Identification of core carcinogenic elements based on the age-standardized mortality rate of lung cancer in Xuanwei Formation coal in China.

In this study, the core carcinogenic elements in Xuanwei Formation coal were identified. Thirty-one samples were collected based on the age-standardized mortality rate (ASMR) of lung cancer; Si, V, Cr, Co, Ni, As, Mo, Cd, Sb, Pb, and rare earth elements and yttrium (REYs) were analyzed and compared; multivariate statistical analyses (CA, PCA, and FDA) were performed; and comprehensive identification was carried out by combining multivariate statistical analyses with toxicology and mineralogy. The final results indicated that (1) the high-concentration Si, Ni, V, Cr, Co, and Cd in coal may have some potential carcinogenic risk. (2) The concentrations of Cr, Ni, As, Mo, Cd, and Pb meet the zoning characteristics of the ASMR, while the Si concentration is not completely consistent. (3) The REY distribution pattern in Longtan Formation coal is lower than that in Xuanwei Formation coal, indicating that the materials of these elements in coal are different. (5) The heatmap divides the sampling sites into two clusters and subtypes in accordance with carcinogenic zoning based on the ASMR. (6) PC1, PC2, and PC3 explain 62.629% of the total variance, identifying Co, Ni, As, Cd, Mo, Cr, and V. (7) Fisher discriminant analysis identifies Ni, Si, Cd, As, and Co based on the discriminant function. (8) Comprehensive identification reveals that Ni is the primary carcinogenic element, followed by Co, Cd, and Si in combination with toxicology. (9) The paragenesis of Si (nanoquartz), Ni, Co, and Cd is an interesting finding. In other words, carcinogenic elements Ni, Co, Cd, and Si and their paragenetic properties should receive more attention.

Associations between coagulation factors and livedoid vasculopathy and the efficacy and safety of rivaroxaban in patients with livedoid vasculopathy: a retrospective study.

BACKGROUND: The mechanism of livedoid vasculopathy (LV) remains unknown. OBJECTIVE: To investigate the association between coagulation factors and LV and to assess the efficacy and safety of rivaroxaban in the treatment of patients with LV. METHODS: From May 2019 to July 2022, 89 LV patients and 35 healthy controls were included in the cross-sectional cohort to measure the levels of coagulation factors. In addition, 55 LV patients treated with rivaroxaban were included in the treatment cohort to assess the complete remission rate of ulcers (n=44) and retiform purpura (n=11) within 12 weeks. RESULTS: In the cross-sectional cohort, the activities of coagulation factor X in LV patients were significantly higher than healthy controls (median [IQR]: 110.5% [97.5-127.0%] vs 101.3% [91.6-115.6%]; P=0.047). In addition, the coagulation factor X activities in the progressive stage were higher than in the stable stage (median [IQR]: 111.6% [102.3-132.5%] vs 105.4% [92.9-118.8%]; P=0.037). Moreover, the coagulation factor X activities were higher in the progressive stage than in the stable stage in the paired LV patients (P=0.035). In the treatment cohort of rivaroxaban, 90.9% (40/44) of patients with ulcers achieved complete remission within 12 weeks, and 72.7% (8/11) of patients with retiform purpura achieved complete remission within 12 weeks. Mild side effects occurred in 25.5% of patients, including menorrhagia (n=10), gingival bleeding (n=3), and hemorrhage (n=1). CONCLUSIONS: It was demonstrated that coagulation factor X was associated with the incidence and severity of LV. In addition, rivaroxaban was an effective and safe treatment for ulcers and retiform purpura of LV.

Health-related quality of life and associated factors among non-melanoma skin cancer patients: a cross-sectional study.

