Para-aortic lymph node metastasis from colorectal cancer is relatively rare. Recent studies have shown that curative para-aortic lymph node dissection can lead to similar prognoses as stage III colorectal cancer for selected patients. However, there are still many unresolved debates regarding the appropriate surgical indications, extent of lymph node dissection, and treatment principles for colorectal cancer patients with para-aortic lymph node metastasis. With the continuous improvement of laparoscopic colorectal surgery techniques, the previously complex and high-risk procedure of para-aortic lymph node dissection has now become a safe and feasible approach. However, there are still several challenges that need to be addressed in this field. It is imperative to conduct multicenter clinical studies to demonstrate the survival benefits of this surgical procedure into greater survival benefits. This will help generate more robust evidence in the field of evidence-based medicine.

Para-aortic lymph node metastasis from colorectal cancer is relatively rare. Recent studies have shown that curative para-aortic lymph node dissection can lead to similar prognoses as stage III colorectal cancer for selected patients. However, there are still many unresolved debates regarding the appropriate surgical indications, extent of lymph node dissection, and treatment principles for colorectal cancer patients with para-aortic lymph node metastasis. With the continuous improvement of laparoscopic colorectal surgery techniques, the previously complex and high-risk procedure of para-aortic lymph node dissection has now become a safe and feasible approach. However, there are still several challenges that need to be addressed in this field. It is imperative to conduct multicenter clinical studies to demonstrate the survival benefits of this surgical procedure into greater survival benefits. This will help generate more robust evidence in the field of evidence-based medicine.

Objective:To analyze the clinical characteristics of patients with acute glyphosate herbicide poisoning and the differences in the severity of poisoning.Methods:A retrospective analysis was performed on patients with acute glyphosate herbicide poisoning admitted to the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2020. The general information, exposure time, poisoning dose, poisoning cause, poisoning route, clinical manifestations, laboratory examination results during hospitalization, treatment measures, hospital stays and prognosis of the patients were collected. The patients were graded according to the poisoning severity scoring standard of Chinese Expert Consensus on Diagnosis and Treatment of Acute Poisoning in 2016. The highest severity score during hospitalization was used as the final grade. According to the final grade, asymptomatic and mild patients were included in the mild group, and moderate, severe and death patients were included in the severe group. The independent sample T test or Mann-Whitney U test was used for measurement data, and χ2 test or Fisher's exact test was used for counting data. The differences of general data and clinical data between the two groups were compared. Results:According to the inclusion and exclusion criteria, 83 patients with acute glyphosate herbicide poisoning were selected as the study subjects. All patients survived, mainly mild poisoning (56.6%), with a male to female ratio of 33∶50, and an average age of 39 years. The number of poisoning cases increased yearly (the highest in 2019), and most cases occurred in spring and summer. The main cause of poisoning was suicide (71.1%), direct oral administration (83.1%) was the primary route of poisoning, and the dominating clinical manifestations were digestive symptoms (71.1%). Laboratory tests showed increased white blood cell count (WBC), neutrophil percentage (NEUT %) and D-dimer, and decreased hemoglobin and potassium. Compared with the mild group, patients in the severe group were older [(51±17) years vs. (35±19) years], had a higher proportion of suicide and direct oral administration, a longer hospital stay [8.0 (4.8, 12.0) d vs. 3.0 (2.0, 5.5) d], a higher dose of poisoning [200.0 (50.0, 200.0) mL vs. 30.0 (11.3, 57.5) mL], and higher NEUT % within 24 h of admission [(83.4±10.4) vs. (73.2±12.8)]. The increase of WBC, NEUT %, aspartate aminotransferase, prothrombin time, D-dimer and the decrease of serum potassium were more common in the severe group than the mild group, with statistical significance (all P<0.05). Conclusions:The number of patients with acute glyphosate herbicide poisoning is increasing yearly. Generally, the condition is mild and the prognosis is satisfying. The severity is more serious in the middle-aged and elderly patients andthose with direct oral administration, high toxic dose, and high NEUT % within 24 h of admission. Severe poisoning is more likely to cause changes in laboratory indicators.

