Values of D-D, CRP, ESR and Routine Blood Indicators in Perioperative Treatment of Patients with Orthopedic Trauma.

BACKGROUND: We aimed to explore the values of D-dimer (D-D), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and routine blood indicators in the perioperative treatment of patients with orthopedic trauma. METHODS: A total of 170 patients treated from January 2019 to May 2022 were enrolled and assigned into an infection group (n = 71) and a non-infection group (n = 99) according to whether they had infection in the perioperative period. The levels of D-D, CRP, ESR, and routine blood indicators were detected, and their correlations with perioperative infection were analyzed. RESULTS: The levels of D-D, CRP, ESR, procalcitonin, leukocyte and neutrophil indicators in the two groups significantly increased 3 days after surgery compared with those before surgery (p < 0.05), and they were higher in the infection group (p < 0.05). In the infection group, the D-D, CRP, and ESR levels had no significant differences between males and females or between elderly and non-elderly patients 1 and 3 days after surgery (p > 0.05). They were significantly lower in patients with good prognosis than those with poor prognosis, and significantly increased after infection in comparison with those before confirmed infection (p < 0.05). CONCLUSIONS: ESR, CRP, D-D, and routine blood indicators are of important guiding significance in the perioperative period of patients with orthopedic trauma, based on which early infection can be diagnosed.

Development of a xylose-inducible promoter and riboswitch combination system for manipulating gene expression in Fusobacterium nucleatum.

Inducible gene expression systems are important for studying bacterial gene function, yet most exhibit leakage. In this study, we engineered a leakage-free hybrid system for precise gene expression controls in Fusobacterium nucleatum by integrating the xylose-inducible expression system with the theophylline-responsive riboswitch. This innovative method enables concurrent control of target gene expression at both transcription and translation initiation levels. Using luciferase and the indole-producing enzyme tryptophanase (TnaA) as reporters, we demonstrated that the hybrid system displays virtually no observable signal in the absence of inducers. We employed this system to express FtsX, a protein related to fusobacterial cytokinesis, in an ftsX mutant strain, unveiling a dose-dependent manner in FtsX production. Without inducers, cells form long filaments, while increasing FtsX levels by increasing inducer concentrations led to a gradual reduction in cell length until normal morphology was restored. Crucially, this system facilitated essential gene investigation, identifying the signal peptidase lepB gene as vital for F. nucleatum. LepB's essentiality stems from depletion, affecting outer membrane biogenesis and cell division. This novel hybrid system holds the potential for advancing research on essential genes and accurate gene regulation in F. nucleatum. IMPORTANCE Fusobacterium nucleatum, an anaerobic bacterium prevalent in the human oral cavity, is strongly linked to periodontitis and can colonize areas beyond the oral cavity, such as the placenta and gastrointestinal tract, causing adverse pregnancy outcomes and promoting colorectal cancer growth. Given F. nucleatum's clinical significance, research is underway to develop targeted therapies to inhibit its growth or eradicate the bacterium specifically. Essential genes, crucial for bacterial survival, growth, and reproduction, are promising drug targets. A leak-free-inducible gene expression system is needed for studying these genes, enabling conditional gene knockouts and elucidating the importance of those essential genes. Our study identified lepB as the essential gene by first generating a conditional gene mutation in F. nucleatum. Combining a xylose-inducible system with a riboswitch facilitated the analysis of essential genes in F. nucleatum, paving the way for potential drug development targeting this bacterium for various clinical applications.

A near-infrared probe for detecting and interposing amyloid beta oligomerization in early Alzheimer's disease.

