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.

TIM-3 gene is highly expressed in ephithelial ovarian cancer to promote proliferation and migration of ovarian cancer cells / 南方医科大学学报

OBJECTIVE@#To analyze the expression of immunoglobulin mucin molecule 3 (TIM-3) in epithelial ovarian cancer (EOC) and the effects of TIM-3 knockdown and overexpression on proliferation and migration of ovarian cancer cells.@*METHODS@#We analyzed TIM-3 expression in EOC and normal ovarian tissues using GEPIA database. We also detected TIM-3 expression levels in 82 surgical specimens of EOC and 18 specimens of normal ovarian tissues using immunohistochemistry, and analyzed the correlation of TIM-3 expression with clinicopathological parameters and survival outcomes of the patients. The expression of TIM-3 and Wnt1 mRNA in the tissues were detected using qRT-PCR. We constructed SKOV3 cell models of TIM-3 knockdown and overexpression and examined the changes in proliferation, apoptosis, migration and invasion of the cells using MTT assay, Annexin V-FITC/PI staining, scratch test and Transwell assay. The activity of Wnt/β-catenin pathway in the transfected was detected using dual luciferase reporter assay, and the mRNA levels of TCF-7, TCCFL-2 and CD44 were detected using qPCR. The protein expressions of MMP-9, CD44, Wnt1, β-catenin and E-cad in the transfected cells were detected with Western blotting.@*RESULTS@#The positive expression rate of TIM-3 was significantly higher in EOC tissues than in normal ovarian tissues (P < 0.05). The expression of TIM-3 was significantly correlated with FIGO stage, histological differentiation and lymph node metastasis, and was positively correlated with Wnt1 level (P < 0.05). In SKOV3 cells, TIM-3 knockdown significantly lowered the activity of Wnt/ β-catenin pathway, inhibited cell proliferation, migration and invasion, and promoted cell apoptosis. TIM-3 knockdown significantly down-regulated the mRNA levels of TCF-7, TCFL-2 and CD44 and the protein levels of MMP-9, CD44, Wnt1 and β-catenin, and significantly up-regulated the expression level of E-cad (P < 0.05). Overexpression of TIM-3 caused opposite effects in SKOV3 cells.@*CONCLUSION@#TIM-3 is highly expressed in EOC tissue to promote malignant behaviors of the tumor cells possibly by activating the Wnt/β-catenin signal pathway.

[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.

Prognostic analysis of plantar fasciitis treated by pneumatic ballistic extracorporeal shock wave versus ultrasound guided intervention / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the medium- and long-term effect of pneumatic ballistic extracorporeal shock wave versus ultrasound-guided hormone injection in the treatment of plantar fasciitis.</p><p><b>METHODS</b>The clinical data were collected from patients with plantar fasciitis admitted to PLA General Hospital pain department from September, 2015 to February, 2017. The patients were randomly divided into ultrasound-guided drug injection group and shock wave group. The therapeutic parameters including the numerical rating scale (NRS) scores in the first step pain in the morning, American Orthopedic Foot and Ankle Society (AOFAS) Ankle Hindfoot Scale, and thickness of the plantar fascia were monitored before and at 1 week, 1 month, 3 months, and 6 months after the treatment. The recurrence rate, effectiveness, and patient satisfaction were compared between the two groups at 6 months after the treatment.</p><p><b>RESULTS</b>Thirty-nine patients were enrolled in shock wave group and 38 patients in ultrasound group. The NRS scores in the first step pain in the morning were lowered after treatment in both groups (P<0.05), and the scores were significantly lower in ultrasound group than in shock wave group at 1 week and 1 month (P<0.01), but significantly higher in ultrasound group than in shock wave group at 3 and 6 months after treatment (P<0.05). The AOFAS functional scores were increased in both groups (P<0.05) at 6 months after treatment, was significantly lower in ultrasound group than in shock wave group than group B (90.44∓13.27 vs 75.76∓21.40; P<0.05). The effective rates in shock wave group and ultrasound group were 92.31% and 76.32%, respectively (P<0.05). Recurrence was found in 1 patient (2.56%) in shock wave group and in 8 (21.05%) in ultrasound group (P<0.05). The patient satisfaction scores were significantly higher in shock wave group than in ultrasound group (8.13∓2.67 vs 6.63∓3.75, P=0.048).</p><p><b>CONCLUSION</b>Pneumatic ballistic extracorporeal shock achieves better medium- and long-term outcomes than ultrasound-guided hormone injection in the treatment of plantar fasciitis.</p>

The sustained release effect of ropivacaine loading poly (lactic acid co castor oil) microspheres for sciatic nerve block in mice / 解放军医学杂志

