Diagnosis of colorectal cancer based on folate receptor-positive circulating tumor cell analysis: a retrospective cohort study.

BACKGROUND: Early diagnosis and treatment are crucial to improve the prognosis of colorectal cancer (CRC). At present, there is a lack of an accurate CRC screening factor. We conducted folate receptor-positive circulating tumor cell analysis (FR + CTC analysis) in distinguishing CRC from benign colorectal diseases to evaluate the diagnostic efficiency. METHODS: Clinical data of patients admitted to The First Affiliated Hospital of Anhui Medical University from January 2021 to July 2022 were retrospectively collected. Levels of FR + CTC and other indicators were analyzed. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of these molecular biomarkers. RESULTS: Data of 103 patients with CRC and 54 patients with benign colorectal diseases were collected. FR + CTC levels were observed significantly higher in CRC patients than in patients with benign colorectal diseases (P < 0.001). FR + CTC level was correlated with tumor diameter, differentiation, T-stage, pathological stage, clinical stage, and intravascular tumor thrombus in patients with CRC (P < 0.05). The optimal cutoff value of FR + CTC level for diagnosing CRC patients was 7.66 FU/3 ml, with a sensitivity of 85.4%, a specificity of 74.1%, and an Area Under Curve (AUC) of 0.855 (95% CI 0.77-0.923). In < 50-years old patients with CRC, the diagnostic efficiency of FR + CTC was excellent, with an AUC of 0.936 (95% CI 0.877-0.995). CONCLUSION: FR + CTC counting has excellent diagnostic efficiency in screening of CRC. FR + CTC count can also predict the tumor stage of CRC patients before surgery, and guide the choice of treatment.

Prognostic significance of post-preoperative tumor markers increments in patients with non-metastatic gastric cancer.

PURPOSE: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the most common tumor markers detected before and after gastric cancer (GC) surgery. However, the impact of post-preoperative CEA/CA19-9 increments on prognosis of GC remains unclear. In addition, there is no research incorporating post-preoperative CEA/CA19-9 increments into the prognostic model. METHODS: Patients who underwent radical gastrectomy for GC at the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital from January 2013 to December 2017 were enrolled and divided into the discovery and validation cohort. Prognostic value of post-preoperative CEA/CA19-9 increments and preoperative CEA/CA199 levels were assessed by Kaplan-Meier log-rank analysis and compared by time-dependent receiver operating characteristic (t-ROC) curves. Multivariate Cox regression analysis was applied to establish the nomogram. The performance of the prognostic model was validated by the concordance index (C-index), calibration curve, and ROC curve analysis. RESULTS: A total of 562 GC patients were included in this study. Overall survival (OS) rates decreased with an increasing number of incremental tumor markers after surgery. The t-ROC curves implied that the prognostic ability of the number of incremental post-preoperative tumor markers was superior to that of the number of positive preoperative tumor markers. Cox regression analysis suggested that the number of incremental post-preoperative tumor markers was an independent prognostic factor. The nomogram incorporated with the post-preoperative CEA/CA19-9 increments showed reliable accuracy. CONCLUSIONS: Incremental post-preoperative CEA/CA19-9 were indicator of poor prognosis of GC. The prognostic value of post-preoperative CEA/CA19-9 increments exceed that of preoperative CEA/CA19-9 levels.

Prediction of overall survival after radical gastrectomy using nomograms created by tumor markers.

Prediction of prognosis after radical resection of gastric cancer has not been well established. Therefore, we aimed to establish a prognostic model based on a new score system of patients with gastric cancer. A total of 1235 patients who underwent curative gastrectomy at our hospital from October 2015 to April 2017 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. Construction of the nomogram was based on Cox proportional hazard regression models. The construction of the new score models was analyzed by the receiver operating characteristic curve (ROC curve), calibration curve, and decision curve. Multivariate analysis showed that tumor size, T, N, carcinoembryonic antigen, CA125, and CA19-9 were independent prognostic factors. The new score model had a greater AUC (The area under the ROC curve) than other systems, and the C-index of the nomogram was highly reliable for evaluating the survival of patients with gastric cancer. Based on the tumor markers and other clinical indicators, we developed a precise model to predict the prognosis of patients with gastric cancer after radical surgery. This score system can be helpful to both surgeons and patients.

