【Objective】 To construct a nomogram survival prediction model for patients with locally advanced renal cell carcinoma based on SEER database (n=7893), so as to provide reference for future prognosis study. 【Methods】 Case data were downloaded from the SEER database, and divided into the experimental group and validation group with a ratio of 7∶3 by simple randomization.The clinical information was analyzed, independent risk factors influencing prognosis were screened, and the overall survival (OS) and tumor-specific survival (CSS) were mapped.Model performance was evaluated using consistency index, area under the receiver operating characteristic curve (AUC), internal and external validation, and calibration curves. 【Results】 Patients’ age, tumor size, disease progression tpye, TNM stage, number of positive lymph nodes, marital status and pathological type were significantly correlated with OS and CSS (P<0.01).Based on the above predictors, the internal verification AUC of the 1-, 3- and 5- year OS nomogram model was 0.809, 0.721 and 0.715, respectively.The internal validation AUC of the nomogram model for 1-, 3- and 5- year CSS was 0.802, 0.745 and 0.735, respectively.The external validation AUC of the OS nomogram model was 0.792, 0.628 and 0.620 at 1, 3 and 5 years, respectively, and the external validation AUC of CSS was 0.943, 0.803 and 0.737 at 1.3 and 5 years, respectively, showing good model differentiation and accuracy. 【Conclusion】 The prediction performance of the nomogram model is good, and it can provide reference for individualized treatment.

Objective:To investigate the characteristics of the CD8+T cells infiltration from the 4 sub-types in medulloblastoma(MB),to analyze the relationship between CD8+T cells infiltration and prog-nosis,to study the function of C-X-C motif chemokine ligand 11(CXCL11)and its receptor in CD8+T cells infiltration into tumors and to explore the potential mechanism,and to provide the necessary clinico-pathological basis for exploring the immunotherapy of MB.Methods:In the study,48 clinical MB sam-ples(12 cases in each of 4 subtypes)were selected from the multiple medical center from 2012 to 2019.The transcriptomics analysis for the tumor of 48 clinical samples was conducted on the NanoString Pan-Cancer 10360?Panel(NanoString Technologies).Immunohistochemistry(IHC)staining of formalin-fixed,paraffin-embedded sections from MB was carried out using CD8 primary antibody to analyze diffe-rential quantities of CD8+T cells in the MB four subtypes.Through bioinformatics analysis,the relation-ship between CD8+T cells infiltration and prognosis of the patients and the expression differences of various chemokines in the different subtypes of MB were investigated.The expression of CXCR3 receptor on the surface of CD8+T cells in MB was verified by double immunofluorescence staining,and the under-lying molecular mechanism of CD8+T cells infiltration into the tumor was explored.Results:The charac-teristic index of CD8+T cells in the WNT subtype of MB was relatively high,suggesting that the number of CD8+T cells in the WNT subtype was significantly higher than that in the other three subtypes,which was confirmed by CD8 immunohistochemical staining and Gene Expression Omnibus(GEO)database analysis by using R2 online data analysis platform.And the increase of CD8+T cells infiltration was posi-tively correlated with the patient survival.The expression level of CXCL11 in the WNT subtype MB was significantly higher than that of the other three subtypes.Immunofluorescence staining showed the presence of CXCL11 receptor,CXCR3,on the surface of CD8+T cells,suggesting that the CD8+T cells might be attracted to the MB microenvironment by CXCL11 through CXCR3.Conclusion:The CD8+T cells infiltrate more in the WNT subtype MB than other subtypes.The mechanism may be related to the activation of CXCL11-CXCR3 chemokine system,and the patients with more infiltration of CD8+T cells in tumor have better prognosis.This finding may provide the necessary clinicopathological basis for the regulatory mechanism of CD8+T cells infiltration in MB,and give a new potential therapeutic target for the future immunotherapy of MB.

Based on the analysis of heart rate variability(HRV),a prediction method for paroxysmal atrial fibrillation(PAF)attacks is proposed.A new adaptive filtering technique is used for smoothing and coarse graining of HRV,followed by entropy-based quantification of HRV complexity at multiple adaptive scales.After the features are normalized by Min-Max,feature subsets are selected by sequential forward selection method,and then input to support vector machine to identify HRV types and predict PAF attacks.Through 5-fold cross-validation on a set of 50 HRV sequences each lasting 5 minutes,the optimal prediction results are obtained:98%accuracy,100%sensitivity,96%specificity,demonstrating excellent performance.In addition,the experiment shows significant changes(P<0.05)in the complexity eigenvalues of HRV far away from and close to PAF at different frequency bands,reflecting alterations in nervous system regulation of cardiac rhythm and a decline in the ability to adapt to external environmental changes such as stress regulation.

