Prediction of injury localization in preoperative patients with gastrointestinal perforation: a multiomics model analysis.

BACKGROUND: The location of gastrointestinal perforation is essential for severity evaluation and optimizing the treatment approach. We aimed to retrospectively analyze the clinical characteristics, laboratory parameters, and imaging features of patients with gastrointestinal perforation and construct a predictive model to distinguish the location of upper and lower gastrointestinal perforation. METHODS: A total of 367 patients with gastrointestinal perforation admitted to the department of emergency surgery in Fujian Medical University Union Hospital between March 2014 and December 2020 were collected. Patients were randomly divided into training set and test set in a ratio of 7:3 to establish and verify the prediction model by logistic regression. The receiver operating characteristic curve, calibration map, and clinical decision curve were used to evaluate the discrimination, calibration, and clinical applicability of the prediction model, respectively. The multiomics model was validated by stratification analysis in the prediction of severity and prognosis of patients with gastrointestinal perforation. RESULTS: The following variables were identified as independent predictors in lower gastrointestinal perforation: monocyte absolute value, mean platelet volume, albumin, fibrinogen, pain duration, rebound tenderness, free air in peritoneal cavity by univariate logistic regression analysis and stepwise regression analysis. The area under the receiver operating characteristic curve of the prediction model was 0.886 (95% confidence interval, 0.840-0.933). The calibration curve shows that the prediction accuracy and the calibration ability of the prediction model are effective. Meanwhile, the decision curve results show that the net benefits of the training and test sets are greater than those of the two extreme models as the threshold probability is 20-100%. The multiomics model score can be calculated via nomogram. The higher the stratification of risk score array, the higher the number of transferred patients who were admitted to the intensive care unit (P < 0.001). CONCLUSION: The developed multiomics model including monocyte absolute value, mean platelet volume, albumin, fibrinogen, pain duration, rebound tenderness, and free air in the peritoneal cavity has good discrimination and calibration. This model can assist surgeons in distinguishing between upper and lower gastrointestinal perforation and to assess the severity of the condition.

Comparison between Clinical Utility of CXCL-8 and Clinical Practice Tumor Markers for Colorectal Cancer Diagnosis.

Owing to the high incidence and mortality rates of colorectal cancer (CRC), novel biomarkers for CRC diagnosis are critically needed. Therefore, this study is aimed at exploring the clinical utility of serum C-X-C motif chemokine 8 (CXCL-8) for CRC diagnosis and progression compared to the routinely used biomarkers, carcinoembryonic antigen (CEA), and carbohydrate antigen-19-9 (CA19-9). This study included 227 patients with CRC, 110 patients with colorectal adenoma (CA), and 123 healthy participants, who were recruited from the Fujian Medical University Union Hospital from July 1, 2019 to October 31, 2020. Serum concentrations of CXCL-8, CEA, and CA19-9 were detected using enzyme-linked immunosorbent assay and chemiluminescent microparticle immunoassay. Clinicopathological features of patients with CRC were collected and analyzed. The diagnostic efficacy of CXCL-8, CEA, and CA19-9 for CRC was evaluated using receiver operating characteristic (ROC) curves. We found that the serum concentrations of CXCL-8, CEA, and CA19-9 were significantly higher in patients with CRC than those in patients with CA and healthy controls. The diagnostic sensitivity of CXCL-8 alone was higher than those of CEA and CA19-9 both and when combined; thus, CXCL-8 may be better at discriminating patients with CRC from healthy controls and patients with CA. Moreover, combining CXCL-8 with CEA or CA19-9 improved their respective diagnostic performances in distinguishing patients with CRC from CA patients and healthy participants. Notably, we also found that serum concentrations of CXCL-8 were positively correlated with metastases and tumor size. Therefore, our study suggests that serum CXCL-8 may serve as an improved biomarker for CRC diagnosis compared to the traditional tumor markers CEA and CA19-9. Moreover, our findings indicate the potential efficacy of serum CXCL-8 levels as a CRC prognostic biomarker.

Methylated Septin 9 as a Promising Biomarker in the Diagnosis and Recurrence Monitoring of Colorectal Cancer.