Effects and mechanisms of trifluridine alone or in combination with cryptotanshinone in inhibiting malignant biological behavior of gastric cancer.

BACKGROUND: The incidence of gastric cancer (GC) ranks fourth among all malignant tumors worldwide, and the fatality rate ranks second among all malignant tumors. Several Chinese traditional medicines have been used in the treatment of advanced gastric cancer. This study aims to investigate the effect of combinational use of natural product cryptotanshinone (CTS) with anti-cancer drug trifluorothymidine (FTD) in GC. METHODS: Cell Counting Kit-8 assay was used to detect the inhibitory effect of the combinational or separate use of FTD and CTS on the growth of HGC-27 and AGS GC cells. The combined index of FTD and CTS was calculated using CompuSyn software. To understand the mechanism, we applied flow cytometry to study the cell cycle and cell apoptosis after treatment. We also investigated the amount of FTD incorporated into the DNA by immunofluorescence assay. The expression of relevant proteins was monitored using western blot. Furthermore, the effect of using TAS-102 in combination with CTS was studied in xenograft tumor nude mice model. RESULTS: FTD and CTS inhibited the growth of GC cells in a dose-dependent manner, respectively. They both exhibited low to sub-micromolar potency in HGC-27 and AGS cells. The combination of FTD and CTS showed synergistic anticancer effect in HGC-27 cells and AGS cells. Our mechanism studies indicate that FTD could block HGC-27 cells at G2/M phase, while CTS could block HGC-27 cells at G1/G0 phase, while FTD combined with CTS could mainly block HGC-27 cells at G2 phase. FTD in combination with CTS significantly increased the apoptosis of HGC-27 cells. We observed that CTS treatment increased the incorporation of FTD into the DNA HGC-27 cell. FTD treatment activated STAT3 phosphorylation in HGC-27 cells, while CTS treatment down-regulated the concentration of p-STAT3. Interestingly, the combination of CTS and FTD reduced STAT3 phosphorylation induced by FTD. In the in vivo experiments, we observed that the combination of TAS-102 with CTS was significantly more potent than TAS-102 on tumor growth inhibition. CONCLUSIONS: FTD combined with CTS has a synergistic anti-gastric cancer effect as shown by in vitro and in vivo experiments, and the combined treatment of FTD and CTS will be a promising treatment option for advanced gastric cancer.

Nomogram established using risk factors of early gastric cancer for predicting the lymph node metastasis.

BACKGROUND: For the prognosis of patients with early gastric cancer (EGC), lymph node metastasis (LNM) plays a crucial role. A thorough and precise evaluation of the patient for LNM is now required. AIM: To determine the factors influencing LNM and to construct a prediction model of LNM for EGC patients. METHODS: Clinical information and pathology data of 2217 EGC patients downloaded from the Surveillance, Epidemiology, and End Results database were collected and analyzed. Based on a 7:3 ratio, 1550 people were categorized into training sets and 667 people were assigned to testing sets, randomly. Based on the factors influencing LNM determined by the training sets, the nomogram was drawn and verified. RESULTS: Based on multivariate analysis, age at diagnosis, histology type, grade, T-stage, and size were risk factors of LNM for EGC. Besides, nomogram was drawn to predict the risk of LNM for EGC patients. Among the categorical variables, the effect of grade (well, moderate, and poor) was the most significant prognosis factor. For training sets and testing sets, respectively, area under the receiver-operating characteristic curve of nomograms were 0.751 [95% confidence interval (CI): 0.721-0.782] and 0.786 (95%CI: 0.742-0.830). In addition, the calibration curves showed that the prediction model of LNM had good consistency. CONCLUSION: Age at diagnosis, histology type, grade, T-stage, and tumor size were independent variables for LNM in EGC. Based on the above risk factors, prediction model may offer some guiding implications for the choice of subsequent therapeutic approaches for EGC.