Background: Non-melanoma skin cancer (NMSC) is a common malignant tumor that can lead to disability and a high recurrence rate, thus affecting the health-related quality of life (HRQoL) of patients. However, the HRQoL and its associated factors among Chinese patients with NMSC remain unknown. Considering HRQoL is a comprehensive indicator to assess an individual's health and well-being, as well as to provide a basis for future treatment decisions and care interventions, we investigated Chinese NMSC patients to assess the status of HRQoL, and to explore the associated factors of HRQoL. Methods: This cross-sectional study was conducted at the largest dermatology hospital in China from November 2017 to February 2022. Participants were over 18 years, diagnosed with NMSC by pathological examination, and able to provide informed consent. A consecutive sampling technique was used and 202 eligible patients with NMSC were surveyed. Dermatology Life Quality Index, general information questionnaire, Athens Insomnia Scale, and Self-rating Anxiety Scale were used to measure their HRQoL and relevant information. Descriptive statistics, non-parametric test and Spearman's correlation analyses were used to compare the differences and assess the relationships between participants' demographic and clinical factors, sleep, anxiety, and HRQoL. Multiple linear regression analysis was performed to identify factors associated with HRQoL. Results: A total of 176 NMSC patients (mean age 66 years, including 83 males and 93 females) were included. The median score of HRQoL was 3 [1, 7], and 116 (65.9%) NMSC patients' HRQoL was negatively affected. The score of the symptom and feeling domain was the highest 2 [1, 3], NMSC patients with squamous cell carcinoma and extramammary Paget disease had a significantly lower HRQoL than patients with basal cell carcinoma (P<0.05). Primary skin diseases, long-term history of mechanical stimulation, poor sleep, and anxiety were the associated factors of the HRQoL, comprising 43.5% of the total variance. Conclusions: Most patients with NMSC live with poor HRQoL in China. It is necessary to provide timely assessment and develop targeted strategies to improve NMSC patients' HRQoL, such as multiple forms of health education, psychological care for the target population, and effective measures to improve patients' sleep.

N6-methyladenosine reader YTHDF3 regulates melanoma metastasis via its 'executor'LOXL3.

BACKGROUND: A number of studies have demonstrated that N6-methyladenosine (m6A) plays a vital role in the pathological process of various tumours. Recently, it was found that m6A writers or erasers affect the tumourigenesis of melanoma. However, the relationship between m6A readers such as YTH domain family (YTHDF) proteins and melanoma was still elusive. METHODS: RT-qPCR, Western blot and immunohistochemistry were conducted to measure the expression level of YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) and lysyl oxidase-like 3 (LOXL3) in melanoma tissues and cells. The effects of YTHDF3 and LOXL3 on melanoma were verified in vitro and in vivo. Multi-omics analysis including RNA-seq, MeRIP-seq, RIP-seq and mass spectrometry analyses was performed to identify the target. The interaction between YTHDF3 and LOXL3 was verified by RT-PCR, Western blot, MeRIP-qPCR, RIP-qPCR and CRISPR-Cas13b-based epitranscriptome engineering. RESULTS: In this study, we found that m6A reader YTHDF3 could affect the metastasis of melanoma both in vitro and in vivo. The downstream targets of YTHDF3, such as LOXL3, phosphodiesterase 3A (PDE3A) and chromodomain helicase DNA-binding protein 7 (CHD7) were identified by means of RNA-seq, MeRIP-seq, RIP-seq and mass spectrometry analyses. Besides, RT-qPCR, Western blot, RIP-qPCR and MeRIP-qPCR were performed for subsequent validation. Among various targets of YTHDF3, LOXL3 was found to be the optimal target of YTHDF3. With the application of CRISPR-Cas13b-based epitranscriptome engineering, we further confirmed that the transcript of LOXL3 was captured and regulated by YTHDF3 via m6A binding sites. YTHDF3 augmented the protein expression of LOXL3 without affecting its mRNA level via the enrichment of eukaryotic translation initiation factor 3 subunit A (eIF3A) on the transcript of LOXL3. LOXL3 downregulation inhibited the metastatic ability of melanoma cells, and overexpression of LOXL3 ameliorated the inhibition of melanoma metastasis caused by YTHDF3 downregulation. CONCLUSIONS: The YTHDF3-LOXL3 axis could serve as a promising target to be interfered with to inhibit the metastasis of melanoma.

Anomalous Connection of the Left Pulmonary Vein to the Coronary Sinus with Intact Atrial Septum in a Young Woman.

