the criterion for the diagnosis of AC, the diagnostic accuracy was only 40.7% (11/27). We concluded that: (1) GB disease (AC and CC) was common (66.7%: 7.4% and 59.3% respectively) in choledochal cyst patients. (2) Non-visualization of the GB on IVRC did not necessarily indicate AC in choledochal cyst cases, and the diagnostic accuracy was low. (3) GB disease is not the only cause of GB non-visualization on IVRC. A huge choledochal cyst causing a mass or reservoir effect may be a cause of GB compression and result in non-visualization of the GB.

In order to investigate hypoglycemic effects of Momordica charantia(MC) leaves saponins, saponins with purity of 86.0% were extracted from leaves of MC. The extracts were used to treat hyperglycemic rats and the damaged insulinoma cell RIN-M5F in vitro. The effects of MC leaves extracts on the metabolic parameters (serum glucose, insulin, glycogen, Superoxide Dismutase(SOD) activity and Malonedialdehyde (MDA) levels of hyperglycemic rats and the effects on RIN-M5F cells were observed. The results showed that there was a significant increase in serum insulin and glycogen, accompanied by a decrease in serum glucose and MDA in treated rats with MC leaves saponins. And the extracts also exhibited obvious protection and repairation effects on RIN-M5F cells.

Bowen's disease (BD), a carcinoma in situ of the skin, has been identified as an early lesion in arsenic carcinogenesis. Patients with arsenic-induced Bowen's disease (As-BD) showed both cutaneous and systemic immune dysfunctions. We set out to evaluate the interactions between keratinocytes and lymphocytes in the context of As-BD carcinogenesis. Our results showed that As-BD lesions demonstrated a significant dermal CD4+ cell, an essential regulator of proper tumor immunity, undergoing apoptosis. In addition, it was found that the As-BD patients have lower percentage of peripheral CD4+ cells as compared with control subjects. However, the CD4+ cells from As-BD patients were less susceptible to arsenic-induced apoptosis, due to reduced tumor necrosis factor receptor 1 expression. Interestingly, arsenic was found to induce Fas expression on CD4+ cells and increase the soluble Fas ligand (sFasL) production from keratinocytes. This sFasL-containing keratinocyte supernatant was able to induce comparable CD4+ cell apoptosis for both patients and controls. Using immunofluorescent staining, increased FasL was observed in keratinocytes of As-BD lesions and Fas was expressed among infiltrating CD4+ cells. Our findings suggested that systemically, the percentage of CD4+ cells was decreased in the peripheral blood of As-BD patients. These residual CD4+ cells were less susceptible to arsenic-induced apoptosis. However, once infiltrated into the As-BD lesions, the selective CD4+ cell apoptosis might be mediated by FasL from keratinocytes. This additional tumor-anti-immune phenomenon present in the cutaneous environment provides a reasonable explanation for frequent occurrence of arsenic cancers in the skin.

Background: Pulmonary cryptococcosis is an uncommon cause of pulmonary nodules found by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans. It is rarely reported but may mislead interpretation. Purpose: To describe the 18F-FDG PET/CT findings of pulmonary cryptococcosis. Material and Methods: The 18F-FDG PET/CT images of seven patients with pulmonary cryptococcosis were evaluated. Results: The 18F-FDG PET/CT exams showed single or multiple nodular lesions. The standardized uptake values (SUV) in early images varied significantly for the seven patients (ranging from 2.2 to 11.6). Delayed SUVs showed significant increases in four patients. Conclusion: Pulmonary cryptococcosis mimics primary or metastatic lung cancer on 18F-FDG PET/CT scan. Tissue confirmation should be considered for any suspicious pulmonary nodules found on 18F-FDG PET/CT scan with an SUV score higher than 2.5, in order to avoid overdiagnosis or overstaging.

Women with non-small cell lung cancer (NSCLC) appear to have better survival. This study aimed to evaluate sex differences in NSCLC in recent years. The true effect of gender on the overall survival was analyzed taking other prognostic factors into account.A cohort of consecutive NSCLC patients was prospectively enrolled from January 2002 to December 2005, and followed-up until December 2006. They were clinically and pathologically staged and underwent homogenous treatment algorithms. Demographics, histology, and disease stage between sexes were compared. The clinical prognostic factors to be analyzed in addition to gender included stage, age, smoking history and histology. The overall survival of females and males within relevant subgroups defined by smoking history and histology was also compared.Of the 738 patients, 695 were analyzed with a definite stage (94.2%; 315 females and 380 males), which was similar in both sexes. Females were younger (median age: 59.5 years vs. 65.0 years; P0.001) and more likely to have adenocarcinoma (81% vs. 60.5%; P0.001). Patients with earlier stage, younger patients, never-smokers and females had better overall survival in univariate analyses and no significant survival difference was noted between adenocarcinoma and squamous cell carcinoma. Multivariate analyses demonstrated age, smoking history and gender to have a hazard ratio 1.46 (95% confidence interval, CI 1.21-1.76; P0.001), 1.27 (95% CI 0.97-1.65; P=0.082), and 1.18 (95% CI 0.90-1.55; P=0.226), respectively. Subgroup analyses revealed the survival of never-smoker males with adenocarcinoma was similar to that of females.There are sex-related differences in the clinico-pathologic characteristics and survival of NSCLC patients. The survival advantages of females could be attributed to the younger age and lower smoking prevalence. Never-smokers with adenocarcinoma should be given special attention regardless of sex as they imply better survival with different treatment outcomes.

Objective and background: Integrated PET and CT (PET/CT) is accurate in detecting hilar-mediastinal metastases. However, it has a moderate positive predictive value, necessitating pathological verification, especially in situations in which the result would make a difference to treatment. This study aimed to evaluate the performance of transbronchial needle aspiration (TBNA) for hilar-mediastinal lesions suspicious on PET/CT. Methodology: A retrospective study was conducted on 19 patients with a total of 25 positive hilar-mediastinal lymph nodes localized on PET/CT. Standard TBNA technique with rapid on-site cytopathology was performed. Results: The mean short-axis diameter of the positive lymph nodes identified on PET/CT was 9.9 ± 3.0 mm. The sensitivity, specificity and diagnostic accuracy of PET/CT-guided TBNA were 81.8%, 100% and 84%, respectively. The number of needle passes to successful lymph node aspiration or a diagnosis of cancer was 2.36 ± 0.49. Nine of the 25 positive lymph nodes (36%) on PET/CT were smaller than 1.0 cm. The accuracy and sensitivity of TBNA for these subcentimetre nodes was 88.9% and 87.5%, respectively. TBNA replaced surgical sampling in 15 patients (78.9%) with positive lymph nodes on PET/CT. In seven non-small cell lung cancer patients, diagnosis and staging were possible in the one procedure. No complications were encountered. Conclusion: PET/CT can identify small malignant lymph nodes that can then be successfully biopsied by TBNA with on-site cytopathology.