Combining bulk and scRNA-seq to explore the molecular mechanisms governing the distinct efferocytosis activities of a macrophage subpopulation in PDAC.

Pancreatic ductal adenocarcinoma (PDAC), a very aggressive tumour, is currently the third leading cause of cancer-related deaths. Unfortunately, many patients face the issue of inoperability at the diagnostic phase leading to a quite dismal prognosis. The onset of metastatic processes has a crucial role in the elevated mortality rates linked to PDAC. Individuals with metastatic advances receive only palliative therapy and have a grim prognosis. It is essential to carefully analyse the intricacies of the metastatic process to enhance the prognosis for individuals with PDAC. Malignancy development is greatly impacted by the process of macrophage efferocytosis. Our current knowledge about the complete range of macrophage efferocytosis activities in PDAC and their intricate interactions with tumour cells is still restricted. This work aims to resolve communication gaps and pinpoint the essential transcription factor that is vital in the immunological response of macrophage populations. We analysed eight PDAC tissue samples sourced from the gene expression omnibus. We utilized several software packages such as Seurat, DoubletFinder, Harmony, Pi, GSVA, CellChat and Monocle from R software together with pySCENIC from Python, to analyse the single-cell RNA sequencing (scRNA-seq) data collected from the PDAC samples. This study involved the analysis of a comprehensive sample of 22,124 cells, which were classified into distinct cell types. These cell types encompassed endothelial and epithelial cells, PDAC cells, as well as various immune cells, including CD4+ T cells, CD8+ T cells, NK cells, B cells, plasma cells, mast cells, monocytes, DC cells and different subtypes of macrophages, namely C0 macrophage TGM2+, C1 macrophage PFN1+, C2 macrophage GAS6+ and C3 macrophage APOC3+. The differentiation between tumour cells and epithelial cells was achieved by the implementation of CopyKat analysis, resulting in the detection and categorization of 1941 PDAC cells. The amplification/deletion patterns observed in PDAC cells on many chromosomes differ significantly from those observed in epithelial cells. The study of Pseudotime Trajectories demonstrated that the C0 macrophage subtype expressing TGM2+ had the lowest level of differentiation. Additionally, the examination of gene set scores related to efferocytosis suggested that this subtype displayed higher activity during the efferocytosis process compared to other subtypes. The most active transcription factors for each macrophage subtype were identified as BACH1, NFE2, TEAD4 and ARID3A. In conclusion, the examination of human PDAC tissue samples using immunofluorescence analysis demonstrated the co-localization of CD68 and CD11b within regions exhibiting the presence of keratin (KRT) and alpha-smooth muscle actin (α-SMA). This observation implies a spatial association between macrophages, fibroblasts, and epithelial cells. There is variation in the expression of efferocytosis-associated genes between C0 macrophage TGM2+ and other macrophage cell types. This observation implies that the diversity of macrophage cells might potentially influence the metastatic advancement of PDAC. Moreover, the central transcription factor of different macrophage subtypes offers a promising opportunity for targeted immunotherapy in the treatment of PDAC.

PlantNh-Kcr: a deep learning model for predicting non-histone crotonylation sites in plants.