BACKGROUND: The misfolding and deposition of amyloid beta (Aß) in human brain is the main hallmark of Alzheimer's disease (AD) pathology. One of the drivers of Alzheimer´s pathogenesis is the production of soluble oligomeric Aß, which could potentially serve as a biomarker of AD. METHODS: Given that the diphenylalanine (FF) at the C-terminus of Aß fragments plays a key role in inducing the AD pathology, based on the hydrophobic structure of FF, we synthesized a near-infrared BF2-dipyrrolmethane fluorescent imaging probe (NB) to detect both soluble and insoluble Aß. RESULTS: We found that NB not only binds Aß, particularly oligomeric Aß, but also interposes self-assembly of Aß through π-π interaction between NB and FF. CONCLUSION: This work holds great promise in the early detection of AD and may also provide an innovative approach to decelerate and even halt AD onset and progression.

Verbascoside protects from LPS-induced septic cardiomyopathy via alleviating cardiac inflammation, oxidative stress and regulating mitochondrial dynamics.

BACKGROUND: Verbascoside (VB), as an active component of multiple medicinal plants, has been proved to exert anti-oxidative, anti-aging and neuroprotective effects. This study was designed to investigate whether VB could play a cardioprotective role in septic heart injury. METHODS: Mice were injected with lipopolysaccharide (LPS; 10 mg/kg) to induce sepsis. The treatment group received an intraperitoneally injection of VB (20 mg/kg) before LPS challenge. Transthoracic echocardiography, ELISA, immunofluorescence, and qPCR were performed to assess the effect of VB on heart function, oxidative stress, inflammation and apoptosis. Transmission electronic microscopy and immunoblotting were used to evaluate the mitochondrial morphology and biogenesis of the septic heart. In vitro experiments were also performed to repeat above-mentioned assays. RESULTS: Compared with LPS group, the VB treatment group showed improved cardiac function in sepsis. VB alleviated oxidative stress and inflammatory cell infiltration, as well as cardiomyocyte apoptosis. Specifically, VB could restore sepsis-induced mitochondrial alterations via regulating mitochondrial biogenesis. These results were also confirmed in in vitro experiments. CONCLUSION: Verbascoside could protected from sepsis-induced cardiomyopathy by inhibiting oxidative stress, inflammation, and apoptosis, as well as promoting mitochondrial biogenesis.

Telomerase therapy reverses vascular senescence and extends lifespan in progeria mice.

AIMS: Hutchinson-Gilford progeria syndrome (HGPS) is an accelerated ageing syndrome associated with premature vascular disease and death due to heart attack and stroke. In HGPS a mutation in lamin A (progerin) alters nuclear morphology and gene expression. Current therapy increases the lifespan of these children only modestly. Thus, greater understanding of the underlying mechanisms of HGPS is required to improve therapy. Endothelial cells (ECs) differentiated from induced pluripotent stem cells (iPSCs) derived from these patients exhibit hallmarks of senescence including replication arrest, increased expression of inflammatory markers, DNA damage, and telomere erosion. We hypothesized that correction of shortened telomeres may reverse these measures of vascular ageing. METHODS AND RESULTS: We generated ECs from iPSCs belonging to children with HGPS and their unaffected parents. Telomerase mRNA (hTERT) was used to treat HGPS ECs. Endothelial morphology and functions were assessed, as well as proteomic and transcriptional profiles with attention to inflammatory markers, DNA damage, and EC identity genes. In a mouse model of HGPS, we assessed the effects of lentiviral transfection of mTERT on measures of senescence, focusing on the EC phenotype in various organs. hTERT treatment of human HGPS ECs improved replicative capacity; restored endothelial functions such as nitric oxide generation, acetylated low-density lipoprotein uptake and angiogenesis; and reduced the elaboration of inflammatory cytokines. In addition, hTERT treatment improved cellular and nuclear morphology, in association with a normalization of the transcriptional profile, effects that may be mediated in part by a reduction in progerin expression and an increase in sirtuin 1 (SIRT1). Progeria mice treated with mTERT lentivirus manifested similar improvements, with a reduction in inflammatory and DNA damage markers and increased SIRT1 in their vasculature and other organs. Furthermore, mTERT therapy increased the lifespan of HGPS mice. CONCLUSION: Vascular rejuvenation using telomerase mRNA is a promising approach for progeria and other age-related diseases.

