Abstract Introduction: Tumor size constitutes a very important staging factor among patients afflicted by solid tumors, and was closely associated with the overall survival (OS). Nonetheless, the prognostic import of tumor size in gastric cancer (GC) remains shrouded in uncertainty. Method: A multivariable-adjusted hazard ratio (HR) along with a 95% confidence interval (CI) was computed for GC using Cox proportional hazard regression models. To assess the non-linear association between tumor size and OS, we employed a restricted cubic spline regression analysis. Additionally, a two-piece-wise Cox proportional hazard model was utilized to determine the threshold effect. The efficacy prediction of tumor size was tested by ROC curve. Results: A cohort comprising 2,012 gastric cancer patients who had undergone gastrectomy was included in our secondary analysis, sourced from a multicenter study conducted in Korea. Also, we found a nonlinear association between tumor size and OS at the turning point as 5.7 (95%CI: 5.1, 6.8). The HR for mortality was 1.50 (95%CI: 1.38, 1.64) for tumors size <5.7, while 1.09 (95%CI: 1.05, 1.13) with size ≥ 5.7. There was still a significant non-linear relationship between OS and size after adjusting for potential confounding factors (P=0.001). In addition, Besides, a significantly higher HR was found in young GC patients(≤45: 1.33; 95%CI:1.24, 1.41; >45, 1.16; 95%CI: 1.13,1.19; P for interaction = 0.0004 ). Conclusions: Tumor size was non-linear associated with survival for patients receiving gastrectomy. It might have the higher predictive power in young GC.
The transverse tubule (T-tubule) system is the ultrastructural substrate for excitation-contraction coupling in ventricular myocytes; T-tubule disorganization and loss are linked to decreased contractility in end stage heart failure (HF).We sought to examine (1) whether pathological T-tubule remodeling occurs early in compensated hypertrophy and, if so, how it evolves during the transition from hypertrophy to HF; and (2) the role of junctophilin-2 in T-tubule remodeling.We investigated T-tubule remodeling in relation to ventricular function during HF progression using state-of-the-art confocal imaging of T-tubules in intact hearts, using a thoracic aortic banding rat HF model. We developed a quantitative T-tubule power (TT(power)) index to represent the integrity of T-tubule structure. We found that discrete local loss and global reorganization of the T-tubule system (leftward shift of TT(power) histogram) started early in compensated hypertrophy in left ventricular (LV) myocytes, before LV dysfunction, as detected by echocardiography. With progression from compensated hypertrophy to early and late HF, T-tubule remodeling spread from the LV to the right ventricle, and TT(power) histograms of both ventricles gradually shifted leftward. The mean LV TT(power) showed a strong correlation with ejection fraction and heart weight to body weight ratio. Over the progression to HF, we observed a gradual reduction in the expression of a junctophilin protein (JP-2) implicated in the formation of T-tubule/sarcoplasmic reticulum junctions. Furthermore, we found that JP-2 knockdown by gene silencing reduced T-tubule structure integrity in cultured adult ventricular myocytes.T-tubule remodeling in response to thoracic aortic banding stress begins before echocardiographically detectable LV dysfunction and progresses over the development of overt structural heart disease. LV T-tubule remodeling is closely associated with the severity of cardiac hypertrophy and predicts LV function. Thus, T-tubule remodeling may constitute a key mechanism underlying the transition from compensated hypertrophy to HF.