Purpose: The clinical utility of plasma methylated septin 9 (mSEPT9) DNA in screening and recurrence monitoring for colorectal cancer (CRC) is highly promising. The present study was performed to determine the diagnostic value of mSEPT9 in CRC detection and recurrence monitoring in Chinese patients. Methods: Overall, 616 patients newly diagnosed with CRC and 122 individuals with no evidence of disease were recruited from October 1, 2019, to May 31, 2021, at Fujian Medical University Union Hospital. Plasma and serum samples were collected for analyzing mSEPT9, carcinoembryonic antigen (CEA), and carbohydrate antigen-19-9 (CA19-9). Data on clinicopathological characteristics were collected and analyzed. Sensitivity and specificity were calculated to evaluate the diagnostic potential of each marker; the receiver operating characteristic (ROC) curve was applied for the assessment of diagnostic value, and comparisons among mSEPT9, CEA, CA19-9, and their combination were assessed via ROC curves. Results: mSEPT9 achieved an overall sensitivity and specificity of 72.94% and 81.97%, respectively, with an area under the curve (AUC) value of 0.826, which were higher than those of CEA (sensitivity: 43.96%; specificity: 96.72%; AUC: 0.789) and CA19-9 (sensitivity: 14.99%; specificity: 96.61%; AUC: 0.590). The combination of mSEPT9, CEA, and CA19-9 further improved sensitivity, specificity, and AUC value (sensitivity: 78.43%; specificity: 86.07%; AUC: 0.878), respectively. Notably, the mSEPT9 positivity rate was significantly associated with TNM stage, T stage, N stage, tumor size, vascular invasion, and nerve invasion among patients with CRC. A 100% correlation was observed between the positive results of the mSEPT9 test and recurrence or metastasis in patients after therapeutic intervention. Conclusion: Our findings suggest that mSEPT9 may represent a potential biomarker for the diagnosis and prognosis of CRC compared with CEA and CA19-9. Postoperative mSEPT9 status may represent the first noninvasive marker of CRC recurrence or metastasis.

Cyr61 mediates oxaliplatin resistance in colorectal cancer cells by regulating Bcl-xL expression.

Although the clinical application of oxaliplatin (L-OHP) has improved the survival of colorectal cancer (CRC) patients, approximately half of patients with CRC fail to achieve good clinical outcomes, indicating resistance to L-OHP therapy. Cysteine-rich protein 61 (Cyr61), a multifunctional extracellular matrix protein, is highly expressed in a variety of tumors; increased Cyr61 expression is known to be closely involved in the chemotherapeutic resistance of many tumors, but its role in the L-OHP resistance of CRC cells has not been studied. In this study, we aimed to investigate the role of Cyr61 in the L-OHP resistance of CRC cells and examine the underlying mechanism. Our findings showed that the mRNA and protein levels of Cyr61 in L-OHP-resistant cells were significantly increased compared with those in nonresistant cells. Knockdown of Cyr61 enhanced the chemosensitivity of L-OHP-resistant cells to L-OHP. Mechanistically, we found that overexpression of Cyr61 decreased L-OHP-induced apoptosis in drug-resistant CRC cells through the regulation of Bcl-xL. Collectively, our results revealed for the first time that Cyr61 plays a crucial role in the resistance of CRC cells to L-OHP and indicated that targeting Cyr61 may be a promising therapeutic strategy to overcome L-OHP resistance in CRC.

[Values of Hematological Indicators in the Screening of α-Thalassemia in Fujian Area of China].

OBJECTIVE: To analyze the genotypes and the hematological phenotypic characteristics of α-thalassemia in different areas of Fujian and to evaluate the values of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), hemoglobin (Hb), RBC distribution width/red blood cell (RDW/RBC) for screening α-thalassemia in this area. METHODS: The Gap-PCR assay was applied for detecting 3 common deletional mutations of patients with α-thalassemia, and the reverse dot-blot (RDB) assay was adopted to detect the foci of 3 common non-deletional gene mutations.Then,the hematological parameters of individuals with α-thalassemia were analyzed. Finally, the optimal cut-off value in hematological indexes for screening α-thalassemia were determined by the ROC curve. RESULTS: Altogether 16 types of gene mutations were found in 772 patients with α-thalassemia. Among them, the -SEA/αα deletion mutation was the most common which was observed in 521 cases(67.49%). Compared with the control group, the differences in MCV, MCH, and Hb were statistically significant between the patients of the same sex but no same type. In male groups, the RDW/RBC ratio was statistically significant in individuals of light type and HbH disease as compared with the healthy control group. But in female groups, the statistical different of RDW/RBC ratio was found between only HbH disease group and control group. MCV<81.25 fl, MCH<27.30 pg, Hb(male)<128.5 g/L, and Hb(female) <123.5 g/L, with the highest specificity and the highest sensitivity, were the best cut-off points for screening α-thalassemia in the laboratory. CONCLUSION: Due to the difference of regional heterogeneity and hospital equipment environment, the different laboratories need to establish cut-off value for screening α-thalassemia suitable for its local region. In future, our laboratory can use MCV<81.25 fl, MCH<27.30 pg, Hb(male)<128.5 g/L, and Hb(female) <123.5 g/L for value for clinical screening, of α-thalassemia.