Efficacy and outcome of extensive intraoperative peritoneal lavage plus surgery vs surgery alone with advanced gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors. After resection, one of the major problems is its peritoneal dissemination and recurrence. Some free cancer cells may still exist after resection. In addition, the surgery itself may lead to the dissemination of tumor cells. Therefore, it is necessary to remove residual tumor cells. Recently, some researchers found that extensive intraoperative peritoneal lavage (EIPL) plus intraperitoneal chemotherapy can improve the prognosis of patients and eradicate peritoneal free cancer for GC patients. However, few studies explored the safety and long-term outcome of EIPL after curative gastrectomy. AIM: To evaluate the efficacy and long-term outcome of advanced GC patients treated with EIPL. METHODS: According to the inclusion and exclusion criteria, a total of 150 patients with advanced GC were enrolled in this study. The patients were randomly allocated to two groups. All patients received laparotomy. For the non-EIPL group, peritoneal lavage was washed using no more than 3 L of warm saline. In the EIPL group, patients received 10 L or more of saline (1 L at a time) before the closure of the abdomen. The surviving rate analysis was compared by the Kaplan-Meier method. The prognostic factors were carried out using the Cox appropriate hazard pattern. RESULTS: The basic information in the EIPL group and the non-EIPL group had no significant difference. The median follow-up time was 30 mo (range: 0-45 mo). The 1- and 3-year overall survival (OS) rates were 71.0% and 26.5%, respectively. The symptoms of ileus and abdominal abscess appeared more frequently in the non-EIPL group (P < 0.05). For the OS of patients, the EIPL, Borrmann classification, tumor size, N stage, T stage and vascular invasion were significant indicators. Then multivariate analysis revealed that EIPL, tumor size, vascular invasion, N stage and T stage were independent prognostic factors. The prognosis of the EIPL group was better than the non-EIPL group (P < 0.001). The 3-year survival rate of the EIPL group (38.4%) was higher than the non-EIPL group (21.7%). For the recurrence-free survival (RFS) of patients, the risk factor of RFS included EIPL, N stage, vascular invasion, type of surgery, tumor location, Borrmann classification, and tumor size. EIPL and tumor size were independent risk factors. The RFS curve of the EIPL group was better than the non-EIPL group (P = 0.004), and the recurrence rate of the EIPL group (24.7%) was lower than the non-EIPL group (46.4%). The overall recurrence rate and peritoneum recurrence rate in the EIPL group was lower than the non-EIPL group (P < 0.05). CONCLUSION: EIPL can reduce the possibility of perioperative complications including ileus and abdominal abscess. In addition, the overall survival curve and RFS curve were better in the EIPL group.

Development and validation of a novel nomogram for predicting overall survival in gastric cancer based on inflammatory markers.

BACKGROUND: Nearly 66% of occurrences of gastric cancer (GC), which has the second-highest death rate of all cancers, arise in developing countries. In several cancers, the predictive significance of inflammatory markers has been established. AIM: To identify clinical characteristics and develop a specific nomogram to determine overall survival for GC patients. METHODS: Nine hundred and four GC patients treated at the First Affiliated Hospital of Anhui Medical University between January 2010 and January 2013 were recruited. Prognostic risk variables were screened for Cox analysis. The C index, receiver operator characteristic (ROC) curve, and decision curve analysis were used to evaluate the nomogram. RESULTS: Tumor node metastasis stage, carcinoembryonic antigen, systemic immune-inflammation index, and age were identified as independent predictive variables by multivariate analysis. Systemic immune-inflammation index value was superior to that of other inflammatory indicators. The ROC indicated the nomogram had a higher area under the curve than other factors, and its C-index for assessing the validation and training groups of GC patients was extremely reliable. CONCLUSION: We created a novel nomogram to forecast the prognosis of GC patients following curative gastrectomy based on blood markers and other characteristics. Both surgeons and patients can benefit significantly from this new scoring system.

Bioinformatics analysis of ferroptosis in spinal cord injury.