BACKGROUND: Lysine crotonylation (Kcr) is a crucial protein post-translational modification found in histone and non-histone proteins. It plays a pivotal role in regulating diverse biological processes in both animals and plants, including gene transcription and replication, cell metabolism and differentiation, as well as photosynthesis. Despite the significance of Kcr, detection of Kcr sites through biological experiments is often time-consuming, expensive, and only a fraction of crotonylated peptides can be identified. This reality highlights the need for efficient and rapid prediction of Kcr sites through computational methods. Currently, several machine learning models exist for predicting Kcr sites in humans, yet models tailored for plants are rare. Furthermore, no downloadable Kcr site predictors or datasets have been developed specifically for plants. To address this gap, it is imperative to integrate existing Kcr sites detected in plant experiments and establish a dedicated computational model for plants. RESULTS: Most plant Kcr sites are located on non-histones. In this study, we collected non-histone Kcr sites from five plants, including wheat, tabacum, rice, peanut, and papaya. We then conducted a comprehensive analysis of the amino acid distribution surrounding these sites. To develop a predictive model for plant non-histone Kcr sites, we combined a convolutional neural network (CNN), a bidirectional long short-term memory network (BiLSTM), and attention mechanism to build a deep learning model called PlantNh-Kcr. On both five-fold cross-validation and independent tests, PlantNh-Kcr outperformed multiple conventional machine learning models and other deep learning models. Furthermore, we conducted an analysis of species-specific effect on the PlantNh-Kcr model and found that a general model trained using data from multiple species outperforms species-specific models. CONCLUSION: PlantNh-Kcr represents a valuable tool for predicting plant non-histone Kcr sites. We expect that this model will aid in addressing key challenges and tasks in the study of plant crotonylation sites.

Alleviated symptoms of SARS-CoV-2 Omicron variant infection in chronic hepatitis B patients with immune control.

The impact of hepatitis B virus (HBV) infection on the progression of coronavirus disease 2019 (COVID-19) disease remains controversial. We aimed to investigate whether pre-existing chronic HBV (CHB) infection and therapy with anti-HBV nucleos(t)ide analogs (NAs) influence the clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. In this study, clinical information was collected via a questionnaire from patients with COVID-19, and their clinical symptoms were quantitatively assessed for comparative analyses. Additionally, hepatitis B-related laboratory data were collected for CHB patients. Propensity score matching (PSM) was used to minimize confounding biases. A total of 785 patients with COVID-19 were included in the cohort, of which 387 were identified as being infected with CHB infection and they were categorized as being in the immune control or clearance phase. After PSM, the CHB group (n = 222) had a shorter duration of fever and disease course, milder clinical symptoms, and lower incidence of pneumonia than the non-CHB group (n = 222) after Omicron variant infection (p < 0.05). After the adjustment of confounding factors, CHB patients showed a lower risk of prolonged fever, severe clinical symptoms, and pneumonia (p < 0.05). However, there were no statistically significant differences in the clinical symptoms and incidence of pneumonia between CHB patients who received and did not receive NAs, or CHB patients who received tenofovir disoproxil fumarate and entecavir (p > 0.05). In conclusion, our findings suggest that the crosstalk of anti-HBV immunity may contribute to the alleviated symptoms of SARS-CoV-2 Omicron variants infection in the CHB patients, independent of anti-HBV NA therapy.

Is fatigue related to the severity of liver inflammation in patients with chronic liver disease? A cross-sectional study.

OBJECTIVES: Fatigue is common in patients with chronic liver disease; however, its pathogenesis is unclear. This study aimed to provide insights into the pathogenesis of chronic liver disease-related fatigue by assessing the relationship between fatigue and the degree of inflammation in chronic liver disease. DESIGN: We performed a cross-sectional study of 1374 patients with pathologically proven chronic liver disease diagnosed at the Affiliated Hospital of Hangzhou Normal University in Hangzhou, China. SETTING: Primary single-centre study. PARTICIPANTS: One thousand three hundred and seventy-four patients with liver biopsy-proven chronic liver disease. INTERVENTIONS: The patients were divided into fatigue and non-fatigue groups according to the Chronic Liver Disease Questionnaire. Propensity score matching was used to match the baseline features of the patients in the two groups. PRIMARY AND SECONDARY OUTCOME MEASURES: Liver steatosis, ballooning, inflammation and fibrosis were measured according to the pathological results of liver biopsy. Fatigue was measured using the Chronic Liver Disease Questionnaire. RESULTS: Of the 1374 patients, 262 (19.67%) experienced fatigue. There were 242 and 484 patients with and without fatigue, respectively, who were successfully matched for sex, age and classification of chronic liver disease by propensity score matching. After matching, the fatigue group showed higher liver enzyme levels, inflammation grades and fibrosis stages than the non-fatigue group (p<0.05). Multivariate analysis showed that age (OR: 2.026; p=0.003), autoimmune liver disease (OR: 2.749; p=0.002) and active inflammation (OR: 1.587; p=0.003) were independent risk factors for fatigue after adjusting for confounders. The OR of the risk for fatigue increased in a stepwise manner with increasing inflammation grade in young-aged and middle-aged patients (p<0.05). This tendency was not observed in elderly patients (p>0.05). CONCLUSION: Patients with chronic liver disease were burdened by fatigue, which increased progressively with rising liver inflammation severity in young-aged and middle-aged rather than elderly patients.

