Expression of PD-L1 through evolution phase from pre-invasive to invasive lung adenocarcinoma.

BACKGROUND: This study evaluated programmed cell death-ligand 1 (PD-L1) expression from pre-invasive adenocarcinoma to invasive lung adenocarcinoma, aimed to investigate the potential association of PD-L1 pathway with lung adenocarcinoma early evolution. METHODS: We evaluated PD-L1 expression in 1123 resected lung specimens of adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) of stage IA1-IA3. PD-L1 expression was defined based on the proportion of stained tumor cells using the tumor proportion score: < 1% (negative), ≥ 1% (positive) and ≥ 50% (strongly positive). Correlations between PD-L1 expression and T stage, pathological subtype, adenocarcinoma grade, spread through air space (STAS), vascular invasion, lymphatic invasion and driven genes were analyzed. RESULTS: There was almost no PD-L1 expression in AIS or MIA. However, PD-L1 expression was correlated with invasiveness of lung adenocarcinoma. The percentages of PD-L1 positive in IA1-IA3 were 7.22%, 11.29%, and 14.20%, respectively. The strongly positive rates of PD-L1 were 0.38%, 1.64%, and 3.70% in IA1-IA3, respectively. PD-L1 expression and positive rate were also associated with poor pathological subtype and poor biological behavior, such as adenocarcinoma Grade 3, micropapillary or solid dominant subtype, STAS and vascular invasion. Finally, PD-L1 positive rate seems also corrected with driven gene ALK, ROS-1 and KRAS. CONCLUSIONS: PD-L1 expression was positively correlated with the emergence of invasiveness and poor pathological subtype or biological behavior of early-stage lung adenocarcinoma. PD-L1 pathway may be involved in the early evolution of lung adenocarcinoma from AIS to IAC.

[Influence of MRD Status in Newly Diagnosed MM Patients with VGPR and Above after Treatment on Clinical Prognosis].

OBJECTIVE: To investigate the influence of MRD status in newly diagnosed MM patients with VGPR and above after treatment on clinical prognosis. METHODS: Clinical data of 210 newly diagnosed MM patients with VGPR and above after treatment in Fifth People's Hospital of Chendu city. from January 2010 to January 2018 were collected and retrospectively analyzed. The patients were divided into 2 groups: group A (152 patients with MRD-) and group B (58 patients with MRD+). The influencing factors of progression free survival and overall survival of patients were analyzed, and the correlation between MRD status and high-risk cytogenetic abnormalities, treatment plan and response to treatment were evaluated. RESULTS: There were no significant difference in clinical characteristics between the patients in 2 groups (P＞0.05). Single factor analysis showed that ASCT and MRD status were related with progression free survival of patients with newly diagnosed MM (P＜0.05). Multivariate analysis by Cox regression model showed that MRD+ persistence was the independent risk factor for progression free survival of patients with newly diagnosed MM (P＜0.05). The cumulative progression free survival rate in 2-year with follow-up of patients in group A was significantly higher than that in B group (P＜0.05). The median progression free survival time and overall survival time of patients with persistent MRD- were significantly longer than those of MRD+ (P＜0.05). The single factor analysis showed that MRD- maintenance time was the influencing factor of PFS and OS time of newly diagnosed MM patients (P＜0.05). The cumulative overall survival rate in 2-year with follow-up of patients with MRD- maintenance for 6 months was significantly higher than that of patients with MRD- maintenance for＜6 months (P＜0.05). The cumulative progression free survival rate and overall survival rate in 2 years with follow-up of patients with MRD- maintenance for ≥12 months were significantly higher than those of MRD-maintenance for ＜12 months（P＜0.05）. The median progression free survival time of patients with MRD- was significantly longer than that of patients with MRD+ who had≥ one kind of high-risk cytogenetic abnormality (P＜0.05). The MRD- rate of patients received ASCT was significantly higher than that of patients without ASCT (P＜0.05). The median progression free survival time of patients with MRD- was significantly longer than that of patients with MRD+ (P＜0.05). The maintenance time of MRD- in patients with bortezomib treatment was significantly longer than that of patients without bortezomib treatment in population with MRD- (P＜0.05). The median progression free survival time of patients with bortezomib treatment was significantly longer than patients without bortezomib treatment (P＜0.05). CONCLUSION: MRD+ maintenance in newly diagnosed MM patients with VGPR and above after treatment closely relates with poor long-term prognosis, however, the MRD- maintenance time can be used for prognosis evaluation. MRD+ suggests that patients possess the possibility of early recurrence, and dynamic monitoring of MRD status in treatment can be helpful to clinical determination of treatment opportunity for relapsed MM patients.