Ferroptosis plays a key role in aggravating the progression of spinal cord injury (SCI), but the specific mechanism remains unknown. In this study, we constructed a rat model of T10 SCI using a modified Allen method. We identified 48, 44, and 27 ferroptosis genes that were differentially expressed at 1, 3, and 7 days after SCI induction. Compared with the sham group and other SCI subgroups, the subgroup at 1 day after SCI showed increased expression of the ferroptosis marker acyl-CoA synthetase long-chain family member 4 and the oxidative stress marker malondialdehyde in the injured spinal cord while glutathione in the injured spinal cord was lower. These findings with our bioinformatics results suggested that 1 day after SCI was the important period of ferroptosis progression. Bioinformatics analysis identified the following top ten hub ferroptosis genes in the subgroup at 1 day after SCI: STAT3, JUN, TLR4, ATF3, HMOX1, MAPK1, MAPK9, PTGS2, VEGFA, and RELA. Real-time polymerase chain reaction on rat spinal cord tissue confirmed that STAT3, JUN, TLR4, ATF3, HMOX1, PTGS2, and RELA mRNA levels were up-regulated and VEGFA, MAPK1 and MAPK9 mRNA levels were down-regulated. Ten potential compounds were predicted using the DSigDB database as potential drugs or molecules targeting ferroptosis to repair SCI. We also constructed a ferroptosis-related mRNA-miRNA-lncRNA network in SCI that included 66 lncRNAs, 10 miRNAs, and 12 genes. Our results help further the understanding of the mechanism underlying ferroptosis in SCI.

Identification of necroptosis-related genes for predicting prognosis and exploring immune infiltration landscape in colon adenocarcinoma.

Background: Necroptosis is a recently discovered form of cell death that plays an important role in the occurrence and development of colon adenocarcinoma (COAD). Our study aimed to construct a risk score model to predict the prognosis of patients with COAD based on necroptosis-related genes. Methods: The gene expression data of COAD and normal colon samples were obtained from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to calculate the risk score based on prognostic necroptosis-related differentially expressed genes (DEGs). Based on the risk score, patients were classified into high- and low-risk groups. Then, nomogram models were built based on the risk score and clinicopathological features. Otherwise, the model was verified in the Gene Expression Omnibus (GEO) database. Additionally, the tumor microenvironment (TME) and the level of immune infiltration were evaluated by "ESTIMATE" and single-sample gene set enrichment analysis (ssGSEA). Functional enrichment analysis was carried out to explore the potential mechanism of necroptosis in COAD. Finally, the effect of necroptosis on colon cancer cells was explored through CCK8 and transwell assays. The expression of necroptosis-related genes in colon tissues and cells treated with necroptotic inducers (TNFα) and inhibitors (NEC-1) was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The risk score was an independent prognostic risk factor in COAD. The predictive value of the nomogram based on the risk score and clinicopathological features was superior to TNM staging. The effectiveness of the model was well validated in GSE152430. Immune and stromal scores were significantly elevated in the high-risk group. Moreover, necroptosis may influence the prognosis of COAD via influencing the cancer immune response. In in-vitro experiments, the inhibition of necroptosis can promote proliferation and invasion ability. Finally, the differential expression of necroptosis-related genes in 16 paired colon tissues and colon cancer cells was found. Conclusion: A novel necroptosis-related gene signature for forecasting the prognosis of COAD has been constructed, which possesses favorable predictive ability and offers ideas for the necroptosis-associated development of COAD.

Model established based on blood markers predicts overall survival in patients after radical resection of types II and III adenocarcinoma of the esophagogastric junction.