The prognostic nutritional index represents a novel inflammation-nutrition-based prognostic factor for nasopharyngeal carcinoma.

Purpose: This study explored the relationship between the prognostic nutritional index (PNI) and overall survival rate (OS) in patients with nasopharyngeal carcinoma (NPC), and established and validated an effective nomogram to predict clinical outcomes. Methods: This study included 618 patients newly diagnosed with locoregionally advanced NPC. They were divided into training and validation cohorts at a ratio of 2:1 based on random numbers. The primary endpoint of this study was OS, progression-free survival (PFS) was the second endpoint. A nomogram was drawn from the results of multivariate analyses. Harrell's concordance index (C-index), area under the receiver operator characteristic curve (AUC), and decision curve analysis (DCA) were used to evaluate the clinical usefulness and predictive ability of the nomogram and were compared to the current 8th edition of the International Union Against Cancer/American Joint Committee (UICC/AJCC) staging system. Results: The PNI cutoff value was 48.1. Univariate analysis revealed that age (p < 0.001), T stage (p < 0.001), N stage (p = 0.036), tumor stage (p < 0.001), PNI (p = 0.001), lymphocyte-neutrophil ratio (NLR, p = 0.002), and lactate dehydrogenase (LDH, p = 0.009) were significantly associated with OS, age (p = 0.001), T-stage (p < 0.001), tumor stage (p < 0.001), N-stage (p = 0.011), PNI (p = 0.003), NLR (p = 0.051), and LDH (p = 0.03) were significantly associated with PFS. Multivariate analysis showed that age (p < 0.001), T-stage (p < 0.001), N-stage(p = 0.02), LDH (p = 0.032), and PNI (p = 0.006) were significantly associated with OS, age (p = 0.004), T-stage (<0.001), N-stage (<0.001), PNI (p = 0.022) were significantly associated with PFS. The C-index of the nomogram was 0.702 (95% confidence interval [CI]: 0.653-0.751). The Akaike information criterion (AIC) value of the nomogram for OS was 1142.538. The C-index of the TNM staging system was 0.647 (95% CI, 0.594-0.70) and the AIC was 1163.698. The C-index, DCA, and AUC of the nomogram demonstrated its clinical value and higher overall net benefit compared to the 8th edition of the TNM staging system. Conclusion: The PNI represents a new inflammation-nutrition-based prognostic factor for patients with NPC. In the proposed nomogram, PNI and LDH were present, which led to a more accurate prognostic prediction than the current staging system for patients with NPC.

Liver fibrosis is closely related to metabolic factors in metabolic associated fatty liver disease with hepatitis B virus infection.

This case-control study aimed to identify the clinical characteristics and explore the risk factors for liver fibrosis in metabolic associated fatty liver disease (MAFLD) patients with hepatitis B virus (HBV) infection. The patients were grouped into MAFLD + HBV and MAFLD (without HBV infection). Propensity score matching (PSM) was used to match baseline features between the groups. We included 401 patients with biopsy-proven MAFLD, 179 of whom had HBV infection. A total of 83 pairs were successfully matched via PSM, and steatosis scores and ballooning in the MAFLD + HBV group were lower than those in the MAFLD group, while the inflammation scores and liver fibrosis stages were higher. After adjusted for confounding factors, HBV infection was associated with a higher risk of significant liver fibrosis in patients with MAFLD [odds ratio (OR): 3.140, P = 0.003]. Overall, 43.58% (78/179) of patients in the MAFLD + HBV group had significant liver fibrosis. Further multivariate regression analysis, hypertension (OR: 2.640; P = 0.031), type 2 diabetes (OR: 4.939; P = 0.035), and elevated glutamyl-transferase levels (OR: 3.980; P = 0.001) were risk factors for liver fibrosis in the MAFLD + HBV group. This suggests metabolic rather than viral factors are more closely associated with liver fibrosis in MAFLD patients with HBV infection.

