In patients with fully resected postoperative pathologically confirmed stage IIIA-N2 NSCLC and high risk of cerebral metastases after adjuvant chemotherapy, PCI prolongs DFS and decreases the incidence of brain metastases.

BackgroundThe human SLC25A13 gene encodes citrin, the liver-type mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), and SLC25A13 mutations cause citrin deficiency (CD), a disease entity that encompasses different age-dependant clinical phenotypes such as Adult-onset Citrullinemia Type II (CTLN2) and Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD). The analyses of SLC25A13 gene and its protein/mRNA products remain reliable tools for the definitive diagnoses of CD patients, and so far, the SLC25A13 mutation spectrum in Chinese CD patients has not been well-characterized yet.Methods and ResultsBy means of direct DNA sequencing, cDNA cloning and SNP analyses, 16 novel pathogenic mutations, including 9 missense, 4 nonsense, 1 splice-site, 1 deletion and 1 large transposal insertion IVS4ins6kb (GenBank accession number KF425758), were identified in CTLN2 or NICCD patients from China, Japan and Malaysia, respectively, making the SLC25A13 variations worldwide reach the total number of 81. A large NICCD cohort of 116 Chinese cases was also established, and the 4 high-frequency mutations contributed a much larger proportion of the mutated alleles in the patients from south China than in those from the north (χ2 = 14.93, P<0.01), with the latitude of 30°N as the geographic dividing line in mainland China.ConclusionsThis paper further enriched the SLC25A13 variation spectrum worldwide, and formed a substantial contribution to the in-depth understanding of the genotypic feature of Chinese CD patients.

Background: Many studies have shown the prognostic value of inflammation based factors in different cancers. This work aimed to explore the prognostic value of pretreatment C-reactive protein/albumin (CRP/Alb) ratio in patients with cervical cancer, and compared to other inflammatory prognostic factors, such as neutrophil/lymphocyte ratio(NLR), Glasgow prognostic score (mGPS), prognostic index (PI), platelet/lymphocyte ratio (PLR), prognostic nutritional index (PNI), clinicopathological parameter and squamous cell carcinoma antigen (SCC-Ag).Methods: This study was a retrospective analysis of the data related to 229 patients with newly diagnosed cervical cancer. The potential prognostic factors were evaluated by univariate and multivariate survival analysis. The correlation between CRP/Alb ratio and other prognostic factors were analyzed by Chi-Square or Fisher's exact test.Results: Multivariate analyses showed that CRP/Alb ratio was an independent predictor of overall survival (OS) in cervical squamous cell carcinoma (SCC) (HR, hazard ratio = 2.529; p = 0.045), but not in all cases of cervical cancer. However, NLR was a prognostic factor in the whole cervical cancer (HR = 2.47; p = 0.020) as well as in SCC subgroup (HR = 2.28; p = 0.038). Spearman's rank correlation analysis revealed that NLR showed a positive correlation with CRP/Alb ratio (p < 0.001). The combined index of NLR and CRP/Alb ratio could enhance the prognostic value compared to NLR or CRP/Alb ratio alone. Moreover, a high CRP/Alb ratio > 0.022 was associated with older patients (p < 0.001) and more advanced International Federation of Gynecology and Obstetrics (FIGO) stages (p < 0.001). In addition, NLR and CRP/Alb ratio were associated with SCC-Ag concentration in SCC. Furthermore, CRP/Alb ratio was a superior prognosis factor than mGPS, PI, PLR and PNI in SCC. Moreover, positive correlation was present among SCC-Ag, NLR and CRP/Alb ratio.Conclusions: CRP/Alb ratio might be considered as a novel prognosis factor and combined with NLR could improve the accuracy of OS prediction in patients with cervical cancer as well as its most common histological SCC subtypes.

Recent studies have indicated that inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS), modified GPS (mGPS) and C-reactive protein/Albumin (CRP/Alb) ratio, platelet–lymphocyte ratio (PLR), and neutrophil–lymphocyte ratio (NLR), have been reported to have prognostic value in patients with many types of cancer, including nasopharyngeal carcinoma (NPC). In this study, we proposed a novel inflammation-based stage, named I stage, for patients with NPC. A retrospective study of 409 newly-diagnosed cases of NPC was conducted. The prognostic factors (GPS, mGPS, CRP/Alb ratios, PLR, and NLR) were evaluated using univariate and multivariate analyses. Then, according to the results of the multivariate analyses, we proposed a I stage combination of independent risk factors (CRP/Alb ratio and PLR). The I stage was calculated as follows: patients with high levels of CRP/Alb ratio (>0.03) and PLR (>146.2) were defined as I2; patients with one or no abnormal values were defined as I1 or I0, respectively. The relationships between the I stage and clinicopathological variables and overall survival (OS) were evaluated. In addition, the discriminatory ability of the I stage with other inflammation-based prognostic scores was assessed using the AUCs (areas under the curves) analyzed by receiver operating characteristics (ROC) curves. The p value of <0.05 was considered to be significant. A total of 409 patients with NPC were enrolled in this study. Multivariate analyses revealed that only the CRP/Alb ratio (Hazard ratio (HR) = 2.093; 95% Confidence interval (CI): 1.222–3.587; p = 0.007) and PLR (HR: 2.003; 95% CI: 1.177–3.410; p = 0.010) were independent prognostic factors in patients with NPC. The five-year overall survival rates for patients with I0, I1, and I2 were 92.1% ± 2.9%, 83.3% ± 2.6%, and 63.1% ± 4.6%, respectively (p < 0.001). The I stage had a higher area under the curve value (0.670) compared with other systemic inflammation-based prognostic scores (p < 0.001). The I stage is a novel and useful predictive factor for OS in patients with NPC.