BACKGROUND: In recent years, the incidence of types II and III adenocarcinoma of the esophagogastric junction (AEG) has shown an obvious upward trend worldwide. The prognostic prediction after radical resection of AEG has not been well established. AIM: To establish a prognostic model for AEG (types II and III) based on routine markers. METHODS: A total of 355 patients who underwent curative AEG at The First Affiliated Hospital of Anhui Medical University from January 2014 to June 2015 were retrospectively included in this study. Univariate and multivariate analyses were performed to identify the independent risk factors. A nomogram was constructed based on Cox proportional hazards models. The new score models was analyzed by C index and calibration curves. The receiver operating characteristic (ROC) curve was used to compare the predictive accuracy of the scoring system and tumor-node-metastasis (TNM) stage. Overall survival was calculated using the Kaplan-Meier curve amongst different risk AEG patients. RESULTS: Multivariate analysis showed that TNM stage (hazard ratio [HR] = 2.286, P = 0.008), neutrophil-to-lymphocyte ratio (HR = 2.979, P = 0.001), and body mass index (HR = 0.626, P = 0.026) were independent prognostic factors. The new scoring system had a higher concordance index (0.697), and the calibration curves of the nomogram were reliable. The area under the ROC curve of the new score model (3-year: 0.725, 95% confidence interval [CI]: 0.676-0.777; 5-year: 0.758, 95%CI: 0.708-0.807) was larger than that of TNM staging (3-year: 0.630, 95%CI: 0.585-0.684; 5-year: 0.665, 95%CI: 0.616-0.715). CONCLUSION: Based on the serum markers and other clinical indicators, we have developed a precise model to predict the prognosis of patients with AEG (types II and III). The new prognostic nomogram could effectively enhance the predictive value of the TNM staging system. This scoring system can be advantageous and helpful for surgeons and patients.

A new evaluation model of a water conveyance channel based on Bayesian theory by integrating monitoring and detection information.

Channels are commonly used in long-distance water transfer projects, where landslides, collapses, or erosion may occur in its course of operation; thus, safety evaluation is conducted through monitoring and detection in its key and potentially hazardous areas. However, monitoring and detection information cannot comprehensively reflect the prominent problems of the safety state of the channel in terms of time and space. Therefore, studying how to realize the integration of monitoring and detection information is an important task for the safety evaluations of channels. In this paper, a method of integrating monitoring and detection information based on Bayesian theory is presented. The research shows that the fusion method of gathering monitoring and detection information based on Bayesian theory successfully captures the safety state of high-filling channels, and it can quantify and reduce uncertainty compared with fuzzy theory and the GA-BP neural network. By studying the influence of monitoring information on the safety of the channel, it is found that the horizontal displacement has a greater impact on the safety of the channel than the vertical displacement. A comparison of the results of fusing seven different monitoring points shows that the comprehensive utilization of horizontal and vertical displacement can improve the accuracy of the evaluation results. Compared to the safety coefficient calculated by the actual exploration, the error rate of the GA-BP neural network is 42.7%, and the fusion method based on Bayesian theory is 2.9%. The proposed method based on Bayesian theory can better use the detection information to recognize and understand the rock and soil in advance; hence, the evaluation results are more reliable and consistent with the actual engineering state.

Application value of biofluid-based biomarkers for the diagnosis and treatment of spinal cord injury.

Recent studies in patients with spinal cord injuries (SCIs) have confirmed the diagnostic potential of biofluid-based biomarkers, as a topic of increasing interest in relation to SCI diagnosis and treatment. This paper reviews the research progress and application prospects of recently identified SCI-related biomarkers. Many structural proteins, such as glial fibrillary acidic protein, S100-ß, ubiquitin carboxy-terminal hydrolase-L1, neurofilament light, and tau protein were correlated with the diagnosis, American Spinal Injury Association Impairment Scale, and prognosis of SCI to different degrees. Inflammatory factors, including interleukin-6, interleukin-8, and tumor necrosis factor α, are also good biomarkers for the diagnosis of acute and chronic SCI, while non-coding RNAs (microRNAs and long non-coding RNAs) also show diagnostic potential for SCI. Trace elements (Mg, Se, Cu, Zn) have been shown to be related to motor recovery and can predict motor function after SCI, while humoral markers can reflect the pathophysiological changes after SCI. These factors have the advantages of low cost, convenient sampling, and ease of dynamic tracking, but are also associated with disadvantages, including diverse influencing factors and complex level changes. Although various proteins have been verified as potential biomarkers for SCI, more convincing evidence from large clinical and prospective studies is thus required to identify the most valuable diagnostic and prognostic biomarkers for SCI.