Objective To investigate the effect of tail vein transplantation of human amniotic mesenchymal stem cells (hAMSCs) with different transforming growth factor (TGF)-β expressions on recovery of sciatic nerve function in peripheral nerve xenotransplantation mice.Methods The hAMSCs were isolated from amnion membranes by healthy mother donors and identified by fluorescence activated cell sorter.The up-regulated and down-regulated TGF-β lentiviral plasmids were constructed and transfected into the purified hAMSCs;hAMSCs with stable up-regulated or down-regulated TGF-β expression were constructed.The sciatic nerves of C57BL/6 mice were isolated and cut out,and sciatic nerves of SD rats were isolated and transplanted into the sciatic nerve defected C57BL/6 mice to construct peripheral nerve xeno-transplanted mice models;these mice models were divided into 4 groups (n=10)according to random number table:control group,hAMSCs treatment group,high-expressed TGF-βhAMSCs treatment group,and low-expressed TGF-β hAMSCs treatment group;one d before modeling,phosphate buffer saline (PBS) or hAMSCs re-suspension were drawn with a syringe and slowly pushed into the tail veins of mice for transplantation treatment;14 d after treatment,DigGait analysis system was used to evaluate the recovery of sciatic nerve function in each group of mice.Result Fourteen d after treatment,the sciatic nerve function index (SFI) of the high-expressed TGF-β hAMSCs treatment group (-25.820±0.286) was significantly higher than that of the low-expressed TGF-β hAMSCs treatment group (-33.413±0.920) and hAMSCs treatment group (-30.755±0.421,P＜0.05).Conclusion The tail vein transplantation of hAMSCs with TGF-β high expression can effectively improve the sciatic nerve function in peripheral nerve xenotransplantation mice,which may be a new breakthrough in the treatment of peripheral nerve defects.

OBJECTIVE: To explore the efficacy of radiotherapy combined with surgery for locally advanced rectal mucinous adenocarcinoma. METHODS: Clinical data of patients with locally advanced rectal mucinous adenocarcinoma (T3-4 and/or N+) diagnosed by postoperative pathology from 1992 to 2013 were retrieved from the US Surveillance, Epidemiology, and End Results (SEER) database. Patients with local excision only, tumor biopsy or combined organ excision and incomplete follow-up information were excluded. All the enrolled patients were divided into three groups according to different treatments, including surgery alone (SA) group, preoperative radiotherapy combined with surgery (RT+S) group and surgery combined with postoperative radiotherapy (S+RT) group. The extracted data included basic data of patients and tumor, treatment status, and follow-up results. The χ² test was used to compare the count data. Kaplan-Meier method was used to draw the survival curve and calculate the survival rate. The survival was analyzed and compared by Log-rank test. The R language 2.8.1 was used to match the patients as 1:1 pairing through the propensity score matching (PSM). The matching variables included gender, age at diagnosis, year at diagnosis, ethnicity, degree of tissue differentiation, TNM stage, depth of invasion, making the baseline data of subgroups comparable. The Cox proportional hazard model was used for multivariate analysis of prognostic factors. RESULTS: A total of 2 149 patients with locally advanced rectal mucinous adenocarcinoma were enrolled in the study, including 1 255 males (58.4%) and 894 females (41.6%). There were 706 patients (32.9%) in the SA group, 772 patients (35.9%) in the RT+S group and 671 patients (31.2%) in the S+RT group. In SA, RT+S and S+RT groups, the median overall survival time was 39, 85, and 74 months respectively; the 5-year overall survival (OS) rate was 38.7%, 56.5%, and 55.2% respectively; the median cancer-specific survival (CSS) time was 86, 127, and 111 months respectively, and the 5-year CSS rate was 53.7%, 62.2% and 60.7% respectively. In comparison among the 3 groups, the 5-year OS rate and CSS rate in the SA group were significantly lower than those in the RT+S group and S+RT group (all P<0.001); the 5-year OS rate and CSS rate between RT+S group and S+RT group were not significantly different (P=0.166 and 0.392,respectively). After the baseline data of subgroups were corrected through PSM, the 5-year OS rate and CSS rate in the SA group (n=375) were significantly lower than those in the RT+S group (n=375)(OS:40.1% vs. 54.5%, P<0.001; CSS:54.3% vs. 63.3%, P=0.023). The 5-year OS rate and CSS rate in the SA group (n=403) were also lower than those in the S+RT group (n=403) (OS:37.4% vs. 54.7%,P<0.001;CSS:51.6% vs. 61.0%,P=0.031). The 5-year OS rate and CSS rate between RT+S group (n=363) and S+RT group (n=363) were not significantly different (OS:51.7% vs. 55.5%, P=0.789; CSS:57.7% vs. 60.5%, P=0.484). Cox multivariate analysis showed that radiotherapy (HR=0.845, 95%CI: 0.790 to 0.903, P=0.001) was an independent prognostic factor for OS of locally advanced rectal mucinous adenocarcinoma; radiotherapy (HR=0.907, 95% CI: 0.835 to 0.985, P=0.021) was also an independent prognostic factor affecting CSS in patients with locally advanced rectal mucinous adenocarcinoma. CONCLUSION As compared with surgery alone, surgery combined with preoperative or postoperative radiotherapy is beneficial to the long-term survival of patients with locally advanced rectal mucinous adenocarcinoma.
Adenocarcinoma, Mucinous ; pathology ; radiotherapy ; surgery ; therapy ; Female ; Humans ; Male ; Neoplasm Staging ; Proctectomy ; Prognosis ; Radiotherapy, Adjuvant ; Rectal Neoplasms ; pathology ; radiotherapy ; surgery ; therapy ; Retrospective Studies ; SEER Program ; Survival Analysis ; Treatment Outcome