BACKGROUND: Cholecystectomy is a standard surgery for patients suffering from gallbladder diseases, while the causal effects of cholecystectomy on colorectal cancer (CRC) and other complications are still unknown. METHODS: We obtained genetic variants associated with cholecystectomy at a genome-wide significant level ( P value <5 × 10 -8 ) as instrumental variables (IVs) and performed Mendelian randomization (MR) to identify the complications of cholecystectomy. Furthermore, the cholelithiasis was also treated as the exposure to compare its causal effects to those of cholecystectomy, and multivariable MR analysis was carried out to judge whether the effect of cholecystectomy was independent of cholelithiasis. The study was reported based on Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines. RESULTS: The selected IVs explained 1.76% variance of cholecystectomy. Our MR analysis suggested that cholecystectomy cannot elevate the risk of CRC (odds ratio [OR] =1.543, 95% confidence interval [CI]: 0.607-3.924). Also, it was not significant in either colon or rectum cancer. Intriguingly, cholecystectomy might decrease the risk of Crohn's disease (OR = 0.078, 95% CI: 0.016-0.368) and coronary heart disease (OR = 0.352, 95% CI: 0.164-0.756). However, it might increase the risk of irritable bowel syndrome (IBS) (OR = 7.573, 95% CI: 1.096-52.318). Cholelithiasis could increase the risk of CRC in the largest population (OR = 1.041, 95% CI: 1.010-1.073). The multivariable MR analysis suggested that genetic liability to cholelithiasis could increase the risk of CRC in the largest population (OR = 1.061, 95% CI: 1.002-1.125) after adjustment of cholecystectomy. CONCLUSIONS The study indicated that cholecystectomy might not increase the risk of CRC, but such a conclusion needs further proving by clinical equivalence. Additionally, it might increase the risk of IBS, which should be paid attention to in clinical practice.
Humans ; Mendelian Randomization Analysis ; Irritable Bowel Syndrome ; Colorectal Neoplasms/genetics* ; Cholelithiasis/complications* ; Cholecystectomy/adverse effects* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

Nitrate is the main form of inorganic nitrogen that crop absorbs, and nitrate transporter 2 (NRT2) is a high affinity transporter using nitrate as a specific substrate. When the available nitrate is limited, the high affinity transport systems are activated and play an important role in the process of nitrate absorption and transport. Most NRT2 cannot transport nitrates alone and require the assistance of a helper protein belonging to nitrate assimilation related family (NAR2) to complete the absorption or transport of nitrates. Crop nitrogen utilization efficiency is affected by environmental conditions, and there are differences between varieties, so it is of great significance to develop varieties with high nitrogen utilization efficiency. Sorghum bicolor has high stress tolerance and is more efficient in soil nitrogen uptake and utilization. The S. bicolor genome database was scanned to systematically analyze the gene structure, chromosomal localization, physicochemical properties, secondary structure and transmembrane domain, signal peptide and subcellular localization, promoter region cis-acting elements, phylogenetic evolution, single nucleotide polymorphism (SNP) recognition and annotation, and selection pressure of the gene family members. Through bioinformatics analysis, 5 NRT2 gene members (designated as SbNRT2-1a, SbNRT2-1b, SbNRT2-2, SbNRT2-3, and SbNRT2-4) and 2 NAR2 gene members (designated as SbNRT3-1 and SbNRT3-2) were identified, the number of which was less than that of foxtail millet. SbNRT2/3 were distributed on 3 chromosomes, and could be divided into four subfamilies. The genetic structure of the same subfamilies was highly similar. The average value of SbNRT2/3 hydrophilicity was positive, indicating that they were all hydrophobic proteins, whereas α-helix and random coil accounted for more than 70% of the total secondary structure. Subcellular localization occurred on plasma membrane, where SbNRT2 proteins did not contain signal peptides, but SbNRT3 proteins contained signal peptides. Further analysis revealed that the number of transmembrane domains of the SbNRT2s family members was greater than 10, while that of the SbNRT3s were 2. There was a close collinearity between NRT2/3s of S. bicolor and Zea mays. Protein domains analysis showed the presence of MFS_1 and NAR2 protein domains, which supported executing high affinity nitrate transport. Phylogenetic tree analysis showed that SbNRT2/3 were more closely related to those of Z. mays and Setaria italic. Analysis of gene promoter cis-acting elements indicated that the promoter region of SbNRT2/3 had several plant hormones and stress response elements, which might respond to growth and environmental cues. Gene expression heat map showed that SbNRT2-3 and SbNRT3-1 were induced by nitrate in the root and stem, respectively, and SbNRT2-4 and SbNRT2-3 were induced by low nitrogen in the root and stem. Non-synonymous SNP variants were found in SbNRT2-4 and SbNRT2-1a. Selection pressure analysis showed that the SbNRT2/3 were subject to purification and selection during evolution. The expression of SbNRT2/3 gene and the effect of aphid infection were consistent with the expression analysis results of genes in different tissues, and SbNRT2-1b and SbNRT3-1 were significantly expressed in the roots of aphid lines 5-27sug, and the expression levels of SbNRT2-3, SbNRT2-4 and SbNRT3-2 were significantly reduced in sorghum aphid infested leaves. Overall, genome-wide identification, expression and DNA variation analysis of NRT2/3 gene family of Sorghum bicolor provided a basis for elucidating the high efficiency of sorghum in nitrogen utilization.
Nitrate Transporters ; Nitrates/metabolism* ; Sorghum/metabolism* ; Anion Transport Proteins/metabolism* ; Phylogeny ; Protein Sorting Signals/genetics* ; Nitrogen/metabolism* ; DNA ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism*