Objective To investigate the efficacy ofpoly (lactic acid co castor oil) microspheres containing ropivacaine for sciatic nerve block of mice.Methods A total of 150 Kunming male mice were randomly assigned into 3 groups,namely placebo microspheres (lactic acid co castor oil) group (group A,n=50),ropivacaine injection group (group B,n=50) and ropivacaine microspheres group (group C,n=50).After sevoflurane anesthesia,the mouse was fixed on the operating table and the bilateral sciatic nerve was exposed.The corresponding preparations were implanted or injected near the sciatic nerve.Five mice were randomly selected from each group for the next experiments.Paw withdrawal thermal latency,the ability to splay and flex of the hind paw and plasma ropivacaine concentration were measured 10min,30min,1h,3h,5h,7h,10h,15h,30h and 48h after drug administration.Results The anesthetic effect of group C began to work at 3h.Compared with group B,the duration of sciatic nerve sensory block of group C was significantly longer and the effect of motor block was weaker.No anesthetic effect was observed in group A.The sensory and motor block of group B reached the peak at 1h,and the pharmacodynamics subsided at 7h.Compared with group B,the concentration of ropivacaine in group C increased slowly,and the peak value at 10h after administration was gradually decreased.Conclusions Ropivacaine loading poly (lactic acid co castor oil) microspheres can significantly extend the effect of ropivacaine on sciatic nerve sensory block.Compared with ropivacaine injection,motor block effect of ropivacaine loading poly (lactic acid co castor oil) microspheres is reduced and its plasma ropivacaine concentration fluctuation range is small.

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.

The effect of low frequency transcranial magnetic stimulation on neuropeptide-Y expression and apoptosis of hippocampus neurons in epilepsy rats induced by pilocarpine / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the effect of low frequency transcranial magnetic stimulation (LF-TMS) on changing neuropeptide-Y (NPY) expression and apoptosis of hippocampus neurons in epilepsy rats induced by pilocarpine (PLO).</p><p><b>METHODS</b>Thirty male Sprague Dawley rats (240 g +/- 20 g) were randomly divided into 2 groups. I group simply celiac injected pilocarpine. II group celiac injected PLO after LF-TMS. Pathological item included HE staining, NPY immunohistochemical staining and apoptosis staining.</p><p><b>RESULTS</b>HE staining revealed neurons of hippocampus were obviously death and cell's structure was destroyed in PLO group. The PLO + LF-TMS group was less injured and destroyed. Using One-Way ANOVA, NPY immunohistochemical staining shown the positive cell number was increased at all areas of hippocampus in PLO group contrasting with the low positive cell number in the PLO + LF-TMS group. In PLO group the number of apoptosis cell at hippocampus areas was significant higher than the PLO + LF-TMS group.</p><p><b>CONCLUSIONS</b>Using the PLO evoked epilepsy model, LF-TMS alleviated neurons injury at hippocampus area, so LF-TMS might playing an important role in resisting the progressing of epilepsy. The positive cell number of NPY increased at all areas of hippocampus, which indicated the close relation between NPY and epilepsy. NPY might have some function on resisting epilepsy.</p>

Effects of extremely low frequency pulsed electromagnetic field on different-derived osteoblast-like cells / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect of the extremely low frequency pulsed electromagnetic field (PEMF) on the proliferation and differentiation of osteoblast-like cells.</p><p><b>METHODS</b>The MC3T3-E1 cell and the primary osteoblast cell derived from 2-day-old Sprague Dawley (SD) rat calvaria were exposed to PEMF with a magnetic flux density of 1.55 mT at 48 Hz for 24 or 48 h. MTS was applied to analyze cell proliferation and flow cytometry to detect cell cycle. The intracellular alkaline phosphatase (ALP) activity was measured by colorimetry.</p><p><b>RESULTS</b>PEMF of 1.55 mT at 48 Hz decreased significantly the cell percentage of S or G(2)M phase (P < 0.05), but did not affect cell number of MC3T3-E1 cells. Although the number of the primary osteoblast cells did not alter by MTS assay after exposure to PEMF for 24 h continuously, the cell percentage of G(2)M phase increased significantly (P < 0.01). When the culture time extended to 48 h, the cell number increased greatly (P < 0.01) and the cell percentage of G(2)M phase decreased significantly despite of the exposure type (P < 0.01). After the primary osteoblast cells were exposed to PEMF for 24 h continuously, the ALP activity decreased significantly (P < 0.05), whereas it increased significantly after exposure to PEMF for 48 h continuously (P < 0.05).</p><p><b>CONCLUSION</b>PEMF of 1.55 mT at 48 Hz does not affect proliferation and differentiation of MC3T3-E1 cell, but it promotes proliferation of primary osteoblast cell, inhibits differentiation at proliferation stage and promotes differentiation at differentiation stage of primary osteoblast cell.</p>

The design of a transcranial magnetic stimulation (TMS) system and its implementation / 中国医疗器械杂志

Transcranial magnetic stimulation (TMS) is a non-invasive diagnostic and therapeutic technigue. This paper expounds the design and manufacture of the TMS system, which meets all the requirements of the TMS study and clinical diagnosis and treatments.