The application of programmed cell death protein 1 (PD-1) antibodies has brought great benefits to non-small cell lung cancer (NSCLC) patients. Nevertheless, not all patients respond to anti-PD-1 immunotherapy. This study aimed to find response markers to predict efficacy of anti-PD-1 immunotherapy in NSCLC patients. 80 patients with NSCLC who would accept anti-PD-1 immunotherapy were recruited, and peripheral blood was obtained before and after treatment. Flow cytometry was used to detect proportions of circulating cell subsets and expression of co-stimulatory molecules, co-inhibitory molecules and cytokines in T cells from pre- and post-treatment patients. Results showed that proportions of CD4+ and CD8+ T cells, NK, γδT and mucosal-associated invariant T (MAIT) cells were higher and regulatory T cells (Tregs) were lower in responders (n = 50) after treatment but no obvious difference was found in non-responders (n = 30). After treatment, responders showed an increase in the frequency of co-stimulatory and co-inhibitory molecules, as well as the production of cytokines in T cells. This study indicates that monitoring the alterations of immune markers in circulating cells from NSCLC patients may be helpful to discriminate responders and non-responders, which provides a potential novel way to assess efficacy of anti-PD-1 immunotherapy.
Clinical studies have demonstrated the predictive values of changes in electrocardiographic (ECG) parameters for the preexisting myocardial ischemic infarction. However, a simple and early predictor for the subsequent development of myocardial infarction during the ischemic phase is of significant value for the identification of ischemic patients at high risk. The present study was undertaken by using non-human primate model of myocardial ischemic infarction to fulfill this gap. Twenty male Rhesus monkeys at age of 2–3 years old were subjected to left anterior descending artery ligation. This ligation was performed at varying position along the artery so that it produced varying sizes of myocardial infarction at the late stage. The ECG recording was undertaken before the surgical procedure, at 2 h after the ligation, and 8 weeks after the surgery for each animal. The correlation of the changes in the ECG waves in the early or the late stage with the myocardial infarction size was analyzed. The R wave depression and the QT shortening in the early ischemic stage were found to have an inverse correlation with the myocardial infarction size. At the late stage, the R wave depression, the QT prolongation, the QRS score, and the ST segment elevation were all closely correlated with the developed infarction size. The poor R wave progression was identified at both the early ischemic and the late infarction stages. Therefore, the present study using non-human primate model of myocardial ischemic infarction identified the decreases in the R wave and the QT interval as early predictors of myocardial infarction. Validation of these parameters in clinical studies would greatly help identifying patients with myocardial ischemia at high risk for the subsequent development of myocardial infarction.
The primary etiopathology of pediatric OSAHS includes tonsil or adenoid hypertrophy. Severe OSAHS contributes to or aggravates thoracic deformity, which is rarely reported. In the current report, This children sleep snoring more than 4 years, increasing with thoracic severe depression during sleep 2 days. Clinical examination indicated tonsil and adenoid hypertrophy, and polysomnography revealed OSAHS . The symptoms of OSAHS and severe inhalation-related sternum depression disappeared rapidly after tonsillectomy. Our findings indicated that OSAHS were the major causes underlying funnel chest in children. The rarity of the incidence may result in missed diagnosis or misdiagnosis. Polysomnography was recommended for the child diagnosed with funnel chest accompanied by upper airway stenosis.
Abstract Non-human primate monkey model of myocardial ischemic infarction is precious for translational medicine research. Ligation of the left anterior descending (LAD) artery is the effective way to induce myocardial ischemic infarction. However, the consistency of the myocardial infarction thus generated remains problematic. The present study was undertaken to critically evaluate the monkey model of myocardial ischemic infarction to develop a procedure for a consistent cross-studies comparison. Forty male Rhesus monkeys were divided into 4 groups and subjected to LAD artery ligation at different levels along the artery. In addition, the major diagonal branch was selectively ligated parallel to the ligation site of the LAD artery according to the diagonal branch distribution. Analyses of MRI, echocardiography, cardiac hemodynamics, electrocardiography, histopathology, and cardiac injury biomarkers were undertaken to characterize the structural and functional alterations of monkeys with myocardial infarction. Ligation at 40% of the total length of the artery, measured from the apex end, produced variable infarct areas with inconsistent functional alterations. Ligation at 60% or above coupled with selective ligation of diagonal branches produced consistent myocardial infarction with uniformed dysfunction. However, ligation at 70% caused a lethal threat. After a thorough analysis, it is concluded that ligation at 60% of the total length coupled with selective ligation of diagonal branches, which enables standardization of the location of occlusion and the subsequent ischemic area, as well as avoids the influence of the diagonal branches, are ideal to produce a consistent monkey model of myocardial ischemic infarction.