Blood pressure stratification for predicting liver fibrosis risk in metabolic dysfunction associated fatty liver disease.

INTRODUCTION AND OBJECTIVES: The optimal blood pressure (BP) range for patients with metabolic dysfunction-associated fatty liver disease (MAFLD) is currently unknown. This study aimed to explore the relationship between stratified BP levels and MAFLD progression. PATIENTS AND METHODS: The data of adults who underwent yearly health check-ups were screened to establish both a cross-sectional and a 6-year longitudinal cohort of individuals with MAFLD. BP was classified into the following categories optimal, normal, high-normal, and hypertension. Liver fibrosis was diagnosed with fibrosis-4 (FIB-4) score, nonalcoholic fatty liver disease fibrosis score (NFS), and aspartate aminotransferase-to-platelet ratio index (APRI). RESULTS: A total of 10,232 individuals were included in the cross-sectional cohort. In the MAFLD population, individuals with liver fibrosis had significantly higher BP levels and hypertension prevalence (P < 0.001) than those without. Furthermore, liver fibrosis score was significantly associated with BP levels (P < 0.001). In the 6-year longitudinal cohort of 3661 individuals with MAFLD without liver fibrosis, the incidence rates of liver fibrosis increased with increasing BP levels as follows optimal=11.20%, normal=13.90%, high-normal=19.50%, hypertension=26.20% (log-rank 22.205; P < 0.001). Cox regression analysis showed that both baseline high-normal BP (hazard ratio [HR], 1.820; P=0.019) and hypertension (HR, 2.656; P < 0.001) were predictive of liver fibrosis. CONCLUSIONS: BP stratification may be useful in predicting the progression of MAFLD. Individuals having MAFLD with concurrent hypertension or high-normal BP are at a higher risk of liver fibrosis. These findings may provide a criteria for early intervention of MAFLD to prevent liver fibrosis.

Utilization of Waste Amine-Oxime (WAO) Resin to Generate Carbon by Microwave and Its Removal of Pb(II) in Water.

Utilising waste amine-oxime (WAO) resin through microwave semi-carbonization, a carbon adsorbent (CA) was obtained to remove Pb(II). After microwave treatment, the pore size of the skeleton structure, three-dimensional porous network, and lamellar pore structure of WAO was improved. The distribution coefficient (Kd) of Pb(II) onto CA is 620 mL/g, and the maximum adsorption capacity of Pb(II) is 82.67 mg/g after 20 min of WAO microwave treatment. The adsorption kinetics and adsorption isotherms conform to the quasi-second-order kinetic equation and Langmuir adsorption isotherm model, respectively. The surface of MT-WAO is negatively charged and the adsorption mechanism is mainly electrostatic interaction. Pb(II) elution in hydrochloric acid solution is more than 98%, and its recovery is high at 318 K and for 1 h.

Observation of the cervical microbiome in the progression of cervical intraepithelial neoplasia.