BACKGROUND: Left-sided partial anomalous pulmonary venous connection (PAPVC) is a rare congenital abnormal cardiac defect. An intact atrial septum is more uncommon. As we know, a connection of the left pulmonary vein (LPV) to the coronary sinus (CS) with an intact atrial septum has not been previously reported. CASE REPORT: We report an 18-year-old woman with this rare anomaly. She showed no obvious clinical symptoms. An echocardiogram revealed the primary diagnosis, and this diagnosis was confirmed during the operation. This patient underwent a successful surgical repair. Artificial atrial septal defect (ASD) and coronary sinus orifice were inserted into the left atrium by patch. The patient recovered smoothly without complications after the operation. CONCLUSION: Given the high risk of developing congestive heart failure, we advocate for intervention at the preschool age. Surgical techniques depend on the number and location of abnormal veins or veins.

Influence of verapamil on pressure overload-induced ventricular arrhythmias by regulating gene-expression profiles.

BACKGROUND: Life-threatening ventricular arrhythmias can lead to sudden cardiac death in patients. This study aimed to investigate the changes in gene profiles involved when verapamil (VRP) affects increased wall stress (pressure overload)-induced ventricular arrhythmias, thus revealing the potential causative molecular mechanisms and therapeutic targets through gene-expression identification and functional analysis. METHODS: Animal models with wall stress-induced ventricular arrhythmias were established. Low (0.5 mg/kg) and high (1 mg/kg) doses of VRP were administered intravenously 10 minutes before transverse aortic constriction, and average ventricular arrhythmia scores were calculated. Next, we evaluated the molecular role of VRP by characterising differential gene-expression profiles between VRP-pretreated (1 mg/kg) and control groups using RNA-sequencing technology. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to reveal molecular function. A protein-protein interaction (PPI) network was then developed. RESULTS: VRP exerted its anti-arrhythmic effects in response to increases in left ventricular (LV) afterload. We detected differentially expressed genes (DEGs), of which 36 were upregulated and 1 397 downregulated, between the VRP-pretreated and model groups during acute increases in LV wall stress. GO analysis demonstrated that the DEGs were associated with cytoskeletal protein binding. KEGG analysis showed that enriched pathways were mainly distributed in adherens junctions, actin cytoskeleton regulation and the MAPK signalling pathway. Centralities analysis of the PPI identified Rac1, Grb2, Rbm8a and Mapk1 as hub genes. CONCLUSIONS: VRP prevented acute pressure overload-induced ventricular arrhythmias, possibly through the hub genes Rac1, Grb2, Rbm8a and Mapk1 as potential targets of VRP.

BCL-2 expression promotes immunosuppression in chronic lymphocytic leukemia by enhancing regulatory T cell differentiation and cytotoxic T cell exhaustion.

BACKGROUND: Chronic lymphocytic leukemia (CLL) results in increased susceptibility to infections. T cell dysfunction is not associated with CLL in all patients; therefore, it is important to identify CLL patients with T cell defects. The role of B-cell lymphoma-2 (BCL-2) in CLL has been explored; however, few studies have examined its role in T cells in CLL patients. Herein, we have investigated the regulatory role of BCL-2 in T cells in the CLL tumor microenvironment. METHODS: The expression of BCL-2 in T cells was evaluated using flow cytometry. The regulatory roles of BCL-2 were investigated using single-cell RNA sequencing (scRNA-seq) and verified using multi-parameter flow cytometry on CD4 and CD8 T cells. The clinical features of BCL-2 expression in T cells in CLL were also explored. RESULTS: We found a significant increase in BCL-2 expression in the T cells of CLL patients (n = 266). Single cell RNA sequencing (scRNA-seq) indicated that BCL-2+CD4+ T cells had the gene signature of increased regulatory T cells (Treg); BCL-2+CD8+ T cells showed the gene signature of exhausted cytotoxic T lymphocytes (CTL); and increased expression of BCL-2 was associated with T cell activation and cellular adhesion. The results from scRNA-seq were verified in peripheral T cells from 70 patients with CLL, wherein BCL-2+CD4+ T cells were enriched with Tregs and had higher expression of interleukin-10 and transforming growth factor-ß than BCL-2-CD4+ T cells. BCL-2 expression in CD8+T cells was associated with exhausted cells (PD-1+Tim-3+) and weak expression of granzyme B and perforin. T cell-associated cytokine profiling revealed a negative association between BCL-2+ T cells and T cell activation. Decreased frequencies and recovery functions of BCL-2+T cells were observed in CLL patients in complete remission after treatment with venetoclax. CONCLUSION: BCL-2 expression in the T cells of CLL patients is associated with immunosuppression via promotion of Treg abundance and CTL exhaustion.