A model of injury potential for myelinated nerve fiber.

Excellent models have been described in literatures which related membrane potential to extracellular electric or magnetic stimulation and which described the formation and propagation of action potentials along the axon, for both myelinated and nonmyelinated fibers. There is not, however, an adequate model for nerve injury which allows to compute the distribution of injury potential, a direct current potential difference between intact and injured nerve, because its importance has been ignored in the shadow of the well-known action potential. This paper focus on the injury potential and presents a model of the electrical properties of myelinated nerve which describes the time course of events following injury. The time-varying current and potential at all nodes can be computed from the model, and the factors relate to the amplitude of injury potential can be determined. It is shown that the amplitude of injury potential decreased gradually with injury time, and the recession curve was exponential. Results also showed that the initial amplitude of injury potential is positively related to the grade of injury and fiber diameter. This model explained the mechanism of formation of injury potential and can provide instruction for applied electric field to prevent the formation injury potential.

Injury potentials of spinal cord in ex vivo compression injury model.

The effect of applied electric field on neuroprotection and axonal regeneration has been studied in previous studies of acute spinal cord injury (SCI). However, due to the complexity of the microenvironment of the lesion site, the underlying mechanism of applied electric field is not yet fully understood. Thus, the injury potential, a significant index of the microenvironment change, was investigated in ex vivo spinal cords compression injury. Spinal cords isolated from rat were cultured in a double sucrose gap recording chamber. Both compound action potential (CAP) and injury potential were measured. Compression induced the decreasement of compound action potential, but the amplitude of CAP increased gradually after decompression. Compression also lead to the appearance of injury potential, represented by the voltage difference between the gap potential before and after compression, and the injury potential decreased with time logarithmicly after decompression. Intracellular Na(+) and Ca(2+) concentrations were measured and results showed that after injury these ions flowed into intracellular space. Therefore, the current approach can provide a basis for investigating the formation mechanism of the injury potential and help understand the pathophysiology of the SCI.

Chaotic extension neural network theory-based XXY stage collision fault detection using a single accelerometer sensor.

The collision fault detection of a XXY stage is proposed for the first time in this paper. The stage characteristic signals are extracted and imported into the master and slave chaos error systems by signal filtering from the vibratory magnitude of the stage. The trajectory diagram is made from the chaos synchronization dynamic error signals E1 and E2. The distance between characteristic positive and negative centers of gravity, as well as the maximum and minimum distances of trajectory diagram, are captured as the characteristics of fault recognition by observing the variation in various signal trajectory diagrams. The matter-element model of normal status and collision status is built by an extension neural network. The correlation grade of various fault statuses of the XXY stage was calculated for diagnosis. The dSPACE is used for real-time analysis of stage fault status with an accelerometer sensor. Three stage fault statuses are detected in this study, including normal status, Y collision fault and X collision fault. It is shown that the scheme can have at least 75% diagnosis rate for collision faults of the XXY stage. As a result, the fault diagnosis system can be implemented using just one sensor, and consequently the hardware cost is significantly reduced.

The effects of chronic repetitive transcranial magnetic stimulation on glutamate and gamma-aminobutyric acid in rat brain.

Recent studies have shown that repetitive transcranial magnetic stimulation (rTMS) has therapeutic potential for some neurological and psychiatric disorders. However, the neurobiological effects of this tool are not sufficiently explained so far, previous research reported that rTMS can change dopamine release, there have been few studies to examine a possible effect of rTMS on amino acid neurotransmitter. This study aimed to determine the effects of chronic rTMS on glutamate and gamma-aminobutyric acid concentration in the rat brain. Sprague­Dawley rat was subject to 500 pulses of 0.5 Hz rTMS for 15 days, or sham stimulation. After last stimulation, glutamate and gamma-aminobutyric acid content were measured by high performance liquid chromatography (HPLC). Results showed that the content of glutamate and gamma-aminobutyric acid increased significantly in hippocampus and striatum after chronic rTMS, but reduced significantly in the hypothalamus. These results indicate that chronic rTMS has a modulatory effect on the glutamate and gamma-aminobutyric acid systems. This change in amino acid neurotransmitter may contribute to its beneficial effects.