OBJECTIVE: Cervical microbial community in the cervical intraepithelial neoplasia and cervical cancer patients was analysed to study its composition, diversity and signalling pathways by high-throughput 16S rDNA sequencing,and the candidate genes associated with occurrence and progression of cervical intraepithelial neoplasia were screened out and the model was established to predict the evolution of cervical intraepithelial neoplasia malignant transformation from the cervical microbial genes aspect. METHODS: Cervical tissues of normal, cervical intraepithelial neoplasia and cervical cancer patients without receiving any treatment were collected. The correlation between candidate genes and cervical intraepithelial neoplasia progression was initially determined by analyzing the microbial flora. Real-time fluorescence quantitative PCR was used to detect the expression of candidate genes in different cervical tissues, ROC curve and logistic regression was used to analyse and predict the risk factors related to the occurrence and progression of cervical intraepithelial neoplasia. Finally, the early warning model of cervical intraepithelial neoplasia occurrence and progression is established. RESULTS: Cervical tissues from normal, cervical intraepithelial neoplasia and cervical cancer patients were collected for microbial community high-throughput 16S rDNA sequencing. The analysis revealed five different pathways related to cervical intraepithelial neoplasia. 10 candidate genes were selected by further bioinformatics analysis and preliminary screening. Real time PCR, ROC curve and Logistic regression analysis showed that human papillomavirus infection, TCT severity, ABCG2, TDG, PCNA were independent risk factors for cervical intraepithelial neoplasia. We used these indicators to establish a random forest model. Seven models were built through different combinations. The model 4 (ABCG2 + PCNA + TDG) was the best early warning model for the occurrence and progression of CIN. CONCLUSIONS: A total of 5 differential pathways and 10 candidate genes related to occurrence and progression of cervical intraepithelial neoplasia were found in cervical microbial community. This study firstly identified the genes from cervical microbial community that play an important role in the occurrence and progression of cervical intraepithelial neoplasia. At the same time, the early warning model including ABCG2 + PCNA+TDG genes provided a new idea and target for clinical prediction and blocking the evolution of cervical intraepithelial neoplasia malignant transformation from the aspect of cervical microbiological related genes.

Efficacy of Chemotherapy in Survival of Stage I Nasopharyngeal Carcinoma.

PURPOSE: To identify whether chemoradiotherapy improves survival of stage I nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: NPC patients were extracted from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. Pathologically confirmed stage T1N0M0 (the 7th edition AJCC) were investigated. Overall survival (OS) and cancer-specific survival (CSS) were compared between the radiotherapy and chemoradiotherapy groups using the Kaplan-Meier method and propensity score matching (PSM) analyses. RESULTS: This study included 91 (40.27%) patients in the chemoradiotherapy group and 135 (59.73%) patients in the radiotherapy group. Before PSM, chemoradiotherapy was associated with worse 3-year OS (74.31 vs 87.23%; P = 0.025) and 5-year OS (64.28 vs 83.12%; P = 0.001) compared to those associated with radiotherapy. Similarly, chemoradiotherapy showed worse 3-year CSS (87.01 vs 96.97%; P = 0.028) and 5-year CSS (80.39 vs. 96.97%; P = 0.002) than those of radiotherapy. After PSM, chemoradiotherapy revealed worse 5-year OS (63.10 vs. 82.49%; P = 0.031) and CSS (80.95 vs. 93.70%; P = 0.016) than radiotherapy. The multivariate regression analysis revealed that chemoradiotherapy was an independent risk prognostic factor for OS and CSS before and after PSM. CONCLUSION: Radiotherapy alone is recommended for stage I NPC patients.

Alagille syndrome caused by NOTCH2 mutation presented atypical pathological changes.

BACKGROUND: Alagille syndrome (ALGS) is a rare multisystem disorder caused by mutations in the JAG1 or NOTCH2 gene. However NOTCH2 gene mutations were rarely found in the Alagille patients. Little is known about the clinical and pathological profiles about Alagille patients with NOTCH2 mutation. CASE REPORT: Our case described a 16-year-old female patient manifesting as recurrent jaundice and abnormal liver function from the second week of her birth. She presented a butterfly vertebrae and typical facial features including a prominent forehead, deep-set eyes, a pointed chin, and a straight nose with bulbous tip. Pathogenic heterozygous c.5857 C > T variant in NOTCH2 gene was found. Her liver biopsy featured by a disorder liver structure with cholestasis and fibrosis in portal area, which is different from typical bile duct paucity reported in JAG1 deficient patients. RESULTS: A diagnosis of ALGS was made. The patient was treated with ursodeoxycholic acid and compound embryonic bovine liver extract tablets and infusion of human serum albumin to improve her clinical and pathological symptoms. CONCLUSION: Since Alagille patients with NOTCH2 mutations have been rarely reported, our case will highlight the clinical and pathological profiles of these patients.