A Rare Reason of Cardiogenic Shock and Acute Myocardial Infarction: Aortic Valve Myxoma.

Aortic valve myxoma is a rare benign cardiac neoplasm. The association of aortic valve myxoma with cardiogenic shock and acute myocardial infarction has been reported in few observations. We report the case of a 19-year-old male patient, who underwent chest pain for two weeks, then further examinations indicated a soft spherical mass on the left coronary cusp. The patient had sporadic cardiogenic shock and acute myocardial infarction during the preoperative preparation, and we carried out emergency effective cardiopulmonary resuscitation (CPR), followed by emergency surgical operation for aortic valve tumor. Postoperative pathology showed it was a myxoma. The patient recovered smoothly and was discharged on postoperative day 7. Cardiogenic shock and acute myocardial infarction are very nonspecific, and we should be aware that patients with cardiogenic shock and acute myocardial infarction possibly suffer from aortic valve myxoma.

Effects of L-carnitine combined with pancreatic kininogenase on thioredoxin 2, thioredoxin reductase 1, and sperm quality in patients with oligoasthenospermia.

BACKGROUND: To study the effects of L-carnitine (LC) combined with pancreatic kininogenase on thioredoxin 2 (Trx 2), thioredoxin reductase 1 (TrxR 1), and sperm quality in patients with oligoasthenospermia. METHODS: A total of 300 male infertility patients with oligoasthenospermia who were treated in the andrology clinic of our hospital from December 2019 to December 2020 were randomly divided into an LC group and combined treatment group, and 50 males with normal semen were selected as a control group. The computer-assisted semen analysis system (CASA) was used to detect the total number, vitality, and forward motility of the sperm before and after treatment, and sperm morphology was detected by the Diff-Quik method of the sperm staining kit. Sperm chromatin dispersion (SCD) method was used to detect sperm DNA fragments, and Western-blot was used to detect the protein expression of Trx 2 and TrxR 1. RESULTS: There were no significant differences in sperm density, motility rate, forward motile sperm rate, and DNA fragmentation rate in oligoasthenospermia patients before treatment (P>0.05). However, after 1 month of treatment, the sperm density, motility rate, and forward motile sperm rate were all higher than before treatment (P<0.05), while the DNA fragmentation rate was lower than before treatment. At the same time, each index of semen in the combination group was higher than that in the LC group (P<0.05), and the total effective rate in the combination group was significantly higher than in the LC group (P<0.01). The expression of Trx2 protein in oligoasthenospermia patients was significantly increased (P<0.05), while the expression of TrxR1 protein was significantly decreased (P<0.05). After 3 months of treatment, the expression of Trx2 protein was significantly decreased (P<0.05), while the expression of TrxR1 protein was significantly increased (P<0.05). CONCLUSIONS: The results suggest Trx 2 and TrxR 1 may be candidate protein markers for oligoasthenospermia. LC combined with pancreatic kininogenase in the treatment of male oligoasthenospermia can effectively promote sperm maturation, enhance sperm motility, and improve semen quality, which has high application value.

MiRNA-339 targets and regulates ZNF689 to inhibit the proliferation and invasion of gastric cancer cells.

BACKGROUND: Gastric cancer (GC) is the most common malignant tumor of the digestive system, and its mortality rate ranks first among malignant tumors. However, the pathogenesis of GC has not yet been fully elucidated. This study found that microRNA (miRNA)-339 is abnormally expressed in GC tissues. However, the role and molecular mechanism of miRNA-339 in the occurrence and development of GC are still unclear. METHODS: Fluorescence quantitative polymerase chain reaction (qPCR) was used to detect the expression level of miRNA-339 in GC tissues and adjacent tissues and analyze the correlation with the clinicopathological characteristics of GC patients. Cell counting kit-8 (CCK-8) and Transwell experiments detected the effect of overexpression of miRNA-339 on the proliferation, invasion, and migration of GC cells. The luciferase reporter gene detected the downstream target molecules regulated by miRNA-339, and western blot was employed to detect the effect of overexpression of miRNA-339 on the expression of ZNF689. RESULTS: The results of fluorescence qPCR showed that miRNA-339 was less expressed in GC tissues compared with adjacent tissues, and it was correlated with the patient's clinical tumor, node, metastasis (TNM) grade and lymph node metastasis. Cell function experiments showed that overexpression of miRNA-339 can significantly inhibit the proliferation, invasion, and migration of GC cells. The luciferase reporter gene showed that miRNA-339 can bind to the 3'-UTR region of ZNF689, and overexpression of miRNA-339 can significantly inhibit the expression of ZNF689 in GC cells. Overexpression of ZNF689 can significantly block the ability of overexpression of miRNA-339 to inhibit the proliferation and migration of GC cells. CONCLUSIONS: miRNA-339 inhibits the proliferation and invasion of GC cells through targeted regulation of the expression of ZNF689. In addition, the expression level of miRNA-339 can be used as a biomarker for the prognosis of GC.

