Influence of lymph node dissection in patients undergoing radical nephrectomy for non-metastatic renal cell carcinoma: a systematic review and meta-analysis.

OBJECTIVE: Whether lymph node dissection (LND) should be performed concomitantly with radical nephrectomy (RN) for non-metastatic renal carcinoma has still been controversial recently. We conducted a meta-analysis assessing oncologic outcomes of radical nephrectomy with lymph node dissection (LND) and without lymph node dissection (non-LND) in non-metastatic renal cell carcinoma (NMRCC). PATIENTS AND METHODS: A systematic review was performed until April 2018 using a comprehensive search in PubMed, EMBASE, and Cochrane Library databases to identify eligible comparative studies. A formal meta-analysis was performed for studies comparing radical nephrectomy with LND and radical nephrectomy with non-LND for cT1-T4NxM0 tumors. Furthermore, a subgroup analysis for locally advanced renal cell carcinoma (cT3-T4NxM0) was conducted. RESULTS: Thirteen studies on patients with LND and non- LND were identified and included in the analysis. LND group did not have a significantly better survival than non-LND group for cT1-T4NxM0 tumors (HR 0.93, 95% CI 0.78-1.11, p=0.45), However, in the subgroup of locally advanced renal cell carcinoma (cT3-T4NxM0), it showed a significantly better OS rate in patients who had undergone LND compared to those without LND (HR 0.73, 95% CI 0.60-0.90; p=0.003). CONCLUSIONS: LND offers better cancer control and better long-term survival in locally advanced renal cell carcinomas (cT3-T4NxM0). This conclusion should be confirmed by a prospective randomized clinical trial.

Knockdown of HJURP inhibits non-small cell lung cancer cell proliferation, migration, and invasion by repressing Wnt/ß-catenin signaling.

OBJECTIVE: Holliday junction-recognizing protein (HJURP) was found to be upregulated in several tumors, including non-small cell lung cancer (NSCLC), and the effect of HJURP on NSCLC remains unknown. The objective of the present study was to explore the clinical significance of HJURP and its function in regulating the progression of NSCLC. PATIENTS AND METHODS: Reverse Transcriptions-Polymerase Chain Reaction (RT-PC) and Western blot were performed to detect the expression levels of HJURP in NSCLC tissues and cell lines. The association of HJURP expression level with various important clinicopathological parameters was evaluated. Then, the effects of HJURP expression on tumor cell behavior in vitro were analyzed by the Cell Counting Kit-8 (CCK-8), EdU assays, colony formation, flow cytometry, and transwell assays. The protein levels of related proteins of the Wnt/ß-catenin pathway were determined using the Western blot assay. RESULTS: Our study showed that HJURP was significantly upregulated in both NSCLC tissues and cell lines. The higher expression of HJURP was associated with advanced TNM stage, distant metastasis, and poor prognosis. Our data from in vitro assays confirmed that the knockdown of HJURP suppressed NSCLC cells proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) progress, and induced cells apoptosis. Notably, through Western blot analysis, we found that HJURP suppression remarkably decreased ß-catenin, cyclin D1 and c-myc expression level in NSCLC cell lines. CONCLUSIONS: Our findings provide clues regarding the role of HJURP as a tumor promoter in NSCLC via the activation of the Wnt/ß-catenin pathway, indicating HJURP may be a promising therapeutic target for NSCLC.

A pilot study using the Chinese herbal paste Liu-He-Dan to manage radiodermatitis associated with breast cancer radiotherapy.

BACKGROUND: During radiotherapy for breast cancer, patients are greatly affected by pain, infection, and delayed healing of wounds caused by radiodermatitis. In the present study, we aimed to determine the efficacy of Liu-He-Dan in treating radiodermatitis. METHODS: In 26 breast cancer patients who experienced moist decrustation while receiving radiotherapy, 5 g Liu-He-Dan was applied externally once daily after the wound surface had been cleaned and dried. The healing time was recorded, and a Kaplan-Meier survival curve was applied to analyze the treatment course. Meanwhile, a pain assessment using the Numeric Rating Scale (nrs) recorded the pain level experienced by patients after application of the Liu-He-Dan. RESULTS: After application of Liu-He-Dan, the average healing time for the surface of the moist decrustation wounds was 14.17 ± 2.03 days (range: 5-22 days). Inflammatory seepage decreased significantly and exudation almost disappeared in 3 days. The pain trend line indicated that the average nrs score declined with treatment in all patients. The average nrs scores at days 1, 4, and 7 were 6.13, 3.62, and 2.58 respectively. After 3 days of treatment, pain was remarkably alleviated in 80.76% of patients. After treatment for 1 week, the pain remission rate was 96.15%, without any obvious adverse reactions. CONCLUSIONS: Liu-He-Dan was efficacious in treating radiation skin injury with little toxicity and few side effects; the economic efficiency of the treatment was also favourable. The Liu-He-Dan was generally well tolerated by patients. In future, randomized control trials will be established for further observation of the value of Liu-He-Dan in treating radiodermatitis in breast cancer.

The effect of variable practice on wheelchair propulsive efficiency and propulsive timing.