Difference of immune cell infiltration between stable and unstable carotid artery atherosclerosis.

Atherosclerotic plaque instability contributes to ischaemic stroke and myocardial infarction. This study is to compare the abundance and difference of immune cell subtypes within unstable atherosclerotic tissues. CIBERSORT was used to speculate the proportions of 22 immune cell types based on a microarray of atherosclerotic carotid artery samples. R software was utilized to illustrate the bar plot, heat map and vioplot. The immune cell landscape in atherosclerosis was diverse, dominated by M2 macrophages, M0 macrophages, resting CD4 memory T cells and CD8 T cells. There was a significant difference in resting CD4 memory T cells (p = 0.032), T cells follicular helper (p = 0.033), M0 (p = 0.047) and M2 macrophages (p = 0.012) between stable and unstable atherosclerotic plaques. Compared with stable atherosclerotic plaques, unstable atherosclerotic plaques had a higher percentage of M2 macrophages. Moreover, correlation analysis indicated that the percentage of naïve CD4 T cells was strongly correlated with that of gamma delta T cells (r = 0.93, p < 0.001), while memory B cells were correlated with plasma cells (r = 0.85, p < 0.001). In summary, our study explored the abundance and difference of specific immune cell subgroups at unstable plaques, which would aid new immunotherapies for atherosclerosis.

Surveillance of premalignant gastric cardia lesions: A population-based prospective cohort study in China.

In our study, we aimed to assess the long-term risk of gastric cardia adenocarcinoma (GCA) for patients with different histological cardia lesions to inform future guidelines for GCA screening in China. We conducted a population-based prospective study among 9740 subjects who underwent upper endoscopy screening during 2005 to 2009 and followed until December 2017. Cumulative incidence and mortality rates of GCA were calculated by the baseline histological diagnoses, and the hazard ratios (HRs), overall and by age and sex, were analyzed by Cox proportional hazards models. During a median follow-up of 10 years, we identified 123 new GCA cases (1.26%) and 31 GCA deaths (0.32%). The age-standardized incidence and mortality rates of GCA were 128.71/100 000 and 35.69/100 000 person-years, and cumulative incidence rate in patients with cardia high-grade dysplasia (CHGD), cardia low-grade dysplasia (CLGD) and atrophic carditis (AC)/cardia intestinal metaplasia (CIM) was 25%, 3.05% and 1.58%, respectively. The progression rate and cancer risk of GCA increased monotonically with each step in Correa's cascade. Individuals aged 50 to 69 years had 4.4 times higher GCA incidence than those aged 40 to 49 years. Patients with CLGD had a significantly higher 3-year GCA incidence than the normal group, while patients with AC/CIM had a comparable GCA risk during 3-year follow-up but a higher risk at 5-year intervals. Our results suggested a postponed starting age of 50 years for GCA screening, immediate treatment for patients with CHGD, a 3-year surveillance interval for patients with CLGD, and a lengthened surveillance interval of 5 years for patients with AC/CIM.

Colorectal cancer burden and trends: Comparison between China and major burden countries in the world.

OBJECTIVE: To summarize the colorectal cancer (CRC) burden and trend in the world, and compare the difference of CRC burden between other countries and China. METHODS: Incidence and mortality data were extracted from the GLOBOCAN2018 and Cancer Incidence in Five Continents. Age-specific incidence trend was conducted by Joinpoint analysis and average annual percent changes were calculated. RESULTS: About 1.85 million new cases and 0.88 million deaths were expected in 2018 worldwide, including 0.52 million (28.20%) new cases and 0.25 million (28.11%) deaths in China. Hungary had the highest age-standardized incidence and mortality rates in the world, while for China, the incidence and mortality rates were only half of that. CRC incidence and mortality were highly correlated with human development index (HDI). Unlike the rapid increase in Republic of Korea and the downward trend in Canada and Australia, the age-standardized incidence rates by world standard population in China and Norway were rising gradually. The age-specific incidence rate in the age group of 50-59 years in China was increasing rapidly, while in Republic of Korea and Canada, the fastest growing age group was 30-39 years. CONCLUSIONS: The variations of CRC burden reflect the difference of risk factors, as well as levels of HDI and screening (early detection activities). The burden of CRC in China is high, and the incidence of CRC continues to increase, which may lead to a sustained increase in the burden of CRC in China in the future. Screening should be expanded to control CRC, and focused on young people in China.