Dissecting molecular mechanisms underlying H2O2-induced apoptosis of mouse bone marrow mesenchymal stem cell: role of Mst1 inhibition.

BACKGROUND: Bone marrow mesenchymal stem cell (BM-MSC) has been shown to treat pulmonary arterial hypertension (PAH). However, excessive reactive oxygen species (ROS) increases the apoptosis of BM-MSCs, leading to poor survival and engraft efficiency. Thus, improving the ability of BM-MSCs to scavenge ROS may considerably enhance the effectiveness of transplantation therapy. Mammalian Ste20-like kinase 1 (Mst1) is a pro-apoptotic molecule which increases ROS production. The aim of this study is to uncover the underlying mechanisms the effect of Mst1 inhibition on the tolerance of BM-MSCs under H2O2 condition. METHODS: Mst1 expression in BM-MSCs was inhibited via transfection with adenoviruses expressing a short hairpin (sh) RNA directed against Mst1 (Ad-sh-Mst1) and exposure to H2O2. Cell viability was detected by Cell Counting Kit 8 (CCK-8) assay, and cell apoptosis was analyzed by Annexin V-FITC/PI, Caspase 3 Activity Assay kits, and pro caspase 3 expression. ROS level was evaluated by the ROS probe DCFH-DA, mitochondrial membrane potential (ΔΨm) assay, SOD1/2, CAT, and GPx expression. Autophagy was assessed using transmission electron microscopy, stubRFP-sensGFP-LC3 lentivirus, and autophagy-related protein expression. The autophagy/Keap1/Nrf2 signal in H2O2-treated BM-MSC/sh-Mst1 was also measured. RESULTS: Mst1 inhibition reduced ROS production; increased antioxidant enzyme SOD1/2, CAT, and GPx expression; maintained ΔΨm; and alleviated cell apoptosis in H2O2-treated BM-MSCs. In addition, this phenomenon was closely correlated with the autophagy/Keap1/Nrf2 signal pathway. Moreover, the antioxidant pathway Keap1/Nrf2 was also blocked when autophagy was inhibited by the autophagy inhibitor 3-MA. However, Keap1 or Nrf2 knockout via siRNA had no effect on autophagy activation or suppression. CONCLUSION: Mst1 inhibition mediated the cytoprotective action of mBM-MSCs against H2O2-induced oxidative stress injury. The underlying mechanisms involve autophagy activation and the Keap1/Nrf2 signal pathway.

Implementation of the plasma MYCN/NAGK ratio to detect MYCN amplification in patients with neuroblastoma.

Detection of amplification of the MYCN gene is essential for determining optimal treatment and estimating prognosis of patients with neuroblastoma (NB). DNA FISH with neuroblastoma tissues or patient-derived bone marrow cells is the standard clinical practice for the detection of MYCN amplification. As tumor cells may often be unavailable, we developed a method to detect MYCN amplification in the plasma of patients with neuroblastoma. Taking single-copy NAGK DNA as reference, we used real-time quantitative PCR (qPCR) to determine the MYCN/NAGK ratio in the plasma of 115 patients diagnosed with NB. An increased MYCN/NAGK ratio in the plasma was consistent with MYCN amplification as assessed by DNA FISH. The AUC for a MYCN/NAGK ratio equal to 6.965 was 0.943, with 86% sensitivity and 100% specificity. Beyond the threshold of 6.965, the MYCN/NAGK ratio correlated with a heavier tumor burden. Event-free and overall survival of two years were significantly shortened in stage 4 patients with a MYCN/NAGK ratio higher than 6.965. Plasma MYCN/NAGK ratios increased in patients with progressive disease and relapse. Thus, we conclude that the determination of the plasma MYCN/NAGK ratio by qPCR is a noninvasive and reproducible method to measure MYCN amplification in patients with NB.

Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma.

BACKGROUND: Neuroblastoma is the most common extracranial solid tumor of childhood. The high rate of recurrence is associated with a low survival rate for patients with high-risk neuroblastoma. There is thus an urgent need to identify effective predictive biomarkers of disease recurrence. METHODS: A total of 116 patients with high-risk neuroblastoma were recruited at Beijing Children's Hospital between February 2015 and December 2017. All patients received multidisciplinary treatment, were evaluated for the therapeutic response, and then initiated on maintenance treatment. Blood samples were collected at the beginning of maintenance treatment, every 3 months thereafter, and at the time of disease recurrence. Plasma levels of cell-free DNA (cfDNA) were quantified by qPCR. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of plasma cfDNA concentration to predict recurrence. RESULTS: Of the 116 patients, 36 (31.0%) developed recurrence during maintenance treatment. The median time to recurrence was 19.00, 9.00, and 8.00 months for patients who had achieved complete response (n = 6), partial response (n = 25), and stable disease (n = 5), respectively, after multidisciplinary treatment. The median plasma cfDNA concentration at the time of recurrence was significantly higher than the concentration in recurrence-free patients throughout maintenance treatment (29.34 ng/mL vs 10.32 ng/mL). Patients recorded a plasma cfDNA level ≥ 29 ng/mL an average of 0.55 months before diagnosis of disease recurrence. ROC analysis of the power of plasma cfDNA to distinguish between patients with or without recurrence yielded an area under the curve of 0.825, with optimal sensitivity and specificity of 80.6 and 71.3%, respectively, at a cfDNA level of 12.93 ng/mL. CONCLUSIONS: High plasma cfDNA concentration is a potential molecular marker to signal disease recurrence in patients with high-risk neuroblastoma.

Clinical significance of cell-free DNA concentration and integrity in serum of gastric cancer patients before and after surgery.

Early onset of gastric cancer (GC) is almost asymptomatic, thereby making early diagnosis and early treatment difficult. Blood samples were taken from 90 GC patients who had not undergone surgery, and from another set of 110 GC patients who had undergone surgery. The control consisted of 90 healthy individuals. Cell-free DNA (cfDNA) and its integrity were assayed using qPCR. The association between cfDNA levels and clinical presentations of GC was analyzed. In addition, cfDNA, carcino-embryonic antigen (CEA), carbohydrate antigen 724 (CA724), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) were subjected to specificity and sensitivity analyses using ROC. The levels of cfDNA of GC patients before surgery were markedly higher than corresponding values in patients with GC after surgery. Post-surgery, the two indices were also significantly higher in GC patients than in the healthy group. The correlation between cfDNA concentration/integrity and gender, age, TNM stage, tumor differentiation, tumor location, neuronspecific enolase (NSE), or alpha fetoprotein (AFP) expression, was not significant in GC patients before or after surgery. However, the correlation between cfDNA and concentrations of CEA/CA125 was significant. The CA199 expression level was significantly correlated with cfDNA integrity. The AUC values of cfDNA concentration and integrity were higher than other tumor markers. Measurement of cfDNA concentration and integrity may be an ideal tumor screening method with higher sensitivity and specificity than traditional tumor biomarkers. The cfDNA concentration and integrity are significantly increased in plasma of GC patients, and may serve as promising indicators for GC.

The significance of CO2 combining power in predicting prognosis of patients with stage II and III colorectal cancer.

Aim: This study was to evaluate whether CO2CP level in venous blood could predict prognosis of patients with colorectal cancer (CRC). Materials & methods: A retrospective cohort of 238 patients with CRC who received surgical resection and 176 CRC Stage IV patients were included. A total of 114 healthy people were recruited as control. CO2CP levels were obtained from medical records. Survival analysis was performed to evaluate CO2CP predictive potential. The patients were divided into CO2CP high or low group based on CO2CP optimal cut-off values. Conclusion: The decreased CO2CP in CRC patients was associated with advanced clinical stage, and suggested that decreased CO2CP may predict the worse outcomes of disease-free survival in II/III stage CRC patients.