Prognostic factors for disease-free survival in postoperative patients with hepatocellular carcinoma and construction of a nomogram model.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and has a high risk of invasion and metastasis along with a poor prognosis. AIM: To investigate the independent predictive markers for disease-free survival (DFS) in patients with HCC and establish a trustworthy nomogram. METHODS: In this study, 445 patients who were hospitalized in The First Affiliated Hospital of Anhui Medical College between December 2009 and December 2014 were retrospectively examined. The survival curve was plotted using the Kaplan-Meier method and survival was determined using the log-rank test. To identify the prognostic variables, multivariate Cox regression analyses were carried out. To predict the DFS in patients with HCC, a nomogram was created. C-indices and receiver operator characteristic curves were used to evaluate the nomogram's performance. Decision curve analysis (DCA) was used to evaluate the clinical application value of the nomogram. RESULTS: Longer DFS was observed in patients with the following characteristics: elderly, I-II stage, and no history of hepatitis B. The calibration curve showed that this nomogram was reliable and had a higher area under the curve value than the tumor node metastasis (TNM) stage. Moreover, the DCA curve revealed that the nomogram had good clinical applicability in predicting 3- and 5-year DFS in HCC patients after surgery. CONCLUSION: Age, TNM stage, and history of hepatitis B infection were independent factors for DFS in HCC patients, and a novel nomogram for DFS of HCC patients was created and validated.

Preventable lifestyle and eating habits associated with gastric adenocarcinoma: A case-control study.

Background: Besides the well-established risk factors for gastric adenocarcinoma (GaC), many other etiological factors remain largely unexplored. This large comprehensive case-control study aimed to investigate the preventable lifestyle and eating habits associated with GaC. Methods: Consecutive patients with primary microscopically-confirmed GaC diagnosed in 2016-2018 were matched by sex, age, height, and socioeconomic status at a 1:1 ratio with healthy controls. Association of GaC versus control with investigated factors was assessed using the multivariable-adjusted conditional logistic regression for paired samples. Results: Together 302 GaC patients and 302 healthy controls were investigated. Participants receiving higher education and those eating majorly vegetables had less frequently GaC. The majorly frying cooking habit was associated with a higher incidence of GaC. People complaining about poor sleep quality had more often GaC. The more often one smoked, the more often he/she had GaC. A higher frequency for having pickled food was associated with more frequent GaC, while having more frequently vegetables/fruit, beans, or kelps was associated with less often GaC. A greater preference for sour or bitter taste was associated with less frequent GaC. The frequencies of thin liquid intake after meal, swallowing hot food without adequate cooling, doing other things while eating, eating overnight food, and eating midnight snack were all positively associated with GaC, while going to bed regularly was associated with less often GaC. Conclusions: Education level, sleep quality, smoking, the frequencies of use of several foods and seasonings, the preference for specific tastes, and various eating and living habits were associated with GaC. The findings offer important hints for further prospective investigations and for easy effective GaC-preventative strategy-making.

MicroRNA changes of bone marrow-derived mesenchymal stem cells differentiated into neuronal-like cells by Schwann cell-conditioned medium.

Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and identified differentially expressed microRNAs in bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium, and explored targets and related pathways involved in their differentiation into neuronal-like cells. Primary bone marrow-derived mesenchymal stem cells were isolated from femoral and tibial bones, while primary Schwann cells were isolated from bilateral saphenous nerves. Bone marrow-derived mesenchymal stem cells were cultured in unconditioned (control group) and Schwann cell-conditioned medium (bone marrow-derived mesenchymal stem cell + Schwann cell group). Neuronal differentiation of bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium was observed by time-lapse imaging. Upon induction, the morphology of bone marrow-derived mesenchymal stem cells changed into a neural shape with neurites. Results of quantitative reverse transcription-polymerase chain reaction revealed that nestin mRNA expression was upregulated from 1 to 3 days and downregulated from 3 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. Compared with the control group, microtubule-associated protein 2 mRNA expression gradually increased from 1 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. After 7 days of induction, microRNA analysis identified 83 significantly differentially expressed microRNAs between the two groups. Gene Ontology analysis indicated enrichment of microRNA target genes for neuronal projection development, regulation of axonogenesis, and positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that Hippo, Wnt, transforming growth factor-beta, and Hedgehog signaling pathways were potentially associated with neural differentiation of bone marrow-derived mesenchymal stem cells. This study, which carried out successful microRNA analysis of neuronal-like cells differentiated from bone marrow-derived mesenchymal stem cells by Schwann cell induction, revealed key microRNAs and pathways involved in neural differentiation of bone marrow-derived mesenchymal stem cells. All protocols were approved by the Animal Ethics Committee of Institute of Radiation Medicine, Chinese Academy of Medical Sciences on March 12, 2017 (approval number: DWLI-20170311).