Retropharyngeal lymph node metastasis on N stage of nasopharyngeal carcinoma.

PURPOSES: To evaluate retropharyngeal lymph node metastasis on N stage of nasopharyngeal carcinoma (NPC). METHODS: NPC patients were extracted from the Surveillance, Epidemiology, and End Results database between 2004 and 2016. Pathologically confirmed patients with complete data of retropharyngeal lymph node metastasis were investigated. The included patients were divided into N1a and N1b groups. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method and propensity score matching (PSM) analyses. RESULTS: This retrospective cohort study examined 759 patients: 70 who were stage N1a and 689 who were stage N1b. Before PSM, N1a group was associated with similar 5-year OS (77.7% vs. 72.4%; P = 0.15) and CSS (85.6% vs. 79.9%; P = 0.09) compared to N1b group. After PSM, a similar OS (75.0% vs. 60.7%; P = 0.12) was found between the radiotherapy and chemoradiotherapy groups. However, N1a group showed a better 5-year CSS (83.8% vs. 71.1%; P = 0.04) compared to N1b group. Stage N1b was an independent risk prognostic factor for CSS (hazard ratio = 2.54, 95% confidence interval: 1.02-6.34; P = 0.04). CONCLUSIONS: OS was not different between N1a and N1b groups. Retropharyngeal lymph node metastasis defined as stage N1 of the 8th edition American Joint Committee on Cancer staging system is reasonable.

Prognostic Nomogram For Locoregionally Advanced Nasopharyngeal Carcinoma.

The TNM staging system of NPC is the most important model for survival prediction. However, this model does not consider the biological variability of the tumor itself. This study aimed to develop a nomogram for predicting the overall survival of loco-regionally advanced nasopharyngeal carcinoma. 487 Patients with confimed nasopharyngeal carcinoma who underwent IMRT and chemotherapy were included in this study. We established prognostic nomogram for overall survival (OS) based on the Cox proportional hazards model. The predictive accuracy and discriminative ability were measured using the concordance index (C-index) and calibration curve. Nomogram was validated externally by assessing discrimination and calibration using an independent data set. Continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to analyze whether nomogram improve the prediction of survival than TNM stage system. Recursive partitioning analysis (RPA) was performed to stratifying risk of patients. Age, T-stage, N-stage, NLR, LDH were included in the nomogram for OS. The C-index of the nomogram for OS were 0.726 (95% CI, 0.690 to 0.762); The calibration curve showed the nomogram was able to predict 5-year OS accurately. The nomogram had a higher C-index than the TNM stage system (0.726 VS 0.632, P-value < 0.001). The NRI was 0.235 (95% CI: 0.129 to 0.396, P < 0.001), the IDI was 0.079 (95% CI: 0.034 to 0.396, p < 0.001). RPA was performed to stratify patients into three risk group, OS was significantly different between all three risk groups. High risk groups can be benefited survival from adjuvant chemotherapy. The nomogram outperformed the TNM staging system in predicting the OS of loco-regionally advanced nasopharyngeal carcinoma underwent intensity modulated radiation therapy and chemotherapy.

Cryobacterium soli sp. nov., isolated from forest soil.