The lower cervical pedicle size differs between the Chinese and the non-Chinese population. Knowledge of pedicle dimensions and surface landmarks is crucial for the safe placement of screws, but few quantitative data concerning the lower cervical pedicle using CT scan and multiplanar reformations (MPR) in a Chinese population exist. The aim of this study was to evaluate lower cervical pedicle (C3-C7) dimensions in a Chinese population by computed axial tomography for surgical application. The dimensions of the pedicles (C3-C7) were determined in 60 patients from CT images of cervical spinal lesions. Measurements of pedicle height, width, pedicle axis length, effective length, and two angles of the pedicles, the distances from the projection point of the pedicle axis to the lateral edge of the lateral mass and to the inferior edge of the superior facet were measured. The smallest outer pedicle width was found at C3 among the female and C4 among the male. This measurement was significantly different between male and female patients in the outer pedicle width (P < 0.05; independent samples t test) at C3 and C4. The mean values of the outer pedicle width ranged from 5.4 to 6.7 mm in males, and 4.4 to 6.3 mm in females. The projection point of the pedicle axis in the lateral-superior area of the cervical lateral mass was the most important. There were significant correlations (P < 0.01; Kendall's W test) between the vertebral level and both pedicle angles (PTA and PSA). The smallest pedicle transverse angle was at C7 in males and females. The cervical spinal cord or vertebral artery may be at risk of injury if the angulation of the screw insert is over-medial or over-lateral in the transverse plane. Therefore, preoperative CT evaluation of pedicle transverse angle is very important. Considering the amount of variation among individuals, our data on CT measurements of pedicle in a Chinese population in conjunction with evaluation of the results of preoperative CT may enhance the safety of transpedicular screw fixation in the lower cervical spine.

There is accumulating evidence that autoimmunity to insulin B chain peptide, amino acids 9–23 (insulin B:9–23), is central to development of autoimmune diabetes of the NOD mouse model. We hypothesized that enhanced susceptibility to autoimmune diabetes is the result of targeting of insulin by a T-cell receptor (TCR) sequence commonly encoded in the germline. In this study, we aimed to demonstrate that a particular Vα gene TRAV5D-4 with multiple junction sequences is sufficient to induce anti-islet autoimmunity by studying retrogenic mouse lines expressing α-chains with different Vα TRAV genes. Retrogenic NOD strains expressing Vα TRAV5D-4 α-chains with many different complementarity determining region (CDR) 3 sequences, even those derived from TCRs recognizing islet-irrelevant molecules, developed anti-insulin autoimmunity. Induction of insulin autoantibodies by TRAV5D-4 α-chains was abrogated by the mutation of insulin peptide B:9–23 or that of two amino acid residues in CDR1 and 2 of the TRAV5D-4. TRAV13–1, the human ortholog of murine TRAV5D-4, was also capable of inducing in vivo anti-insulin autoimmunity when combined with different murine CDR3 sequences. Targeting primary autoantigenic peptides by simple germline-encoded TCR motifs may underlie enhanced susceptibility to the development of autoimmune diabetes.

The level of anine aminotransferase/aspartate aminotransferase (ALT/AST) ratio in the serum was often used to assess liver injury. Whether the ALT/AST ratio (LSR) was associated with prognosis for gastric adenocarcinoma (GA) has not been reported in the literature. Our aim was to investigate the prognostic value of the preoperative LSR in patients with GA. A retrospective study was performed in 231 patients with GA undergoing curative resection. The medical records collected include clinical information and laboratory results. We investigated the correlations between the preoperative LSR and overall survival (OS). Survival analysis was conducted with the Kaplan–Meier method, and Cox regression analysis was used to determine significant independent prognostic factors for predicting survival. A p value of <0.05 was considered to be statistically significant. A total of 231 patients were finally enrolled. The median overall survival was 47 months. Multivariate analysis indicated that preoperative LSR was an independent prognostic factor in GA. Patients with LSR ≤ 0.80 had a greater risk of death than those with LSR > 0.80. The LSR was independently associated with OS in patients with GA (hazard ratio: 0.610; 95% confidence interval: 0.388–0.958; p = 0.032), along with tumor stages (hazard ratio: 3.118; 95% confidence interval: 2.044–4.756; p < 0.001) and distant metastases (hazard ratio: 1.957; 95% confidence interval: 1.119–3.422; p = 0.019). Our study first established a connection between the preoperative LSR and patients undergoing curative resection for GA, suggesting that LSR was a simple, inexpensive, and easily measurable marker as a prognostic factor, and may help to identify high-risk patients for treatment decisions.

Purpose: This study aimed to develop an effective nomogram for predicting survival in surgically treated non-small cell lung cancer patients.Methods: We retrospectively evaluated 856 NSCLC in this study. Cox regression analyses were performed to identify significant prognostic factors for developing a nomogram to predict overall survival (OS). The discriminative ability was assessed with the concordance index (C-index).Results: On multivariate analysis of the 856 cohort, independent factors for survival were CRP, fibrinogen, tumor status, nodal status, distant metastasis and clinical stage, which were entered into the nomogram. The C-index of the established nomogram 0.720 (95% CI: 0.671-0.769) was higher than that of the seventh edition TNM staging system 0.689 (95% CI: 0.668-0.709) for predicting OS (P < 0.05). Compared with patients with low CRP levels (< 8.6 g/L) and low fibrinogen levels (< 3.7 g/L), patients with high CRP and fibrinogen levels had shorter OS. Subgroup analyses revealed that the nomogram was a favorable prognostic parameter in stage I-IV NSCLC (P < 0.05).Conclusion: A nomogram integrating CRP and fibrinogen, which could be convenient and feasible to obtain from the serum preoperatively, may assist in risk stratification for individual patient with resected NSCLC.