Dynamic alterations of plasma cell free DNA in response to chemotherapy in children with neuroblastoma.

BACKGROUND: To improve cure rates for neuroblastoma (NB), it is important and necessary to evaluate therapy response. Our investigation focuses on using plasma cell free DNA (cfDNA) as a biomarker to determine tumor burden and minimal residual disease (MRD) of NB patients during chemotherapy. METHODS: Total 58 NB patients were recruited from July 2016 to December 2017. Therapy regime and risk classification were based on COG standard and BCH-NB-2007 protocol. RECIST study was used to judge response to therapy at the end of fourth cycle of chemotherapy (CC4) and maintenance stage (MS) respectively. Serial quantifications of cfDNA, NSE, and LDH were examined at four stages, including newly diagnosed, second and CC4, and maintenance. RESULTS: During early chemotherapy, 65.5% of NB kids responded well. Consistently, cfDNA, NSE, and LDH levels were down-regulated in NB patients with partial remission (PR) compared to those with stable disease (SD). In both training and predicting sets, the levels of cfDNA were significantly comparable between PR and SD only at CC4 stage. To predict the insufficient response to early chemotherapy, the optimal AUC value of cfDNA was 0.732 and 0.747 in training and predicting sets respectively, with a sensitivity of 63.2% and 80% specificity at 11.59 ng/ml and a sensitivity of 68.4% and 90% specificity at 10.35 ng/ml. At MS, responded NB patients were slightly increased up to 70%. This evaluation was confirmed by further decrease in cfDNA and NSE levels during intermediate chemotherapy in comparison with early stage. CONCLUSION: The dynamic change of cfDNA was considered as a surrogate biomarker to evaluate tumor burden and MRD of NB during early and intermediate therapy periods.

The analysis of cell-free DNA concentrations and integrity in serum of initial and treated of lymphoma patients.

OBJECTIVE: To evaluate cell-free DNA (cfDNA) in plasma as a promising biomarker for lymphoma, altered levels of cfDNA and its association with clinical parameters are investigated in patients suffered from lymphomas. METHODS: Peripheral blood specimens were collected from 60 patients with lymphoma during initial diagnosis and those of another 107 patients with lymphoma during treated stage were also collected, 93 healthy volunteers were selected as control group. Quantitative PCR was used to detect cfDNA level in each group, cfDNA level in different groups was analyzed to understand its relationship with lymphoma patients' clinical features. After correlation analysis between cfDNA and clinical characteristics, Receiver operator characteristic curve was performed to analyze sensitivity and specificity of cfDNA and LDH. RESULTS: cfDNA concentration and integrity in initial stage of lymphoma patients were significantly higher than those in treated stage, and cfDNA concentration in treated phase was significantly higher than cfDNA concentration in control group. There was no significant difference in cfDNA integrity at treated stage compared with control group. There was no significant correlation between patient's age, gender, extranodal invasion and lymphoma pathological type and cfDNA concentration and integrity; In contrast, there was a significant correlation between ECOG score, LDH content, Ann Arbor stage, IPI, B-symptoms, Ki-67 expression and radiotherapy and cfDNA concentration and integrity, both at the time of initial diagnosis and treated stage. cfDNA concentration detection is an optimal diagnostic indicator, followed by cfDNA integrity detection, the sensitivity and specificity of both are superior to the traditional LDH detection. CONCLUSION: cfDNA level is significantly increased in lymphomas patient plasma and may help lymphoma screening. cfDNA level may serve as a potential indicator of lymphomas treatment efficacy.