Development and validation of a Super learner-based model for predicting survival in Chinese Han patients with resected colorectal cancer.

OBJECTIVE: Improved prognostic prediction for patients with colorectal cancer stays an important challenge. This study aimed to develop an effective prognostic model for predicting survival in resected colorectal cancer patients through the implementation of the Super learner. METHODS: A total of 2333 patients who met the inclusion criteria were enrolled in the cohort. We used multivariate Cox regression analysis to identify significant prognostic factors and Super learner to construct prognostic models. Prediction models were internally validated by 10-fold cross-validation and externally validated with a dataset from The Cancer Genome Atlas. Discrimination and calibration were evaluated by Harrell concordence index (C-index) and calibration plots, respectively. RESULTS: Age, T stage, N stage, histological type, tumor location, lymph-vascular invasion, preoperative carcinoembryonic antigen and sample lymph nodes were integrated into prediction models. The concordance index of Super learner-based prediction model (SLM) was 0.792 (95% confidence interval: 0.767-0.818), which is higher than that of the seventh edition American Joint Committee on Cancer TNM staging system 0.689 (95% confidence interval: 0.672-0.703) for predicting overall survival (P < 0.05). In the external validation, the concordance index of the SLM for predicting overall survival was also higher than that of tumor-node-metastasis (TNM) stage system (0.764 vs. 0.682, respectively; P < 0.001). In addition, the SLM showed good calibration properties. CONCLUSIONS: We developed and externally validated an effective prognosis prediction model based on Super learner, which offered more reliable and accurate prognosis prediction and may be used to more accurately identify high-risk patients who need more active surveillance in patients with resected colorectal cancer.

Signatures within esophageal microbiota with progression of esophageal squamous cell carcinoma.

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is one of the dominant malignances worldwide, but currently there is less focus on the microbiota with ESCC and its precancerous lesions. METHODS: Paired esophageal biopsy and swab specimens were obtained from 236 participants in Linzhou, China. Data from 16S ribosomal RNA gene sequencing were processed using quantitative insights into microbial ecology (QIIME2) and R Studio to evaluate differences. The Wilcoxon rank sum test and Kruskal-Wallis rank sum test were used to compare diversity and characteristic genera by specimens and participant groups. Ordinal logistic regression model was used to build microbiol prediction model. RESULTS: Microbial diversity was similar between biopsy and swab specimens, including operational taxonomic unit (OTU) numbers and Shannon index. There were variations and similarities of esophageal microbiota among different pathological characteristics of ESCC. Top 10 relative abundance genera in all groups include Streptococcus, Prevotella, Veillonella, Actinobacillus, Haemophilus, Neisseria, Alloprevotella, Rothia, Gemella and Porphyromonas. Genus Streptococcus, Haemophilus, Neisseria and Porphyromonas showed significantly difference in disease groups when compared to normal control, whereas Streptococcus showed an increasing tendency with the progression of ESCC and others showed a decreasing tendency. About models based on all combinations of characteristic genera, only taken Streptococcus and Neisseria into model, the prediction performance was the ideal one, of which the area under the curve (AUC) was 0.738. CONCLUSIONS: Esophageal biopsy and swab specimens could yield similar microbial characterization. The combination of Streptococcus and Neisseria has the potential to predict the progression of ESCC, which is needed to confirm by large-scale, prospective cohort studies.