Objective To investigate the effects of the number of harvested lymph nodes in neoadjuvant chemoradiotherapy (nCRT) combined with surgery on prognosis of middle-low rectal cancer.Methods The retrospective case-control study was conducted.The clinicopathological data of 373 patients with middle-low rectal cancer who underwent nCRT combined with surgery in the Fujian Medical University Union Hospital from January 2009 to December 2013 were collected.There were 241 males and 132 females,aged from 26 to 81 years,with the age of (55 ± 11) years.Observation indicators:(1) treatment situations;(2) follow-up and survival;(3)influencing factors for the number of harvested lymph nodes;(4) prognostic analysis of the different number of harvested lymph nodes as cut-off for grouping;(5) stratified analysis.Follow-up using telephone interview and outpatient examination was performed to detect postoperative survival of patients once every three months within postoperative 2 years and once every 6 months during the postoperative third year up to March 2016.The endpoint of follow-up was tumor recurrence,retastasis or death.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was done using the independent sample t test.Measurement data with skewed distribution were represented as M (range),and comparison between groups was done using the Kruska1-Wallis H test.Count data was described as absolute numbers.Univariate and multivariate analyses were done by the multiple linear regression model.Survival rate was calculated by the Kaplan-Meier method,and Logrank test was used for survival analysis.Results (l) Treatment situations:373 patients underwent nCRT combined with surgery,including 329 combined with sphincter-sparing rectal resection and 44 combined with abdominoperineal rectal resection.The number of harvested lymph nodes was 12 ± 6 in 373 patients.There were 185 patients with the number of harvested lymph nodes ＜ 12 and 188 with the number of harvested lymph nodes ≥ 12.(2) Follow-up and survival:373 patients were followed up for 5-77 months,with a median follow-up time of 43 months.During the follow-up,the 1-,3-,5-year disease-free survival rates were respectively 90.4％,76.3％,and 67.5％ in the 373 patients.(3) Influencing factors for the number of harvested lymph nodes:univariate analysis showed that distance between the tumor and anal verge,tumor diameter,tumor pathological N staging,and regression grade of rectal cancer were associated factors for the number of harvested lymph nodes (t =3.156,2.992,x2=8.183,10.839,P＜0.05).Multivariate analysis showed that distance between the tumor and anal verge,regression grade of rectal cancer,and tumor pathological N staging were independent factors for the number of harvested lymph nodes (t=3.308,2.690,2.584,95％ confidence interval:0.808-3.180,0.446-2.873,0.332-2.448,P＜0.05).(4) Prognostic analysis of the different number of harvested lymph nodes as cut-off for grouping:with the number of harvested lymph nodes of 6,7,8,9,10,11,12,13,14,15,and 16 as cut-off for grouping,there was no significant difference in the 3-year disease-free survival rate,cumulative local recurrence rate,and cumulative distant metastasis rate between ＜6 group and ≥6 group,between ＜7 group and ≥7 group,between＜8 group and ≥8 group,between ＜9 group and ≥9 group,between ＜10 group and ≥ 10 group,between ＜11 group and ≥ll group,between ＜12 group and ≥12 group,between ＜13 group and ≥13 group,between ＜ 14 group and ≥ 14 group,between ＜ 15 group and ≥ 15 group,between ＜ 16 group and ≥ 16 group,respectively (P＞0.05).(5) Stratified analysis:with the number of harvested lymph nodes of 7,8,9,and 10 as cut-off for grouping in 45 of 373 patients with Ⅱ-Ⅲ regression grade of rectal cancer and negative lymph nodes (NO staging),there was no significant difference in the 3-year disease-free survival rate between ＜7 group and ≥ 7group,between ＜8 group and ≥8 group,between ＜9 group and ≥9 group,between＜10 group and ≥ 10 group,respetively (x2 =3.946,5.346,6.375,4.297,P＜0.05).Conclusions The number of lymph nodes as 12 is not the independent factor for prognosis of patients with middle-low rectal cancer after nCRT combined with surgery.The number of harvested lymph nodes as 7 to 10 is the important factor for evaluating the prognosis of middle-low rectal cancer patients with Ⅱ-Ⅲ regression grade of rectal cancer and negative lymph nodes after nCRT combined with surgery.