A taxonomic study was performed on strain GCJ02T, which was isolated from forest soil from Baishan City, PR China. The bacterium was Gram-stain-positive, catalase-positive and weakly oxidase-positive, rod-shaped and non-motile. Growth was observed at salinities of 0-6.0 % and at temperatures of 4-26 °C. Phylogenetic analysis based on 16S rRNA gene sequences indicated that GCJ02T represented a member of the genus Cryobacterium, with the highest sequence similarity to Cryobacterium arcticum SK1T (99.5 %) and Cryobacterium zongtaii TMN-42T (99.5 %), followed by Cryobacterium psychrotolerans CGMCC 1.5382T (97.7 %), and other species of the genus Cryobacterium (96.4-96.9 %). The ANI and the DNA-DNA hybridization estimate values between GCJ02T and all type strains of species of the genus Cryobacterium were 72.5-84.5 % and 19.6-28.7 %, respectively. The principal fatty acids (>10 %) of GCJ02T were anteiso-C15 : 0(53.0 %) and anteiso-C17 : 0 (18.8 %). The G+C content of the chromosomal DNA was 68.4 mol%. The respiratory quinone was determined to be MK-10. Phosphatidylglycerol, diphosphatidylglycerol, glycolipid, and one unidentified phospholipid and three unidentified polar lipid were present. The combined genotypic and phenotypic data indicated that strain GCJ02T represents a novel species within the genus Cryobacterium, for which the name Cryobacterium soli sp. nov. is proposed, with the type strain GCJ02T (=MCCC 1K03549T=JCM 32391T).

Predictors for improvement of xerostomia in nasopharyngeal carcinoma patients receiving intensity-modulated radiotherapy.

To identify predictors for improvement of xerostomia in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT).Patients diagnosed with stage I-IVb NPC (according to the 7th edition of the American Joint Committee on Cancer) between September 2015 and March 2016 were retrospectively analyzed. All the patients received IMRT. Predictors for improvement of xerostomia were analyzed using logistic regression analysis. Receiver operating characteristic curve analysis was used to identify the most appropriate cut-off values for predicting factors.This study included 195 patients: xerostomia improved in 109 patients and xerostomia remained unchanged in 86 patients. Volume of the parotid gland ≤52.2 cm was a risk factor for xerostomia improvement (odds ratio [OR] = 3.506, 95% confidence interval [CI]: 1.932-6.362, P = .001). The mean dose of <39 Gy to the ipsilateral parotid gland was a protective factor (OR = 0.417, 95% CI: 0.271-0.641, P = .001). V30 of the contralateral parotid gland ≤52% was a protective factor (OR = 0.593, 95% CI: 0.462-0.760, P = .001).Volume of the parotid gland, the mean dose of the ipsilateral parotid gland, and V30 of the contralateral parotid gland were independent predictors for improvement of xerostomia.

B Lymphocytes Are the Target of Mesenchymal Stem Cells Immunoregulatory Effect in a Murine Graft-versus-Host Disease Model.

There is growing clinical interest in the utilization of mesenchymal stem cells (MSCs) in the management of acute graft-versus-host disease (aGvHD), yet the effect of major histocompatibility complexes (MHCs) on B lymphocytes in this process has been less well documented. Working in an MHC fully mismatched murine aGvHD model, we found that MSC co-transfer significantly prolonged the survival time of the recipients. More interestingly, analysis on immunophenotypic profiles of posttransplant splenocytes showed that surface expression of CD69 (an early activation marker) and CD86 (a costimulatory molecule) was suppressed predominantly on donor derived B lymphocytes by MSC infusion. Additionally, mRNA level of interleukin-4, a potent B lymphocyte stimulator, was strikingly reduced from MSC-treated mice, while interleukin-10, the regulatory B lymphocytes inductor, was increased; these may underlie the lesser activation of B lymphocytes. In consistence, depletion of B lymphocytes in the transfusion inoculum further prolonged the survival time of aGvHD mice regardless of MSC administration. Therefore, B lymphocytes played an important role in the development of aGvHD, and they are targets in MSC-regulated immune response cascade in vivo. This study may provide a mechanistic clue for the treatment of human clinical aGvHD.

Predictive factors of chemotherapy use in stage II nasopharyngeal carcinoma: A retrospective cohort study.

