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.

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.

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.

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.

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).

Distribution of Chlamydia Trachomatis Genotypes in Infective Diseases of the Female Lower Genital Tract.

The purpose of this study was to investigate the distribution of Chlamydia trachomatis (CT) genotypes in infective diseases of the female lower genital tract, especially in cervical diseases. This study included 128 CT-positive women. DNA was extracted from cervical swabs. Omp1 gene PCR-RFLP and sequencing were used to confirm the subtypes of CT. The association of subtypes with age, clinical symptoms, cervical cytology, and biopsy results was further analyzed. Omp1 gene PCR-RFLP and sequencing showed that the order of prevalent CT genotypes in the female lower genital tract was D (n=38, 29.69%), followed by E (n=28, 21.88%), G (n=21, 16.41%), and F (n=16,12.50%). Genotypes J, H, and K were comparatively rare. Genotype I was not identified in our samples. Further analysis showed that patients with genotype G were more frequently co-infected with other bacteria. Genotype G was also associated with mucopurulent cervicitis (MPC) and cervical intraepithelial neoplasia (CIN). Patients with genotype E were commonly co-infected with HR-HPV. Although genotype D was the most prevalent, it was a relatively low-risk type. These results provide information on distribution of CT genotypes in infective diseases of the female lower genital tract, which is instrumental to developing a vaccine for CT.

Comparison of the short-term and long-term outcomes of laparoscopic hysterectomies and of abdominal hysterectomies: a case study of 4,895 patients in the Guangxi Zhuang Autonomous Region, China.

BACKGROUND: To evaluate the short-term and long-term outcomes after laparoscopic hysterectomy (LH) compared with abdominal hysterectomy (AH) in case of benign gynecological disease. METHODS: A multi-center cohort retrospective comparative study of population among 4,895 hysterectomies (3,539 LH vs.1,356 AH) between 2007 and 2013 was involved. Operative time (OT), estimated blood loss (EBL), intra-operative and post-operative complications, passing flatus; days with indwelling catheter, questionnaires covering pelvic floor functions and sexual functions were assessed. RESULTS: The EBL (174.1±157.4 vs. 263.1±183.2 cc, LH and AH groups, respectively), passing flatus (38.7±14.1 vs. 48.1±13.2 hours), days with indwelling catheter (1.5±0.6 vs. 2.2±0.8 days), use of analgesics (6.5% vs. 73.1%), intra-operative complication rate (2.4% vs. 4.1%), post-operative complication rate (2.3% vs. 5.7%), post-operative constipation (12.1% vs. 24.6%), mild and serious stress urinary incontinence (SUI) post-operative (P<0.001; P=0.014), and proportion of Female Sexual Functioning Index (FSFI) total score <26.55 post-operative (P<0.001) of the LH group were significantly less than those of AH group. There were no significant differences in OT (106.5±34.5 vs. 106.2±40.3 min) between the two groups. CONCLUSIONS: LH is a safe and efficient operation for improving patients?long-term quality of life (QoL), and LH is a cost-effectiveness procedure for treating benign gynecological disease. LH is superior to AH due to reduced EBL, reduced post-operative pain and earlier passing flatus.

CCR7 guides migration of mesenchymal stem cell to secondary lymphoid organs: a novel approach to separate GvHD from GvL effect.

Inefficient homing of systemically infused mesenchymal stem cells (MSCs) limits the efficacy of existing MSC-based clinical graft-versus-host disease (GvHD) therapies. Secondary lymphoid organs (SLOs) are the major niches for generating immune responses or tolerance. MSCs home to a wide range of organs, but rarely to SLOs after intravenous infusion. Thus, we hypothesized that targeted migration of MSCs into SLOs may significantly improve their immunomodulatory effect. Here, chemokine receptor 7 (CCR7) gene, encoding a receptor that specifically guides migration of immune cells into SLOs, was engineered into a murine MSC line C3H10T1/2 by retrovirus transfection system (MSCs/CCR7). We found that infusion of MSCs/CCR7 potently prolonged the survival of GvHD mouse model. The infused MSCs/CCR7 migrate to SLOs, relocate in proximity with T lymphocytes, therefore, potently inhibited their proliferation, activation, and cytotoxicity. Natural killer (NK) cells contribute to the early control of leukemia relapse. Although MSCs/CCR7 inhibited NK cell activity in vitro coculture, they did not impact on the proportion and cytotoxic capacities of NK cells in the peripheral blood of GvHD mice. In an EL4 leukemia cell loaded GvHD model, MSCs/CCR7 infusion preserved the graft-versus-leukemia (GvL) effect. In conclusion, this study demonstrates that CCR7 guides migration of MSCs to SLOs and thus highly intensify their in vivo immunomodulatory effect while preserving the GvL activity. This exciting therapeutic strategy may improve the clinical efficacy of MSC based therapy for immune diseases.

[Comparison of the short-term and long-term outcomes after laparoscopic surgery for early-stage endometrial cancer].