Effects of low frequency pulsed magnetic field on the proliferation and differentiation of HepG2 cells / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the effects of low frequency pulsed magnetic field on the proliferation and differentiation of HepG2 cells.</p><p><b>METHODS</b>3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) colorimetry method and ELISA assay of alpha-fetoprotein (AFP) were used to determine the cell proliferation and differentiation after the cells were exposed to pulsed magnetic fields with different frequency but the same field intensity.</p><p><b>RESULTS</b>There were no significant differences in cell proliferation between sham and treated groups exposed to the field of 80 Hz, 1.55 mT for 1, 4, 8, 12, 24 h (P > 0.05). There were also no significant differences in cell proliferation and AFP secretion between sham and treated groups exposed to 16 Hz, 1.55 mT pulsed magnetic fields for 1, 4, 8, 24 h (P > 0.05).</p><p><b>CONCLUSION</b>There were no "window effects" found in HepG2 cells proliferation or AFP secretion at 16 Hz and 80 Hz pulsed magnetic fields.</p>

Effect of extremely low frequency magnetic fields on intracellular free calcium in HepG2 cells / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the effect of extremely low frequency magnetic fields on intracellular calcium concentration ([Ca(2+)]i).</p><p><b>METHODS</b>Fura-2 loaded HepG2 cells were exposed to 1.55 mT (average value), 16 Hz pulsed magnetic fields for 60 min and to 300 mT, 2 Hz rotating magnetic fields for 5 min, and then [Ca(2+)]i was measured by fluorescence spectrophotometer. [Ca(2+)]i of HepG2 cells was also measured when they were exposed to 0.9 mT [root mean square (rms)], 16 Hz sinusoidal magnetic fields in real time.</p><p><b>RESULTS</b>The R values (F(340) nm/F(380) nm) of the control and the exposed group were 2.4519 +/- 0.2378 and 2.5266 +/- 0.2915 respectively after HepG2 cells were exposed to 1.55 mT, 16 Hz magnetic fields, 1.365 0 +/- 0.0626 and 1.3602 +/- 0.0771 respectively to 300 mT, 2 Hz rotating magnetic fields. The ratios of the trendline slope [r((501 - 1,000)) / r((0 - 500))] from the data of R values were 1.1213 +/- 0.4559 and 1.0727 +/- 0.1971 respectively (P > 0.05), and the ratios of the intercept [b((501 - 1,000)) / b((0 - 500))] from the trendline were 0.9912 +/- 0.0098 and 0.9979 +/- 0.0060 (P > 0.05) when HepG2 cells were exposed to the 0.9 mT, 16 Hz sinusoidal magnetic fields.</p><p><b>CONCLUSION</b>The effect of extremely low frequency magnetic fields on [Ca(2+)]i of HepG2 cells under the experimental condition has not been found.</p>

Low frequency transcranial magnetic stimulation changes seizure and neuropeptide Y expression of hippocampal neurons in rats epilepsy induced by pilocarpine / 中华物理医学与康复杂志

Objective To observe the effects of low frequency transcranial magnetic stimulation (LF-TMS) on the electroencephalogram (EEG),expression of NPY in hippocampus in pilocarpine (PLO)-induced epileptic rats. Methods Forty male Sprague-Dawley rats (240-260 g) were used to establish a model of epilepsy by in- tradominal injection of pilocarpine,and then randomized into 2 groups:a control group and an intervention group. The control group was treated by sham LF-TMS,while the intervention group was treated by LF-TMS once daily for 7 days.Ⅰgroup simply celiac inject pilocarpine.Ⅱgroup celiac inject PLO after LF-TMS.The EEG was recorded in both groups and the checked pathology.Pathological item include HE staining,NPY immunohisto chemical staining. Results The latency for seizure attack was significantly lengthened,while the frequency of seizure attack and times of major seizure attack were significantly decreased in the intervention group.The HE staining revealed significant de- generation and necrosis of neurons in the hippocampus,especially in the CA3 region,in rats in the control group. The pathologic changes were significantly less severe in the intervention,Immunohistochemical staining showed a sig- nificantly higher expression of NPY in the hippocampus as compared with the intervention group. Conclusion U- sing the PLO-induced epilepsy model,LF-TMS could not only postpone the generation of kindling but also inhibit the progress of epilepsy.The increased NPY expression in the hippocampusin the intervention group implied a close rela- tionship between NPY and epilepsy attack.