Objective:To explore the value of digital information line mark coplanar template (also referred to as the line mark template) in 125I radioactive seed implantation for the treatment of lung cancers. Methods:A retrospective analysis was conducted for 58 cases of lung cancers who were treated with template-assisted seed implantation in Oncology Department of the Second Hospital of Tianjin Medical University from Aug 2017 to May 2019.Line mark templates were adopted for 30 cases (the line mark template group) and general standard coplanar templates (also referred to as the general template) were used for 28 cases (the general template group). Pre-plan and post-implant parameters were compared, including the minimum prescription dose delivered to 90% of target volume ( D90), minimum peripheral dose (MPD), mean percentages of volume receiving 100%, 150% and 200% of the prescription doses ( V100, V150 and V200), external index (EI), conformity index (CI), and homogeneity index (HI) of target volume.The operation duration was also compared between the two groups. Results:There was no statistical difference between pre-plan and post-implant D90, MPD, V100, V150 and V200 in the line mark template group ( P>0.05). There was also no statistical difference between pre-plan and post-implant D90, MPD, V100, V150 and V200 of the general template group ( P>0.05). The operation duration of the line mark template group and the general template group was (44.3±12.4) and (60.0±12.8) min, respectively ( t=-3.03, P<0.05). Conclusions:The use of template-assisted seed implantation can accurately achieve preoperative planning, while the line mark template shortens the operation duration and thus improves the tolerance of patients.

Objective:To evaluate the pre- and post-implantation dosimetric consistency and efficacy of CT-guided 125I radioactive seed implantation for the treatment of the local recurrence of lung cancers under the assistance of a universal coplanar template (also referred to as the universal template). Methods:This study involved 38 patients with a local recurrence of non-small cell lung cancers who received universal template-assisted 125I radioactive seed implantation in the Second Hospital of Tianjin Medical University from Jan 2009 to Dec 2015.Preoperative planning was carried out before implantation, and the prescription dose was 110 Gy.The paired T-test was adopted for cooperation between intraoperative verification result and pre-plan values of the dosimetric parameters including minimum peripheral dose (MPD), the minimum prescription doses delivered to 90% and 100% of the target volume ( D90 and D100), conformity index (CI), external index (EI), and homogeneity index (HI). The efficacy was evaluated at the 6th month after implantation according to the RECIST 1.1 (Response Evaluation Criteria in Solid Tumors). Results:All patients successively received the seed implantation.The pre-plan and post-implant dosimetric parameters were as follows: MPD (222.7±26.2), (227.74±29.8) Gy; D90(130.8±13.6), (134.8±12.8) Gy; D100 (106.4±10.6), (110.7±11.8) Gy, CI ( 0.75±0.06), (0.74±0.04), EI(22.7±5.8)%, (24.3±4.8)%; HI(36.8±4.7)%, (37.2±5.3)%, the mean irradiation dose of hearts (19.3±7.2), (21.3±6.8) Gy( P> 0.05). The median follow-up period was 22.5 months (8-98 months). The median survival was 21 months (95% CI, 7.4-34.6), and the 2-year overall survival (OS), progression-free survival (PFS), and local control (LC) rate were 47.4%, 39.5%, and 83.5%, respectively. Conclusions:The universal template-assisted and CT-guided 125I radioactive seed implantation in the treatment of postoperative local recurrence of non-small cell lung cancers can achieve the goal of the preoperative TPS planning during the operation and achieve good efficacy.It is a minimally invasive, accurate, safe and effective therapy.