OBJECTIVE: To evaluate the short- term and long- term outcomes after laparoscopic surgery compared with traditional laparotomy in patients with stage I-II endometrial cancer. METHODS: A retrospective study of population among 673 patientsfor early-stage endometrial cancer between Jan. 2007 and May 2014 was involved from 6 third-grade class-A communal hospitals in Guangxi. Three hundred and seventy-six cases were performed by laparoscopy, 297 cases by laparotomy. The t-test and χ(2) test was used to compare the short-term and long-term outcomes. The short-term outcomes including surgical related outcomes and operative complications, the long- term outcomes including quality of life (pelvic floor functions and sexual functions), survival analysis and recurrence. The International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Sympotom (ICIQ- FLUTS) and the Female Sexual Function Index (FSFI) were used to assess pelvic floor function and sexual function. Survival rates were estimated by Kaplan-Meier analysis. The survival curves were compared by log-rank test. Cox regression analysis was used to select the risk factors for prognosis. RESULTS: (1) The short-term outcomes: There were significant difference in operative time [(258±71) vs (226±69) minutes], estimated blood loss [(343± 211) vs (491±411) ml], anus exhausting time [(2.3±0.9) vs (2.9±1.0) days], preserved days of installing catheter [(7 ± 5) vs (10±8) days], post- operative length of stay [(12 ± 7) vs (18 ± 12) days] between laparoscopic group andlaparotomy group (all P <0.05). While, there was no significant difference in lymph nodes yielded (21±8 vs 21±11; P>0.05),the intra-operative complications occurred [8.5%(32/376) vs 10.4%(31/297); P>0.05], and the post-operative complications [18.1% (68/376) vs 22.2% (66/297); P>0.05] between laparoscopic group and laparotomy group. However, the complications of vascular injury and the poor wound healing in laparoscopic group were respectively lower than those in laparotomy group [1.9%(7/376) vs 5.4% (16/297), P=0.003; and 0.3% (1/376) vs 4.7% (14/297), P<0.01]. (2) The long- term outcomes: There were no significant differences in overall survival (OS) and the degree of incontinence in ICIQ-FLUTS questionnaire between the two groups (all P >0.05). The sexual desire and sexual satisfaction scores dimension after 12 months of post- operative in FSFI questionnaire in the laparoscopic group were higher than those in laparotomy group (all P <0.05). However, there were no significant differences in sexual arousal, vaginal lubrication, orgasm and sexual pain dimension scores between the two groups (all P >0.05). The recurrence rate was 12.0%(45/376) in laparoscopic group and 14.5%(43/297) in laparotomy group (P= 0.269). The 5-year OS was 89.5% in the laparoscopic group and 87.2% in the open group (P >0.05) , and the 5-year free-progression survival rate was 87.9% in the laparoscopic group and 85.1% in the open group (P >0.05). (3) Prognostic factors in laparoscopic group: The univariate analysis shown that pathological type, surgical pathological staging, deep myometrial invasion, and retroperitoneal lymph node-positive were significantly affected prognosis in laparoscopic group (all P<0.01). The multivariate analyses showed that pathological type and surgical pathological stage were the independent prognostic factors (all P<0.01). CONCLUSIONS: Laparoscopy could reduce estimated blood loss, accelerate postoperative recovery and improve the quality of life after surgery compared to laparotomy, also ensure the same oncologically results as that by laparotomy. So, laparoscopic approach is a safe and effective treatment method for early- stage endometrial cancer.

Pharmacological characteristics and efficacy of a novel anti-angiogenic antibody FD006 in corneal neovascularization.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a key angiogenic factors. It plays an important role in both physiologic and pathologic angiogenesis and increases permeability across the vessels. Using antibody phage display technology, we obtained a novel anti-VEGFA IgG, named as FD006. In this study, the pharmacological characteristics and efficacy of FD006 in corneal neovascularization (CoNV) were evaluated. RESULTS: FD006 was predicted to have similar binding mode to bevacizumab. Experimental analysis showed that the binding ability of FD006 seemed a little stronger than bevacizumab, for the EC50 of FD006 to bind VEGF analyzed by ELISA was about 0.037 µg/mL while that of bevacizumab was 0.18 µg/mL. Binding kinetics assays showed similar results that FD006 possessed 2-fold higher affinity to bind VEGF than bevacizumab due to slower dissociation rate of FD006; meanwhile, FD006 inhibited the VEGF-induced proliferation of HUVEC with an IC50 value of 0.031 ± 0.0064 µg/ml, which seemed similar or a litter better than bevacizumab (0.047 ± 0.0081 µg/ml). The subconjunctival administration of FD006, bevacizumab or dexamethasone could significantly inhibit the growth of CoNV contrasting to N.S (p < 0.01). At the early stage, FD006 showed better inhibitory effect on the growth of CoNV compared with bevacizumab (p < 0.05). Western blot analysis showed that FD006 could inhibit the expression of VEGF, VEGFR-1, VEGFR-2, MMP-9 and ICAM-1, which could explain its favorable anti-angiogenic activity. CONCLUSIONS: The pharmacological characteristics of FD006 were similar or even a little better than bevacizumab in inhibiting corneal neovascularization.