Identification of predictive factors of chemotherapy use and assessment of the roles of these factors in prognosis will aid therapeutic decision-making in stage II nasopharyngeal carcinoma (NPC).Using logistic regression, we retrospectively assessed factors predicting chemotherapy use in 251 stage II (2010  UICC/AJCC staging system) NPC patients. Five-year overall survival (OS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed based on the predictive factors.Logistic regression found that N1 stage was an independent factor predicting chemotherapy use in stage II NPC patients. However, 5-year OS (96.5% vs 94.9%, P = .564), LRFS (98.2% vs 96.9%, P = .652), and DMFS (95.9% vs 97.6%, P = .560) did not differ between N0 and N1 stage patients. Moreover, addition of chemotherapy use did not improve treatment outcomes in N1 stage compared with radiotherapy alone.N1 stage predicted chemotherapy use in stage II NPC patients. But, the addition of chemotherapy did not provide a survival benefit.

Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in intensity modulated radiation therapy for nasopharyngeal carcinoma.

BACKGROUND: Inflammatory response markers plays an important role in tumor progression. The aim of this analysis was to evaluate whether the neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) could predict the prognosis of nasopharyngeal carcinoma(NPC). MATERIALS AND METHODS: 247 patients who underwent Intensity Modulated Radiation Therapy( IMRT )were enrolled from January 2012 and December 2012. NLR, and PLR were calculated from peripheral blood cell counts taken at pre-treatment. Optimal cutoff values of NLR and PLR were determined on the basis of receiver operating characteristic curve analysis. Overall survival (OS), progression-free survival(PFS), distant metastasis-free survival (DMFS) and loco-regional recurrence-free survival ( LRFS) rates were compared according to NLR and PLR level respectively. Multivariate analysis was performed to assess the prognostic value of NLR and PLR. RESULTS: The 5-year estimated OS, PFS, LRFS and DFS were 87.2, 77.8, 96.9, and 86.2%, respectively. Our results shows that the NLR was significantly associated with T-stage (P < 0.05), N-stage (P < 0.05) and tumor stage(P < 0.05). PLR was significantly associated with T-stage (P < 0.05) and tumor stage(P < 0.05). NLR was an independent prognostic indicator for OS (HR: 3.259, P = 0.004), PFS (HR:7.093, P < 0.001), DMFS (HR: 6.576, P = 0.003), except for PLR. In subgroup analysis, adjuvant chemotherapy had no significantly improved survival for patients with high NLR. CONCLUSIONS: NLR is a strong prognostic factor for NPC patients. NLR might not be a useful indicator for selection of treatment strategies for loco-regionally advanced NPC.

Discovery of microarray-identified genes associated with the progression of cervical intraepithelial neoplasia.

OBJECTIVE: To identify genes potentially associated with cervical intraepithelial neoplasia (CIN) progression through bioinformatic approaches and clinicopathological verification. METHODS: mRNA expression microarray data related to CIN progression were screened from the Gene Expression Omnibus (GEO) database and re-analyzed using bioinformatics approaches. Tissue microarray immunohistochemistry was conducted to assess the significant identified genes in CIN, cervical cancer, and normal tissues. RESULTS: Biological annotation and text mining showed that 14 differentially expressed genes were directly or indirectly related to CIN progression. The expression of 5 up-regulated differentially expressed genes, namely, CCND2, TGFBR2, PRKCB, SH3KBP1 and WNT2B, was examined by tissue microarray immunohistochemistry, with the known CIN progression genes P16 and Ki-67 as the internal reference. Expression of TGFBR2, SH3KBP1, and WNT2B were not detected in CIN and cervical carcinoma, whereas no significant difference in the expression rate of PRKCB was detected (P > 0.05). CCND2, P16, and Ki-67 expression showed a gradual increasing trend in normal, CIN, and cervical cancer. CONCLUSIONS: 14 differentially expressed genes were associated with CIN progression, as indicated by the microarray data analysis results. CCND2 may be a new marker for the prediction of CIN progression in addition to P16 and Ki-67.