Effect of N-(2-aminoethyl) ethanolamine on hypertrophic scarring changes in vitro: Finding novel anti-fibrotic therapies.

Hypertrophic scars (HS) limit movement, decrease quality of life, and remain a major impediment to rehabilitation from burns. However, no effective pharmacologic therapies for HS exist. Here we tested the in vitro anti-fibrotic effects of the novel chemical N-(2-aminoethyl) ethanolamine (AEEA) at non-toxic concentrations. Scanning electron microscopy showed that AEEA markedly altered the structure of the extracellular matrix (ECM) produced by primary dermal fibroblasts isolated from a HS of a burn patient (HTS). Compression atomic force microscopy revealed that AEEA stiffened the 3D nanostructure of ECM formed by HTS fibroblasts. Western blot analysis in three separate types of primary human dermal fibroblasts (including HTS) showed that AEEA exposure increased the extractability of type I collagen in a dose- and time-dependent fashion, while not increasing collagen synthesis. A comparison of the electrophoretic behavior of the same set of samples under native and denaturing conditions suggested that AEEA alters the 3D structure of type I collagen. The antagonization effect of AEEA to TGF-ß1 on ECM formation was also observed. Furthermore, analyses of the anti-fibrotic effects of analogs of AEEA (with modified pharmacophores) suggest the existence of a chemical structure-activity relationship. Thus, AEEA and its analogs may inhibit HS development; further study and optimization of analogs may be a promising strategy for the discovery for effective HS therapies.

Analysis of risk factors for cervical lymph node metastasis of papillary thyroid microcarcinoma: a study of 268 patients.

BACKGROUND: To investigate the risk factors of cervical lymph node (LN) metastasis in papillary thyroid microcarcinoma (PTMC) patients. METHODS: We retrospectively analyzed the clinicopathologic data of all patients who received standard lobectomy for PTMC at our institution between October 2017 and January 2019. Central LNs were dissected in all patients. Lateral LNs were dissected if metastasis to the lateral LNs was suggested based on pre-op fine-needle aspiration biopsy. The relationship between variables available prior to surgery and cervical LN metastasis was examined using multivariate regression. RESULTS: Post-op pathologic examination revealed cervical LN metastasis in 79 (29.5%) patients. Seventy subjects had metastasis only to central LNs, and 4 (1.5%) patients had metastasis only to lateral LNs. Five patients had metastasis to both central and lateral LNs. In comparison to patients without cervical LN metastasis, those with LN metastasis were significantly younger (40.63 ± 13.07 vs. 44.52 ± 12.23 years; P = 0.021) and had significantly larger tumor diameter on pathology (6.7 ± 2.2 vs. 5.9 ± 2.4 mm; P = 0.010). Multivariate regression analysis identified the following independent risks for cervical LN metastasis: male sex (OR 2.362, 95%CI 1.261~4.425; P = 0.007), age (OR 0.977, 95%CI 0.956~0.999; P = 0.042) and ultrasound tumor diameter at > 5 mm (OR 3.172, 95%CI 1.389~7.240; P = 0.006). CONCLUSION: Cervical LN metastasis occurs in a non-insignificant proportion of PTMC patients. Independent risks included male sex, younger age and larger tumor diameter on ultrasound.

Two distinct cytokinesis pathways drive trypanosome cell division initiation from opposite cell ends.