Non-alcoholic fatty liver disease (NAFLD) fibrosis score predicts 6.6-year overall mortality of Chinese patients with NAFLD.

The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has emerged as a useful predictor of long-term outcome in NAFLD patients. We evaluated the predictive performance of the NFS for overall mortality in a Chinese population with NAFLD. All NAFLD patients diagnosed ultrasonographically at Xixi Hospital of Hangzhou between 1996 and 2011 were retrospectively recruited to the study. Outcome was determined by interview and causes of death were confirmed by medical records. The area under the receiver operating characteristic curve (AUCROC ) was used to determine the predictive accuracy of the NFS, BARD (body mass index, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, diabetes) score, FIB-4 index and the AST/platelet ratio index (APRI) for mortality. Data from a total of 180 eligible patients (median age 39 years; 96 men) were analysed, with 12 deaths over a median follow-up period of 6.6 years (range 0.5-14.8 years). Using Cox model analysis, the NFS as a continuous variable was identified as the only predictor for all-cause mortality (hazard ratio 2.743, 95% confidence interval (CI) 1.670-4.504). The NFS yielded the highest AUCROC of 0.828 (95% CI 0.728-0.928, P < 0.05), followed by the FIB-4 index, APRI and BARD score (AUCROC 0.806 (P < 0.05), 0.732 (P < 0.05) and 0.632, respectively). The data indicated that the NFS is a useful predictor of 6.6-year all-cause mortality for Chinese patients with NAFLD.

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.

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.

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.

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.

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.

[Clinical study of autoantibody spectrum against ovarian cancer associated antigens combined with CA(125) in detecting and monitoring ovarian cancer].

OBJECTIVE: To evaluate the clinical value of autoantibody spectrum against ovarian cancer associated antigens combine CA(125) in detecting and monitoring ovarian cancer. METHODS: Circulating IgG, IgM autoantibodies against ovarian cancer associated antigens which included TM4SF1, C1D, TIZ, OV-142, FXR1 and OV-189 were measured by indirect ELISA in serum from 126 patients with ovarian cancer (prior treatment), 42 patients with benign ovarian masses, 142 healthy women. Cut off value of IgG, IgM autoantibodies were determined by receive operating characteristic (ROC) curve. CA(125) was measured in serum by immunoradiometric assay (IRMA). We evaluated the clinical value of combining multiple autoantibodies (autoantibody spectrum), combining autoantibody spectrum with CA(125) by binary logistic regresion. The positive ratio of autoantibody spectrum in serum (prior and post treatment) of 24 synchronization patients with ovarian cancer was analyzed to evaluate the value in monitoring state of illness. RESULTS: Our data indicated that serum contains IgG, IgM autoantibodies against ovarian cancer associated antigens. The positive ratio of IgG autoantibodies in serum from ovarian cancer patients and cancer-free patients were 34.1% - 47.6% and 13.0% - 19.0%, respectively (P < 0.05). The positive ratio of IgM autoantibodies in serum from ovarian cancer patients and cancer-free patients were 39.7% - 53.2% and 12.0% - 33.2%, respectively (P < 0.05). The positive ratio of IgG autoantibodies against FXR1 and IgM autoantibodies against TIZ, FXR1 and OV-189 in early stage (I-II) ovarian cancer (55.3%, 63.8%, 61.7% and 66.0%) were significantly higher than those in advanced (III-IV) ovarian cancer (34.2%, 39.2%, 26.6%, 45.6%; all P < 0.05). Combining five autoantibodies (TM4SF1 IgG, TM4SF1 IgM, C1D IgG, FXR1 IgG and TIZ IgM) showed significantly improved sensitivity (75.4%, P < 0.05), lower specificity (78.3%, P < 0.05) and similar accuracy (77.1%, P > 0.05) in detecting ovarian cancer compared to those of CA(125) (61.1%, 88.0%, 77.1%). But the autoantibody spectrum showed significantly improved sensitivity in classifying early stage (76.6%), compared to those of CA(125) (51.1%, P < 0.05). Combining autoantibody spectrum with CA(125) showed significantly improved sensitivity (85.7%), specificity (90.8%)and accuracy (88.7%) in detecting ovarian cancer compared to those of autoantibody spectrum alone (all P < 0.05), while CA(125) (61.1%, P < 0.05; 88.0%, P > 0.05; 77.1%, P < 0.05). The positive ratio of combine the autoantibody spectrum with CA(125) was significantly lower in 24 post-treatment serum (42%) compared to the pairing prior treatment serum (88%, P < 0.05). CONCLUSION: Combining the autoantibody spectrum against ovarian cancer associated antigens with CA(125) can improve sensitivity, specificity and accuracy in detecting early ovarian cancer and may be used to monitoring state of illness.

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.

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.