Cyr61 decreases Cytarabine chemosensitivity in acute lymphoblastic leukemia cells via NF-κB pathway activation.

Elevated Cyr61 levels have been reported in various malignancies. Elevation of Cyr61 protein levels contributes to the proliferation, metastasis, and chemotherapy resistance of malignant cells. Previously, it was discovered that Cyr61 is elevated in both the plasma and the bone marrow supernatants of patients with acute lymphoblastic leukemia (ALL), promoting ALL cell survival. However, the role of Cyr61 in the chemotherapeutic resistance of ALL cells remains unknown. The aim of the current study was to investigate the role of Cyr61 in regulating ALL cell chemosensitivity to Ara­C. It was found that Cyr61 is overexpressed in bone marrow mononuclear cells from patients with ALL. Increased Cyr61 effectively decreased Ara­C­induced apoptosis of ALL cells, and its function was blocked by the use of the anti­Cyr61 monoclonal antibody 093G9. Furthermore, Cyr61 increased the level of Bcl­2 in Ara­C­treated ALL cells. Mechanistically, it was shown that Cyr61 affected ALL cell resistance to Ara­C partially via the NF­κB pathway. Taken together, the present study is the first, to the best of our knowledge, to reveal that Cyr61 is involved in ALL cell resistance through the NF­κB pathway. The findings support a functional role for Cyr61 in promoting chemotherapy resistance, suggesting that targeting Cyr61 directly or its relevant effector pathways may improve the clinical responses of patients with ALL.

Evaluation of platelet indices as diagnostic biomarkers for colorectal cancer.

Altered platelet indices, including platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT), have been found in various cancer types. This study aimed to evaluate the role of platelet indices as potential biomarkers for the diagnosis of colorectal cancer (CRC), and to assess the association between platelet indices and CRC clinicopathological characteristics. The study included 783 subjects with CRC, 463 subjects with colorectal adenomas (CA), and 689 control subjects from June 2015 to October 2017. All participants' clinicopathological characteristics were collected and analyzed. Here, we found that PC, MPV and PCT levels in CRC patients were significantly higher than those in CA patients and healthy participants (p < 0.001); however, PDW level in CRC patients was significantly higher than that in healthy participants while lower than that in CA patients. Receiver-operating characteristic (ROC) analysis indicated that combined detection of PCT and CEA appears to be a more effective marker to distinguish CRC patients from CA patients, with 70% sensitivity and 83% specificity. Among CRC patients, PC and PCT levels were associated with TNM stages and tumor size; MPV and PCT levels were associated with vascular invasion. Our findings suggest that altered PC, MPV and PCT levels might serve as potential biomarkers for the diagnosis and prognosis of CRC.

Clinical Usefulness and Prognostic Value of Red Cell Distribution Width in Colorectal Cancer.

Red blood cell distribution width (RDW) indicates the heterogeneity in the size of circulating red blood cells. Increasing studies showed that RDW may be a diagnostic and prognostic marker in various tumors. To investigate the value of RDW as a biomarker in the diagnosis and prognosis of colorectal cancer (CRC), we evaluated 783 newly diagnosed CRC patients, 463 colorectal adenomas (CA) patients, and 331 healthy controls from June 2015 to October 2017 at Fujian Medical University Union Hospital. We found that RDW levels were significantly higher in CRC groups compared with both the CA and healthy control groups (P<0.001). Receiver-operating characteristic (ROC) analysis showed that the area under the ROC curve (AUC) for RDW, CEA, and CA19-9 was 0.643, 0.742, and 0.629 in discriminating CRC patients from healthy controls, respectively. When RDW cut-off value of 13.95 was applied, we distinguished CRC patients from healthy controls with a sensitivity of 41% and a specificity of 94%. Moreover, combined detection of RDW, CEA, and CA19-9 appeared to be a better diagnostic performance with a sensitivity of 56% and a specificity of 99%. However, RDW had little diagnostic value in the differential diagnosis between CRC patients and CA patients. More importantly, RDW levels were significantly associated with TNM stage, pT stage, pM stage, and tumor size among CRC patients. Overall, our study suggested that RDW might be an auxiliary biomarker for diagnosis and prognosis of CRC.

Epidemiology of Humanpapilloma virus infection among women in Fujian, China.