Cytokinesis in Trypanosoma brucei, an early branching protozoan, occurs along its longitudinal axis uni-directionally from the anterior tip of the new flagellum attachment zone filament toward the cell's posterior end. However, the underlying mechanisms remain elusive. Here we report that cytokinesis in T. brucei is regulated by a concerted action of Polo-like kinase, Aurora B kinase, and a trypanosome-specific protein CIF1. Phosphorylation of CIF1 by Polo-like kinase targets it to the anterior tip of the new flagellum attachment zone filament, where it subsequently recruits Aurora B kinase to initiate cytokinesis. Consistent with its role, CIF1 depletion inhibits cytokinesis initiation from the anterior end of the cell, but, surprisingly, triggers cytokinesis initiation from the posterior end of the cell, suggesting the activation of an alternative cytokinesis from the opposite cell end. Our results reveal the mechanistic roles of CIF1 and Polo-like kinase in cytokinesis initiation and elucidate the mechanism underlying the recruitment of Aurora B kinase to the cytokinesis initiation site at late anaphase. These findings also delineate a signaling cascade controlling cytokinesis initiation from the anterior end of the cell and uncover a backup cytokinesis that is initiated from the posterior end of the cell when the typical anterior-to-posterior cytokinesis is compromised.

Single-Molecule Force Measurement Guides the Design of Multivalent Ligands with Picomolar Affinity.

Interaction of multiple entities and receptors, or multivalency is widely applied to achieve high affinity ligands for diagnostic and therapeutic purposes. However, lack of knowledge on receptor distribution in living subjects remains a challenge for rational structure design. Herein, we develop a force measurement platform to probe the distribution and separation of the cell surface vascular endothelial growth factor receptors (VEGFR) in live cells, and use this to assess the geometry of appropriate linkers for distinct multivalent binding modes. A tetravalent lead ZD-4, which was developed from an antitumor drug ZD6474 (Vandetanib) with combined hybrid binding effects, yielded a 2000-fold improvement in the binding affinity to VEGFR with IC50 value of 25 pm. We confirmed the improved affinity by the associated increase of tumor uptake in the VEGFR-targeting positron emission tomography (PET) imaging using U87 tumor xenograft mouse model.

Development of an Electroporation and Nanoparticle-based Therapeutic Platform for Bone Metastases.

Purpose To assess for nanopore formation in bone marrow cells after irreversible electroporation (IRE) and to evaluate the antitumoral effect of IRE, used alone or in combination with doxorubicin (DOX)-loaded superparamagnetic iron oxide (SPIO) nanoparticles (SPIO-DOX), in a VX2 rabbit tibial tumor model. Materials and Methods All experiments were approved by the institutional animal care and use committee. Five porcine vertebral bodies in one pig underwent intervention (IRE electrode placement without ablation [n = 1], nanoparticle injection only [n = 1], and nanoparticle injection followed by IRE [n = 3]). The animal was euthanized and the vertebrae were harvested and evaluated with scanning electron microscopy. Twelve rabbit VX2 tibial tumors were treated, three with IRE, three with SPIO-DOX, and six with SPIO-DOX plus IRE; five rabbit VX2 tibial tumors were untreated (control group). Dynamic T2*-weighted 4.7-T magnetic resonance (MR) images were obtained 9 days after inoculation and 2 hours and 5 days after treatment. Antitumor effect was expressed as the tumor growth ratio at T2*-weighted MR imaging and percentage necrosis at histologic examination. Mixed-effects linear models were used to analyze the data. Results Scanning electron microscopy demonstrated nanopores in bone marrow cells only after IRE (P , .01). Average volume of total tumor before treatment (503.1 mm3 ± 204.6) was not significantly different from those after treatment (P = .7). SPIO-DOX was identified as a reduction in signal intensity within the tumor on T2*-weighted images for up to 5 days after treatment and was related to the presence of iron. Average tumor growth ratios were 103.0% ± 75.8 with control treatment, 154.3% ± 79.7 with SPIO-DOX, 77% ± 30.8 with IRE, and -38.5% ± 24.8 with a combination of SPIO-DOX and IRE (P = .02). The percentage residual viable tumor in bone was significantly less for combination therapy compared with control (P = .02), SPIO-DOX (P , .001), and IRE (P = .03) treatment. The percentage residual viable tumor in soft tissue was significantly less with IRE (P = .005) and SPIO-DOX plus IRE (P = .005) than with SPIO-DOX. Conclusion IRE can induce nanopore formation in bone marrow cells. Tibial VX2 tumors treated with a combination of SPIO-DOX and IRE demonstrate enhanced antitumor effect as compared with individual treatments alone. © RSNA, 2017 Online supplemental material is available for this article.