Abnormal DNA Methylation in Thoracic Spinal Cord Tissue Following Transection Injury.

BACKGROUND Spinal cord injury (SCI) is a serious disease with high disability and mortality rates, with no effective therapeutic strategies available. In SCI, abnormal DNA methylation is considered to be associated with axonal regeneration and cell proliferation. However, the roles of key genes in potential molecular mechanisms of SCI are not clear. MATERIAL AND METHODS Subacute spinal cord injury models were established in Wistar rats. Histological observations and motor function assessments were performed separately. Whole-genome bisulfite sequencing (WGBS) was used to detect the methylation of genes. Gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the DAVID database. Protein-protein interaction (PPI) networks were analyzed by Cytoscape software. RESULTS After SCI, many cavities, areas of necrotic tissue, and many inflammatory cells were observed, and motor function scores were low. After the whole-genome bisulfite sequencing, approximately 96 DMGs were screened, of which 50 were hypermethylated genes and 46 were hypomethylated genes. KEGG pathway analysis highlighted the Axon Guidance pathway, Endocytosis pathway, T cell receptor signaling pathway, and Hippo signaling pathway. Expression patterns of hypermethylated genes and hypomethylated genes detected by qRT-PCR were the opposite of WGBS data, and the difference was significant. CONCLUSIONS Abnormal methylated genes and key signaling pathways involved in spinal cord injury were identified through histological observation, behavioral assessment, and bioinformatics analysis. This research can serve as a source of additional information to expand understanding of spinal cord-induced epigenetic changes.

iTRAQ-based proteomics profiling of Schwann cells before and after peripheral nerve injury.

OBJECTIVES: Schwann cells (SCs) have a wide range of applications as seed cells in the treatment of nerve injury during transplantation. However, there has been no report yet on kinds of proteomics changes that occur in Schwann cells before and after peripheral nerve injury. MATERIALS AND METHODS: Activated Schwann cells (ASCs) and normal Schwann cells (NSCs) were obtained from adult Wistar rat sciatic nerves. After immunofluorescence identification, we identified differentially expressed proteins in the ASCs and NSCs using isobaric tags for relative and absolute quantitation (iTRAQ) combined with high-resolution Orbitrap liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). In addition, all the differentially expressed proteins were analyzed by Gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. Finally, several differentially expressed proteins were selected for Western blot verification. RESULTS: A total of 122 differentially expressed proteins in ASCs and NSCs were screened. GO analysis suggested that these different proteins are likely to accumulate in the cytoplasm and are associated with single-multicellular organism processes. The KEGG pathway analysis suggested that proteins related to purine metabolism were significantly enriched. The expression of Transmembrane glycoprotein NMB (GPNMB), Ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3), and other proteins were consistent with the proteomics data obtained by Western blot analysis. CONCLUSION: GPNMB, ENPP3, GFPT2, and other proteins may play an important role in the repair of peripheral nerve injury. This study may provide new insights into changes in SCs after peripheral nerve injury.

Can the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio be beneficial in predicting lymph node metastasis and promising prognostic markers of gastric cancer patients? Tumor maker retrospective study.