Objective: To screen out the potential gene biomarkers to predict responses to neoadjuvant chemoradiotherapy (CRT) in patients with rectal cancer and to explore the main downstream pathways of resistance. Methods: The gene expression profiles (GSE35452) of locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy from 46 specimens (24 responders, TRG 0/1, and 22 non-responders, TRG 2/3) were downloaded from the GEO database. The differentially expressed genes were identified to screen out the potential biomarkers by use of the GCBI platform. GO and KEGG pathways enrichment analysis were performed to integrate enrichment results of differentially expressed genes. Signal-signal interaction network was constructed and analyzed to screen out potential main downstream pathways. Results: A total of 1079 differentially expressed genes were screened, including 657 up-regulated and 422 down-regulated ones. Among these genes, REG4 had the maximum fold change value of -6.029 491. In GO term, these differentially expressed genes were mainly enriched in molecule metabolic process, cell cycle, DNA-dependent transcription, signal transduction and apoptotic process. The KEGG pathways enrichment analysis showed that the differentially expressed genes were enriched in 65 KEGG pathways, including metabolic pathways, cell cycle and metabolism pathways. Signal-signal interaction network analysis showed that MAPK signaling pathway and cell cycle pathway might play a determinant role in the development of neoadjuvant chemoradiotherapy resistance. Further analysis showed that CDKN1B, CDKN2A, RBL1, TFDP1, CCND2, CCNE2, CDC6 and CDK6 in cell cycle might induce chemoradiotherapy resistance by blocking G1/S phase cell cycle arrest, decreasing the apoptosis of tumor cells and increasing S phase ratio of chemoradiotherapy resistance. Conclusion G1/S phase cell cycle arrest blocking plays an important role in the development of chemoradiotherapy resistance in patients with rectal cancer. Moreover, the key genes, such as REG4, may be useful in predicting responses to neoadjuvant chemoradiotherapy.

Objective To screen out the potential gene biomarkers to predict responses to neoadjuvant chemoradiotherapy (CRT) in patients with rectal cancer and to explore the main downstream pathways of resistance. Methods The gene expression profiles (GSE35452) of locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy from 46 specimens (24 responders, TRG 0/1, and 22 non?responders, TRG 2/3) were downloaded from the GEO database. The differentially expressed genes were identified to screen out the potential biomarkers by use of the GCBI platform. GO and KEGG pathways enrichment analysis were performed to integrate enrichment results of differentially expressed genes. Signal?signal interaction network was constructed and analyzed to screen out potential main downstream pathways. Results A total of 1079 differentially expressed genes were screened, including 657 up?regulated and 422 down?regulated ones. Among these genes, REG4 had the maximum fold change value of –6.029 491. In GO term, these differentially expressed genes were mainly enriched in molecule metabolic process, cell cycle, DNA?dependent transcription, signal transduction and apoptotic process. The KEGG pathways enrichment analysis showed that the differentially expressed genes were enriched in 65 KEGG pathways, including metabolic pathways, cell cycle and metabolism pathways. Signal?signal interaction network analysis showed that MAPK signaling pathway and cell cycle pathway might play a determinant role in the development of neoadjuvant chemoradiotherapy resistance. Further analysis showed that CDKN1B, CDKN2A, RBL1, TFDP1, CCND2, CCNE2, CDC6 and CDK6 in cell cycle might induce chemoradiotherapy resistance by blocking G1/S phase cell cycle arrest, decreasing the apoptosis of tumor cells and increasing S phase ratio of chemoradiotherapy resistance. Conclusion G1/S phase cell cycle arrest blocking plays an important role in the development of chemoradiotherapy resistance in patients with rectal cancer. Moreover, the key genes, such as REG4, may be useful in predicting responses to neoadjuvant chemoradiotherapy.