Objective:To investigate the feasibility, efficacy, and safety of CT- and bronchoscopy-guided 125I seed implantation in the treatment of central lung cancer complicated with atelectasis. Methods:Retrospective analysis was conducted on twenty-nine patients who were treated from May 2016 to Oct 2019 in the Second Hospital of Tianjin Medical University for central non-small-cell lung carcinoma complicated with pulmonary atelectasis that was inoperable due to medical reasons. 125I seeds were implanted into the trachea under the guidance of bronchoscopy first.The 125I seeds were then implanted into the hilum of the lungs by percutaneous puncture under the guidance of the CT and template.The seed activity was 18.5-29.6 MBq, and the prescription dose was 120 Gy.TPS planning and quality verification were performed before and after the operations.The rate of atelectasis recanalization, the satisfactory rate of dose verification, the improvement of dyspnea index, the survival time, and the adverse events during and after operation were observed. Results:All 29 patients with lung cancer complicated with atelectasis successfully completed the seed implantation, and the satisfactory rate of quality verification was 93.1%.The rate of atelectasis recanalization at 2, 6, 12, 18, and 24 months was 93.1%, 89.7%, 78.6%, 76.2%, and 60%, respectively.Their dyspnea and anoxia symptoms were significantly relieved in 5-28 months after treatment.The results showed that the patients′ dyspnea index was 2.8-0.8 before treatment and 1.4-0.9 after treatment.The median follow-up period was 20 months and median survival was 21 months.Adverse events associated with the radiation therapy included pneumothorax, hemoptysis, cough, fever, and particle displacement.No level-3 or more serious adverse events occurred.Conclusions:The CT- and bronchoscopy-guided 125I seed implantation is a safe and effective therapy option for the treatment of central non-small-cell lung carcinoma associated with atelectasis.It contributes to a high rate of local recanalization, and can rapidly improve clinical conditions and quality of life of the patients with few adverse reactions.

Objective To evaluate the clinical efficacy and prognostic factors of limited-stage small cell lung cancer ( LS-SCLC) treated with 125 I radioactive seed implantation guided by CT combined with systemic chemotherapy. Methods A total of 128 limited-stage small cell lung cancer patients were treated with 125 I radioactive seed implantation combined with chemotherapy from Jun 2008 to Jun 2012 in Tianjin Medical University Second Hospital. Theχ2 test was used to analyze the influencing factors of short-term efficacy. Survival rate was calculated by Kaplan-Meier method, single factor analysis was performed by Log-rank, and multivariate analysis was performed by Cox proportional hazard model. Results Totally 128 patients finished the treatment. The overall response rate was 86.7％ ( 111/128 ) after 6 months of treatment. The 1-, 2-and 3-year overall survival rate was 77.9％, 39.8％and 28.0％, respectively, and the median survival time was 21.0 months. The univariate analysis showed that the following factors were main prognostic factors:age, performance status ( PS) , hemoglobin≥120 g/L before treatment, smoking index, the maximum diameter of tumor, neuron-specific enolase before treatment, subscribe for prophylactic cranial irradiation ( PCI) , number of chemotherapy cycle, chemotherapy response, prescribed dose ( PD ) , postoperation dose covering 100％ volume ( D100 ) , remedial model. multivariate analysis revealed that age, PS, hemoglobin≥120 g/L before treatment and PD, the maximum diameter of tumor, number of chemotherapy cycle, chemotherapy response, and remedial model were the independent prognostic factors for survival. 29 patients of 128 suffered from aerothorax and the incidence rate of aerothorax was 27.7％. Totally 16 patients occurred hemoptysis and theincidence rate was 12.5％. Conclusions 125 I radioactive seed implantation therapy showed good effecacy in the treatment of LS-SCLC. Age, PS, hemoglobin≥120 g/L before treatment, the maximum diameter of tumor, number of chemotherapy cycle, chemotherapy response, and remedial model might be the main prognostic factors for LS-SCLC patients.

Objective To investigate the feasibility of reducing CT scanning dose in the process of 125I radioactive seed implantation.Methods GEMS phantom and 062 M phantom were scanned using GE Lightspeed RT large hole CT with 120 kV,100 kV and 80 kV separately,and 150-10 mA (20 mA decreased progressively).The scanning dose,CT value and noise of the region of interest were recorded and the image quality was evaluated.Image signal-to-noise ratio (SNR) and contrast to noise ratio (CNR) values were calculated.Results With the decreasing of tube voltage and current,the SNR values were reduced accorgingly.The values had significant difference with those of standard images except the images acquired with 120 kV,150-70 mA and 100 kV,150-90 mA (t =-9.294-3.717,P ＜0.05).With the decreasing of the tube voltage and current,the CNR decreased significantly.The image quality was too low to evaluate while CNR lower than 2.The high contrast resolution of the CT images were not affected obviously with the tube voltage and current lowering.Conclusions In the process of 125I radioactive seed implantation,it is feasible to choose lower tube voltage and tube current(100 kV,70 mA) to scan the same area repeatedly except for the first scan with standard chest scanning parameters.The patient radiation dose has fallen dramatically.