BACKGROUND: Human papillomavirus (HPV) infection is the main etiological factor for the development of cervical cancer. Here we assessed the prevalence and distribution of HPV genotypes in Fujian population. METHODS: A total of 8678 women aging from 17 to 84 years olds were recruited from the Fujian Medical University Union Hospital in Fujian Province. Every woman had a face-to-face interview. Cervical samples were collected from each participant and HPV screening was conducted using microarray hybridization. RESULTS: Our study showed that the HPV prevalence in Fujian province was 38.3%. Among the positive individuals, 70.6% were detected for single HPV infection, 29.4% for multiple HPV infections. Further analysis showed that the prevalence of HPV infection significantly increased from 2009 to 2015. The four most common high risk human papillomavirus (HR-HPV) genotypes were HPV16 (8.5%), HPV52 (7.9%), HPV58 (6.2%), HPV 53 (3.5%), collectively accounting for 60.5% of all detected HPV infection. Age subgroup analysis showed two peaks for the frequencies of overall and multiple HPV infections, one for the group of women under 25 years old, and the other for the group over 55 years old. CONCLUSIONS: HPV infection is becoming serious in Fujian province, which indicates the imperative to implement a HPV vaccination and screening program for this region.

Cyr61 participates in the pathogenesis of acute lymphoblastic leukemia by enhancing cellular survival via the AKT/NF-κB signaling pathway.

Cyr61 (CCN1) is the product of a growth factor-inducible immediate early gene and is involved in cell adhesion, survival, proliferation, and differentiation. Cyr61 is overexpressed in human tumors and is involved in the development of tumors. However, the role that Cyr61 plays in acute lymphoblastic leukemia (ALL) cells remains undetermined. The aim of this study was to identify the role of Cyr61 in regulating ALL cell survival. Here, we found that the level of Cyr61 was increased in the plasma and bone marrow (BM) from ALL patients compared with samples from normal control patients. Furthermore, we observed that Cyr61 could effectively stimulate Jurkat (T ALL cell lines), Nalm-6 (B ALL cell lines), and primary ALL cell survival. Mechanistically, we showed that Cyr61 stimulated ALL cell survival via the AKT/NF-κB signaling pathways and the consequent up-regulation of Bcl-2. Taken together, our study is the first to reveal that Cyr61 is elevated in ALL and promotes cell survival through the AKT/NF-κB pathway by up-regulating Bcl-2. Our findings suggest that Cyr61 plays an important role in the pathogenesis of ALL.

Mature dendritic cells cause Th17/Treg imbalance by secreting TGF-ß1 and IL-6 in the pathogenesis of experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is generally acknowledged to be an autoimmune disease, but its etiology remains unknown. The most intensively studied animal model of MS is experimental autoimmune encephalomyelitis (EAE). Dendritic cells (DCs), the professional antigen presenting cells (APCs), have gained increasing attention because they connect innate and adaptive immunity. The aim of this study was to determine the role of mature DCs in the pathogenesis of EAE. It was found that the number of mature DCs in the EAE spleen increased compared to the control group (p < 0.05). And there was an imbalance between Th17 (effector) and Treg (regulatory) in EAE. The data showed that mature DCs can regulate the differentiation of Th17 and Treg in EAE. In addition, there was a significant difference in secretion of TGF-ß1 and IL-6 between mature DCs from mice with EAE and controls. The present data suggest that mature DCs cause an imbalance between Th17 and Treg by secreting TGF-ß1 and IL-6 in the pathogenesis of EAE disease. Thus, targeting DC may be an effective strategy for treating MS.

[Th17/Treg unbalance is involved in the pathogenesis of experimental autoimmune encephalomyelitis].

OBJECTIVE: To investigate the role of Th17/Treg unbalance in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). METHODS: EAE was modeled in mice and the number of regulatory T cells (Tregs) in spleen of EAE mice was detected by flow cytometry. The expressions of Foxp3 and RoR-γt mRNA in the spleen of EAE mice and IL-17 mRNA in the brain of EAE mice were evaluated by real-time quantitative PCR and the levels of IL-6, TGF-ß and IL-17 in the serum of EAE mice were examined by ELISA. RESULTS: Compared with control group, the number of CD4(+)CD25(+) Foxp3(+) Tregs and the expression of Foxp3 mRNA in the spleen of EAE mice dramatically decreased in the early and peak stage of EAE (P<0.05), but increased in chronic stage of EAE (P<0.05); the RoR-γt mRNA expression from mouse spleen at the early stage of EAE was significant raised (P<0.05), but was not significantly different at the peak and chronic stage of EAE from that in control group (P>0.05). The levels of IL-6 and TGF-ß in the serum of EAE group dramatically increased compared with control group (P<0.05). With the development of EAE, the level of IL-6 gradually decreased, and there was no statistical difference in the chronic stage of EAE compared with control group (P>0.05). However, the level of TGF-ß was higher than that in control group in the chronic stage of EAE (P<0.05). Compared with those in control group, the concentration of IL-17A and the expression of IL-17 mRNA dramatically increased in different stages of EAE group, especially in peak stage (P<0.05). CONCLUSION: Th17/Treg unbalance may be involved in the pathogenesis of EAE.