A variant in KCNQ1 gene predicts metabolic syndrome among northern urban Han Chinese women.

BACKGROUND: Previous studies have reported that the potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene is associated with diabetes in both European and Asian population. This study aims to find a predictable single nucleotide polymorphism (SNP) to predict the risk of metabolic syndrome (MetS) through investigating the association of SNP in KCNQ1 gene with MetS in Han Chinese women of northern urban area. METHODS: Six SNPs were selected and genotyped in 1381 unrelated women aged 21 and above, who have had physical check-up in Shandong Provincial Qianfoshan Hospital. Cox proportional model was conducted to access the association between SNPs and MetS. RESULTS: Sixty one women developed MetS between 2010 and 2015 during the 3055 person-year of follow-up. The cumulative incidence density was 19.964/1000 person-year. The SNP rs163182 was associated with MetS both in the additive genetic model (RR = 1.658, 95% CI: 1.144-2.402) and in the recessive genetic model (RR = 2.461, 95% CI: 1.347-4.496). It remained significant after adjustment. This relationship was also observed in MetS components (BMI and SBP). CONCLUSION: A novel association between rs163182 and MetS was found in this study, which can predict the occurrence of MetS among northern urban Han Chinese women. More investigations are needed to be done to assess the possible pathway in which KCNQ1 gene affects MetS.

Development and validation of a nomogram for predicting survival in Chinese han patients with resected colorectal cancer.

BACKGROUND: Estimates of survival after curative colorectal cancer (CRC) surgery are the basis of patient care and treatment planning. A nomogram is a useful tool for individualized cancer prognosis. METHODS: A total of 2450 patients with nonmetastatic CRC were included to develop a nomogram. Prognostic factors were identified and integrated by the Cox proportional hazards model. Then, we developed and validated a prognostic nomogram. The performance of this model was assessed by the concordance index (C-index) and a calibration curve. The nomogram was internally validated by bootstrapping and externally validated with a separate database of 299 patients from The Cancer Genome Atlas. RESULTS: Age, T stage, N stage, histological type, tumor location, lymph-vascular invasion, preoperative carcinoembryonic antigen, and sample lymph nodes were integrated into the nomogram. The C-index of the nomogram for predicting overall survival was higher than that of the seventh edition American Joint Committee on Cancer TNM staging system (training data set, 0.76 vs 0.68, respectively; P < 0.001; validation data set, 0.78 vs 0.69, respectively; P = 0.003). CONCLUSION: We developed a prognostic nomogram for patients with nonmetastatic CRC, which could provide a more individualized outcome prognostication than that afforded by the TNM staging system by using common clinicopathologic factors.

A competing-risks nomogram for predicting probability of death from CRC in Chinese Han patients with Stage I-III CRC.

BACKGROUND: Many patients with colorectal cancer are elderly with competing comorbidities. When constructing nomogram for assessing survival, we should consider the influence of competing risk. A competing-risks nomogram was developed to estimate the probability of death due to colorectal cancer for patients after curative surgery. METHODS: A total of 2442 patients with non-metastatic colorectal cancer were included to develop competing-risks nomogram. Competing-risks nomogram were established based on the results of Fine and Gray competing-risks proportional hazards model. To maximize the accuracy of prediction, model selection was not carried out, and non-linear continuous variables were flexibly modeled with restricted cubic splines. The nomogram was internal-validated by bootstrapping, and externally validated with a separate database of 299 patients from The Cancer Genome Atlas. The performance of this model was assessed by concordance index and a calibration curve. RESULTS: There were 332 patients died of colorectal cancer and 46 died of other causes during the follow-up period. Age, T stage, N stage, histological type, tumor location, adjuvant chemotherapy, preoperative carcinoembryonic antigen, lymph vascular invasion, lymph node ratio and sample lymph nodes were integrated into competing-risks nomogram. The competing-risks nomogram for predicting probability of death due to colorectal cancer with a concordance index of 0.768, ameliorating the stratification provided by the seventh edition tumor-node-metastasis staging system of the American Joint Committee on Cancer (AJCC). The concordance index for validation dataset was 0.783. CONCLUSION: We developed and externally validated a competing-risks nomogram for Chinese Han patients with non-metastatic colorectal cancer, which could provide probability of death from colorectal cancer in the presence of competing risks.