Gene expression profiles analysis identifies a novel two-gene signature to predict overall survival in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy, however, specific tumor-associated genes and signaling pathways are yet to be deciphered. Differentially expressed genes (DEGs) were computed based on gene expression profiles from GSE32018, GSE56315, and The Cancer Genome Atlas (TCGA) DLBC. Overlapping DEGs were then evaluated for gene ontology (GO), pathways enrichment, DNA methylation, protein-protein interaction (PPI) network analysis as well as survival analysis. Seventy-four up-regulated and 79 down-regulated DEGs were identified. From PPI network analysis, majority of the DEGs were involved in cell cycle, oocyte meiosis, and epithelial-to-mesenchymal transition (EMT) pathways. Six hub genes including CDC20, MELK, PBK, prostaglandin D2 synthase (PTGDS), PCNA, and CDK1 were selected using the Molecular Complex Detection (MCODE). CDC20 and PTGDS were able to predict overall survival (OS) in TCGA DLBC and in an additional independent cohort GSE31312. Furthermore, CDC20 DNA methylation negatively regulated CDC20 expression and was able to predict OS in DLBCL. A two-gene panel consisting of CDC20 and PTGDS had a better prognostic value compared with CDC20 or PTGDS alone in the TCGA cohort (P=0.026 and 0.039). Overall, the present study identified a set of novel genes and pathways that may play a significant role in the initiation and progression of DLBCL. In addition, CDC20 and PTGDS will provide useful guidance for therapeutic applications.

Plasma cell-free DNA quantification is highly correlated to tumor burden in children with neuroblastoma.

To evaluate plasma cell-free DNA (cfDNA) as a promising biomarker for neuroblastoma (NB) tumor burden. Seventy-nine eligible patients with newly diagnosed NB were recruited from Beijing Children's Hospital between April 2016 and April 2017. Additionally, from September 2011 to June 2017, 79 patients with stable NB were evaluated with a median follow-up time of 21 months. Approximately 2 mL of peripheral blood was drawn upon enrollment, and plasma cfDNA levels were measured via quantitative polymerase chain reaction (qPCR). Total cfDNA analysis was performed using the long interspersed nuclear element 1 (LINE-1) 79 bp fragment, and DNA integrity was calculated by the ratio of the LINE-1 300 bp fragment to the LINE-1 79 bp fragment. A total of 79 NB patients with a median age of 36 months comprised the group of newly diagnosed NB patients. The main primary tumor site was the retroperitoneal and adrenal region (81%). Three or more metastatic sites were found in 17.7% of patients. Stable NB patients older than 18 months comprised 98.7% of the stable NB patients. Neuron-specific enolase (NSE), lactate dehydrogenase (LDH), and cfDNA levels were dramatically increased in the newly diagnosed NB patients and significantly different from those in the stable NB patients. Moreover, the concentration of cfDNA was much higher in patients with larger tumors. By analyzing the area under the receiver operator characteristic (ROC) curve (AUC), the areas of total cfDNA, NSE, and LDH levels were 0.953, 0.929, and 0.906, respectively. The sensitivity and specificity data clarified that the level of circulating cfDNA in plasma can be considered as a reliable biomarker for describing tumor load in NB. The plasma cfDNA concentration was as good as the levels of LDH and NSE to discriminate the tumor burden in children with NB.

Soil heavy metal pollution and risk assessment associated with the Zn-Pb mining region in Yunnan, Southwest China.

The environmental assessment and identification of sources of heavy metals in Zn-Pb ore deposits are important steps for the effective prevention of subsequent contamination and for the development of corrective measures. The concentrations of eight heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in soils from 40 sampling points around the Jinding Zn-Pb mine in Yunnan, China, were analyzed. An environmental quality assessment of the obtained data was performed using five different contamination and pollution indexes. Statistical analyses were performed to identify the relations among the heavy metals and the pH in soils and possible sources of pollution. The concentrations of As, Cd, Pb, and Zn were extremely high, and 23, 95, 25, and 35% of the samples, respectively, exceeded the heavy metal limits set in the Chinese Environmental Quality Standard for Soils (GB15618-1995, grade III). According to the contamination and pollution indexes, environmental risks in the area are high or extremely high. The highest risk is represented by Cd contamination, the median concentration of which exceeds the GB15618-1995 limit. Based on the combination of statistical analyses and geostatistical mapping, we identified three groups of heavy metals that originate from different sources. The main sources of As, Cd, Pb, Zn, and Cu are mining activities, airborne particulates from smelters, and the weathering of tailings. The main sources of Hg are dust fallout and gaseous emissions from smelters and tailing dams. Cr and Ni originate from lithogenic sources.