Objective To analyze the effects of-γ-knife treatment with different dosages on level of prolactin (PRL) in patients with different sizes of functional pituitary prolactinomas, and determine an index to guide hormone replacement therapy and the prognosis of -γ-knife treatment in patients with functional pituitary prolactinomas through comparing the changes of tumor sizes and the levels of PRL before and after -γ-knife treatment. Methods A retrospective analysis of the clinical data of 248 patients with functional pituitary prolactinomas was performed; gamma knife treatment was performed on these patients from September 2004 to March 2008. We divided the patients into 3 groups: group Ⅰ (50 Gy≤central dose<60 Gy, 20 Gy＜marginal dose<30 Gy), group Ⅱ (40 Gy≤ central dose＜50 Gy, 15 Gy＜marginal dose<25 Gy) and group Ⅲ (30 Gy ≤ central dose<40 Gy, 12 Gy＜marginal dose<20 Gy). The irradiation dose on optic nerves in the 3 groups was under 9 Gy. Radioimmunoassay was employed to detect the serum PRL level before and 1, 3 and 12 months after γ-knife treatment. The changes of the tumor sizes were observed and compared with cranial MRI 1 and 2 years after -γ-knife treatment.Results Significant differences on the PRL level were noted before -γ-knife treatment between each 2 groups (P<0.05); the PRL level in group Ⅲ was lower as compared with that in group Ⅰ and Ⅱ before γ-knife treatment; however, the PRL level in group Ⅲ was higher as compared with that in group 112 months after -γ-knife treatment; the PRL level in all the 3 groups after γ-knife treatment was significantly lower as compared with that before γ-knife treatment (P<0.05). MRI showed that the tumor had 80% partial response rate (198/248) in the 1st year, 82% complete response rate (203/248) in the 2nd year, increased volume in 19 patients (7.7%) and no change in 26 patients (10.4%). Conclusion Different treatment doses of Gamma knife on functional pituitary prolactinomas has great influences on postoperative recovery of endocrine; the higher doses of the center and edge (especially center), the higher normal rate of postoperative PRL level. Whether it will cause long-term hypopituitarism needs continue follow-up.
Key words:
Prolactinoma; Prolactin; Gamma knife treatment
Myocardial remodeling after ischemic infarction is characterized by collagen accumulation leading to replacement and interstitial fibrosis. Type I and III collagens are predominant components in cardiac fibrosis. Lysyl oxidase (LOX) facilitates the cross-linking of type I and III fibrils, resulting in the formation of stiff fibers and their subsequent tissue deposition. However, the matrix metalloproteinases (MMPs), a family of zinc-dependent enzymes, function in the degradation of the collagen components of extracellular matrix. Tissue inhibitors for MMPs (TIMPs) manipulate the action of MMPs. To understand the contribution of these molecules to cardiac fibrosis, we developed a rhesus monkey model to determine the changes in LOX, MMP1 and TIMP1 in relation to collagen deposition after myocardial ischemic infarction. Male rhesus monkeys were subjected to left anterior descending artery ligation along with sham-operated controls. Histological examination and immunochemistry were performed eight weeks after the ischemic injury. The results showed that both type I and III collagens were increased in the scar area and in the interstitium, and the ratio of type I/III collagens also increased in the scar area but not in the interstitium. The expression of LOX was up-regulated, but the expression of MMP1 was down-regulated in residual myocytes of the scar area and the border zone. The expression of TIMP1 was not changed. The data thus demonstrated that the collagen deposition in infarcted myocardium is correlated with an enhanced cross-linking capacity and a decreased degradation process.
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