Crosstalk between Smad2/3 and specific isoforms of ERK in TGF-ß1-induced TIMP-3 expression in rat chondrocytes.

This study investigated the roles of ERK1 and ERK2 in transforming growth factor-ß1 (TGF-ß1)-induced tissue inhibitor of metalloproteinases-3 (TIMP-3) expression in rat chondrocytes, and the specific roles of ERK1 and ERK2 in crosstalk with Smad2/3 were investigated to demonstrate the molecular mechanism of ERK1/2 regulation of TGF-ß1 signalling. To examine the interaction of specific isoforms of ERK and the Smad2/3 signalling pathway, chondrocytes were infected with LV expressing either ERK1 or ERK2 siRNA and stimulated with or without TGF-ß1. At indicated time-points, TIMP-3 expression was determined by real-time PCR and Western blotting; p-Smad3, nuclear p-Smad3, Smad2/3, p-ERK1/2 and ERK1/2 levels were assessed. And then, aggrecan, type II collagen and the intensity of matrix were examined. TGF-ß1-induced TIMP-3 expression was significantly inhibited by ERK1 knock-down, and the decrease in TIMP-3 expression was accompanied by a reduction of p-Smad3 in ERK1 knock-down cells. Knock-down of ERK2 had no effect on neither TGF-ß1-induced TIMP-3 expression nor the quantity of p-Smad3. Moreover, aggrecan, type II collagen expression and the intensity of matrix were significantly suppressed by ERK1 knock-down instead of ERK2 knock-down. Taken together, ERK1 and ERK2 have different roles in TGF-ß1-induced TIMP-3 expression in rat chondrocytes. ERK1 instead of ERK2 can regulate TGF-ß/Smad signalling, which may be the mechanism through which ERK1 regulates TGF-ß1-induced TIMP-3 expression.

Comparison of Lavage Techniques for Preventing Incision Infection Following Posterior Lumbar Interbody Fusion.

BACKGROUND The main purpose of this study was to compare the effects of various lavage techniques - traditional saline lavage (SL), pulse lavage (PL), closed drainage (CD), and iodine lavage (IL) - on preventing incision-related infection after posterior lumbar interbody fusion. MATERIAL AND METHODS Patients with prolapsed lumbar (intervertebral) discs (PLID) undergoing posterior lumbar interbody fusion surgery (PLIF) over the course of 2 years were included and were randomly allocated into 4 groups: the SL group, the PL group, the CD group, and the IL group. Relevant data were recorded, including preoperative conditions, intraoperative lavage time, lavage fluid volume, incision outlook, pain perception, results of routine blood tests, and postoperative infection rate. RESULTS The PL, CD, and IL groups showed less intraoperative lavage time, lavage volume fluid, effusion, infection rate, and muscle and lower pain perception compared with the SL group (all P<0.05). Significant differences in white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were observed between preoperative and postoperative data in each group (P<0.01). No significant differences in clinical characteristics, postoperative temperature, suture removal time, incision characteristics, WBC, ESR, and CRP were observed among the PL, CD, IL, and SL groups (P>0.05). CONCLUSIONS PL, CD, and IL all showed much better postoperative infection prevention in comparison to SL.