Objective To screen out the potential gene biomarkers to predict responses to neoadjuvant chemoradiotherapy (CRT) in patients with rectal cancer and to explore the main downstream pathways of resistance. Methods The gene expression profiles (GSE35452) of locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy from 46 specimens (24 responders, TRG 0/1, and 22 non?responders, TRG 2/3) were downloaded from the GEO database. The differentially expressed genes were identified to screen out the potential biomarkers by use of the GCBI platform. GO and KEGG pathways enrichment analysis were performed to integrate enrichment results of differentially expressed genes. Signal?signal interaction network was constructed and analyzed to screen out potential main downstream pathways. Results A total of 1079 differentially expressed genes were screened, including 657 up?regulated and 422 down?regulated ones. Among these genes, REG4 had the maximum fold change value of –6.029 491. In GO term, these differentially expressed genes were mainly enriched in molecule metabolic process, cell cycle, DNA?dependent transcription, signal transduction and apoptotic process. The KEGG pathways enrichment analysis showed that the differentially expressed genes were enriched in 65 KEGG pathways, including metabolic pathways, cell cycle and metabolism pathways. Signal?signal interaction network analysis showed that MAPK signaling pathway and cell cycle pathway might play a determinant role in the development of neoadjuvant chemoradiotherapy resistance. Further analysis showed that CDKN1B, CDKN2A, RBL1, TFDP1, CCND2, CCNE2, CDC6 and CDK6 in cell cycle might induce chemoradiotherapy resistance by blocking G1/S phase cell cycle arrest, decreasing the apoptosis of tumor cells and increasing S phase ratio of chemoradiotherapy resistance. Conclusion G1/S phase cell cycle arrest blocking plays an important role in the development of chemoradiotherapy resistance in patients with rectal cancer. Moreover, the key genes, such as REG4, may be useful in predicting responses to neoadjuvant chemoradiotherapy.

Objective To screen out the potential gene to predict regional lymph node metastasis after neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC) and develop a 6-gene model using an artificial neural network (ANN).Methods The gene expression profiles (GSE46862) of locally advanced rectal cancer undergoing preoperative chemoradiotherapy from 64 specimens (21 with ypN-and 43 with ypN+) were downloaded from the gene expression omnibus (GEO) database.The differentially expressed genes were identified to screen out the potential biomarkers through the Gene-Cloud of Biotechnology Information (GCBI) platform.The top 6 genes were screened out for building model.An ANN model was trained and validated using the SPSS Modeler software.The study samples were allocated randomly into the training sample group and testing sample group with a 7∶3 ratio.The training samples and testing samples were respectively used for building an ANN model and independent back-substitution test.Observation indicators:(1) screening results of differentially expressed genes;(2) analysis results of ANN model.The receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to evaluate the predictive abilities of ANN and each biomarker.Results (1) Screening results of differentially expressed genes:A total of 50 genes were screened.Six top genes included IL6,AKR1B1,AREG,SELE,ROBO1 and CD274.(2) Analysis results of ANN model:Six top genes were selected to construct a three-layer ANN model with a 7-5-2 structure.The IL6 made the greatest effect on the ANN model,followed by ROBO1,AKR1B1,AREG,CD274 and SELE.The AUC was 0.929.The sensitivity and specificity of ANN model were 96.7％ and 85.7％,and accuracy of training samples was 93.2％.In the independent back-substitution test,sensitivity and specificity were 92.3％ and 85.7％,and accuracy of testing samples was 90.0％.Conclusion The prediction ANN model based on multiple molecular markers (IL6,ROBO1,AKR1B1,AREG,CD274 and SELE) for regional lymph node metastases in LARC patients after CRT would be beneficial in selecting potential candidates for rectum-preserving surgery following CRT for LARC.