Neuroprotective effects of voluntary exercise and Yisaipu after traumatic brain injury in mice.

The mechanisms underlying exercise-induced neuroprotective effects after traumatic brain injury (TBI) remained elusive, and there is a lack of effective treatments for TBI. In this study, we investigated the effects of an integrative approach of exercise and Yisaipu (TNFR-IgG fusion protein, TNF inhibitor) in a mouse TBI model. Male C57BL/6J mice were randomly assigned to a sedentary group or a group that followed a voluntary exercise regimen. The effects of 6-week prophylactic preconditioning exercise (PE) alone or in combination with post-TBI Yisaipu treatment on moderate TBI associated deficits were examined. The results showed that combined treatments of PE and post-TBI Yisaipu were superior to single treatments on reducing sensorimotor and gait dysfunctions in mice. These functional improvements were accompanied by reduced systemic inflammation largely via decreased serum TNF-α, boosted autophagic flux, and mitigated lesion volume after TBI. Given these neuroprotective effects, composite approaches such as a combination of exercise and TNF inhibitor may be a promising strategy for facilitating functional recovery from TBI and are worth further investigation.

Evaluating the adequacy of nodal status in node-negative gallbladder cancer with T1b-T2 stages: use of nodal staging score.

BACKGROUND: The study aimed at establishing a nodal staging score (NSS) to quantify the likelihood that pathologic node-negative gallbladder cancer (GBC) patients are indeed free of lymph node (LN) metastasis. METHODS: Clinicopathological data of 1374 GBC patients with T1b-T2 stages were collected from the Surveillance, Epidemiology and End Result database (design cohort [DC], n = 1289) and the First Affiliated Hospital of Sun Yat-sen University (validation cohort [VC], n = 85). NSS was derived from the count of examined LNs (ELNs) and T stage by using a beta-binomial model, and represented the probability that a node-negative patient is correctly staged. The prognostic value of NSS in node-negative GBC was evaluated by survival analysis. RESULTS: The probability of missing a nodal disease in node-negative GBC patients with T1b-T2 stages (pT1bN0 and pT2N0) decreased as the number of ELNs increased. NSS increased as the number of ELNs increased. For pT1bN0 and pT2N0 patients, examination of 5 and 27 lymph nodes could ensure an NSS of 90.0%, respectively. Multivariate analysis revealed that NSS was an independent predictor for overall survival in pT1bN0 and pT2N0 GBC patients (DC, HR:0.53, 95%CI: 0.42-0.66, p < 0.001; VC, HR: 0.33, 95%CI: 0.14-0.76, p = 0.009). CONCLUSION: NSS could evaluate the adequacy of nodal staging and predict the prognosis in pT1bN0 and pT2N0 GBC patients, and hence was helpful to guide their treatment strategies.

Development and validation of a nomogram for predicting overall survival of node-negative ampullary carcinoma.

BACKGROUND: The accuracy of the current staging system for predicting the overall survival (OS) of patients with ampullary carcinoma (AC) is still unsatisfactory, especially in node-negative (N0) patients. We aimed at establishing a nomogram to accurately predict OS in N0 AC. METHODS: This study enrolled 697 N0 AC patients from the Surveillance, Epidemiology, and End Results database (design cohort [DC], n = 697) and the First Affiliated Hospital of Sun Yat-sen University (validation cohort [VC], n = 112), who underwent surgical resection. The nomogram was established by using prognostic factors determined by univariate and multivariate regression analyses. RESULTS: The nomogram for OS was developed by using four independent prognostic factors, including age, grade, T stage, and a number of examined lymph nodes. The C-index of a nomogram for OS in DC and VC was 0.665 and 0.731, respectively. Calibration curves showed good consistency of the nomogram. The nomogram had a better accuracy in predicting OS compared with conventional staging system (P < .05). On the basis of nomogram-predicted scores, the patients were stratified into groups with different risk. The OS of low-risk patients was significantly longer than high-risk ones (P ≤ .010). CONCLUSIONS: The nomogram could be used to predict the OS of N0 AC. It could help guide further treatment in clinical practice.

Establishment and validation of a nomogram for predicting overall survival of node-negative perihilar cholangiocarcinoma.

AIM: There lacks a predictive model for overall survival (OS) of node-negative perihilar cholangiocarcinoma (PHC). This study aimed at developing and validating a prognostic nomogram to predict OS of node-negative PHC after resection. METHODS: We established a nomogram via multivariate regression analysis by using the design cohort (n = 410, obtained from Surveillance, Epidemiology, and End Results database), and its external verification was done in the validation cohort (n = 100, the First Affiliated Hospital of Sun Yat-sen University). Predictive accuracy of the nomogram was assessed by concordance-index (C-index), calibration curves, and decision curve analysis (DCA). Performance of the nomogram was compared with the American Joint Committee on Cancer (AJCC) staging system. RESULTS: Multivariate regression analysis revealed that age, tumor grade, and the count of examined lymph nodes were independent prognostic factors for OS of node-negative PHC. The nomogram had a C-index of 0.603 and 0.626 in design cohort and validation cohort, respectively, which was better than that of AJCC staging system (both p < 0.05). The calibration curves showed good consistency between actual and nomogram-predicted OS probabilities. DCA showed that nomogram had better clinical usefulness. Furthermore, the nomogram-predicted scores could stratify the patients into three risk groups, and patients in higher risk group had worse prognosis than those in lower risk group (all p < 0.05). CONCLUSION: The proposed nomogram had a better prognostic accuracy than the AJCC staging system in predicting postoperative OS of node-negative PHC. It was helpful to guide the adjuvant therapeutic strategies for node-negative PHC.