BACKGROUD: Inflammation can promote tumor growth, invasion, angiogenesis and even metastasis. Inflammatory markers have prognostic value in some malignancies. The aim of the present study was to examine whether neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) served as sensitive serum markers for predicting lymph node metastasis and prognostic factors in gastric cancer (GC) patients. METHODS: 904 consecutive patients who underwent radical total or subtotal gastrectomy between 2010 and 2011, were included in this study. The clinical utility of the NLR and PLR was evaluated by receiver operating characteristic (ROC) curves,Kaplan-Meier curves and Cox regression analyses were used to calculate the overall survival (OS) characteristics. RESULTS: We determined the cutoff values of NLR and PLR was 2.0 and 160 respectively according to the ROC curve. Both the NLR and PLR were significantly associated with LN (lymph node) metastasis, and high NLR and PLR groups were significantly associated with poor overall survival. Additionally, NLR and TNM stage were independent prognostic factors for overall survival, however, PLR had limited value. CONCLUSIONS: NLR and PLR levels may be valuable indexes for lymph node metastasis. Although both the PLR and NLR may have prognostic value of gastric cancer patients, NLR is better to predict overall survival than PLR.

A prospective appraisal of preoperative body mass index in D2-resected patients with non-metastatic gastric carcinoma and Siewert type II/III adenocarcinoma of esophagogastric junction: results from a large-scale cohort.

OBJECTIVE: To prospectively investigate associations of presurgical body mass index (BMI) with clinicopathological factors and its prognostic significance in radically D2-resected patients with non-metastasized gastric cancer (GC) and Siewert type II/III adenocarcinoma of esophagogastric junction (AEG). METHODS: A large prospective cohort consisting of radically-resected GC and AEG patients was analyzed. Follow-up was successful in 671 out of 700 patients, who were categorized into underweight (BMI<18.5), normal-weight (BMI=18.5-22.9), overweight (BMI=23-24.9), and obese (BMI≥25) groups according to Asian standards. BMI-associated factors were explored using multivariable logistic regression with adjustment. Cancer-specific survival analyses were conducted applying both univariable and multivariable Cox regression methods. RESULTS: Pre-operation, higher hemoglobin levels and smaller anemia proportions were observed in larger BMI groups. Higher BMI tended to be associated with higher neutrophil-lymphocyte ratios (NLRs). Patients with higher BMI had smaller tumors and more often stage I tumors, but longer surgical time and postsurgical stay. In multivariable analyses, higher hemoglobin levels, upper tumor location, poorer differentiation, and higher NLR were significantly associated with higher BMI. Overall, survival analyses revealed no significant role of BMI. However, in further stratifications after adjustment, compared to patients with normal BMI, obese patients had better survival in women, but worse in those with AEG; underweight was associated with reduced mortality risk in tumors differentiated well to moderately; overweight patients had increased death hazard when having thrombocytopenia. CONCLUSION: Overall, preoperative BMI had limited prognostic significance in operated GC patients. However, under specific conditions (e.g., female, AEG, good differentiation, and thrombocytopenia), BMI might indicate postoperative survival.

Docetaxel versus docetaxel plus cisplatin for non-small-cell lung cancer: a meta-analysis of randomized clinical trials.

OBJECTIVE: To compare the activity, efficacy and toxicity of docetaxel versus docetaxel plus cisplatin in patients with non-small-cell lung cancer. METHODS: A literature search was performed in the EMBASE, Medline, Cochrane Library, Web of Science, China National Knowledge Internet, Wan-fang databases. The trials that were found were then evaluated for eligibility. The Cochrane Collaboration's Review Manager software was used to perform the meta-analyses. RESULTS: Nine clinical trials including 1257 patients were included. The docetaxel plus cisplatin regimens had higher overall response rates compared with the docetaxel regimen (RR = 0.70; 95% CI, 0.61 to 0.80; P < 0.00001). No statistically significant difference was observed between the two regimens with respect to the one-year survival rate (RR = 1.04; 95% CI, 0.90 to 1.19; P = 0.62). Patients treated with the DP regimen were more likely to experience anemia, thrombocytopenia, nausea/vomiting, nephrotoxicity, hyponatremia, mucositis and treatment-related deaths compared with patients treated with docetaxel alone. No significant difference was observed between the two regimens with respect to the occurrence of neurotoxicity, diarrhea, fatigue, pneumonitis, neutropenia and leucopenia. CONCLUSIONS: The docetaxel plus cisplatin combination regimen resulted in a high response rate and a high adverse effect rate compared with docetaxel monochemotherapy for non-small-cell lung cancer.