AIM: The net mechanical efficiency of wheelchair propulsion is very low, approximately 13%. It is necessary to look for effective practice methods to obtain greater output with less energy expenditure during wheelchair propulsions. Literature indicates that variable practice (VP) is more effective than constant practice (CP) in motor-skill learning. However, it is unknown if VP is more effective than CP in improving wheelchair propulsive efficiency. The purpose of the study was to determine how propulsive efficiency and propulsive timing were affected by variable practice and constant practice. DESIGN: This was an observational and experimental study. SETTING: The experiment was conducted in a well-controlled university research laboratory. POPULATION: A total of 33 able-bodied subjects participated in this study. METHODS: Participants were randomly placed into one of the three training groups, two constant practice groups and one variable practice group. One constant group practiced wheelchair propulsion on a roller system with a single speed, 30% of the maximum speed, while the other constant group practiced using 55% of the maximum speed. The variable group practiced with both speeds. Three dependent variables, propulsive efficiency, timing, and intercycle variability of the timing, were measured. RESULTS: All groups improved the three dependent variables significantly after the training, and in general the VP group had greater improvement than the others in improving the propulsive efficiency. CONCLUSION: This study is the first to demonstrate the advantage of the VP over the CP in improving the propulsive efficiency. CLINICAL REHABILITATION IMPACT: This finding has great implication for paraplegics because they require greater workloads for upper-extremity activities.

Exercise preconditioning upregulates cerebral integrins and enhances cerebrovascular integrity in ischemic rats.

We hypothesized that exercise preconditioning strengthens brain microvascular integrity against ischemia/reperfusion injury through the tumor necrosis factor (TNF)-integrin signaling pathway. Adult male Sprague Dawley rats (n = 24) were studied in: (1) exercise (the animals run on a treadmill 30 min each day) for 3 weeks, (2) non-exercise. Six animals from each group (n = 12) were subjected to stroke, the remaining animals served as controls (n = 6 x 2). Brain infarction and edema were determined by Nissl staining. Cerebral integrin expression was detected by immunochemistry and stereological methods. In addition, we used flow cytometry to address the causal role of TNF-alpha in inducing the expression of integrins in the human umbilical vein endothelial cells under TNF-alpha or vascular endothelial growth factor (VEGF) pretreatment. Exercise reduces brain infarction and brain edema in stroke. Expressions of integrin subunit alpha(1), alpha(6), beta(1), and beta(4) were increased after exercise. Exercise preconditioning reversed stroke-reduced integrin expression. An in vitro study revealed a causal link between the gradual upregulation of TNF-alpha (rather than VEGF) and cellular expression of integrins. These results demonstrated an increase in cerebral expression of integrins and a decrease in brain injury from stroke after exercise preconditioning. The study suggests that upregulation of integrins during exercise enhances neurovascular integrity after stroke. The changes in integrins might be altered by TNF-alpha.

Effect of sea anemone toxin anthopleurin-Q on sodium current in guinea pig ventricular myocytes.

AIM: To investigate the effects of a sea anemone toxin anthopleurin-Q (AP-Q) isolated from Anthopleura xanthogrammica on sodium current (INa) in isolated guinea pig ventricular myocytes. METHODS: Single myocytes were dissociated by enzymatic dissociation method. INa was recorded using whole-cell patch-clamp technique. RESULTS: AP-Q (3 - 300 nmol/L) increased INa in a concentration-dependent manner. The EC50 value for increasing INa was 104 nmol/L (95 % confidence range: 78 - 130 nmol/L). AP-Q 300 nmol/L shifted the I-V curve to the leftward, changed the membrane potential of half maximal activation to more negative potential from (-36.3 +/- 2.3) mV to (-43 +/- 3) mV (n = 6, P < 0.01) and changed the membrane potential of half maximal inactivation to more positive potential from (-75 +/- 6) mV to (-59 +/- 5) mV (n = 6, P < 0.01). AP-Q 300 nmol/L shortened the half-recovery time of INa from (114 +/- 36) ms to (17 +/- 2) ms (n = 6, P < 0.01). The fast inactivation time constant (tauf) of INa was markedly increased by AP-Q 300 nmol/L. CONCLUSION: AP-Q has a stimulating effect on I(Na) with slowing the inactivation course of INa.

[Effects of 4-aminopyridine on calcium currents and sodium currents in guinea pig ventricular myocytes].

AIM: To investigate the effect of 4-aminopyridine (4-AP) on ion channels of myocytes. METHODS: L-type calcium channel and sodium channel currents were recorded in guinea pig single ventricular myocyte using whole-cell patch-clamp techniques. RESULTS: 4-AP, 0.1, 0.5 and 1.0 mmol.L-1 were shown to inhibit L-type calcium channel currents (ICa, L) and sodium channel currents (INa) concentration-dependently. The percentage of inhibition were (11.6 +/- 1.7)%, (37.5 +/- 8.3)% and (54.5 +/- 6.9)% (P < 0.01) respectively for ICa, L, and (22.1 +/- 14.3)% (P < 0.05), (39.4 +/- 8.8)% and (62.3 +/- 6.8)% (P < 0.01) respectively for INa. 4-AP 0.5 mmol.L-1 shifted the I-V curves of ICa, L and INa upwardly. CONCLUSION: 4-AP blocked L-type calcium channel and sodium channels in guinea-pig ventricular myocytes concentration-dependently.

[Effects of amiloride on calcium current in thyroxine-induced hypertrophied rat heart].

AIM: The L-Type calcium currents were investigated in normal, hypertrophied and amiloride-treated rat ventricular myocytes so as to clarify the possible cause of the action potential lengthening that has been reported in thyroxine-induced hypertrophy. The interactions between agents such as thyroxine, Ang II and phenylephrine which induced hypertrophy with amiloride on the calcium current were analyzed. METHODS: Myocardial hypertrophy was induced by i.p. L-thyroxine in rats. The cell length, cell width and cell area were measured by image analysis technique. For recording ICaL, the whole cell patch clamp technique was used. Potassium currents were suppressed by replacing K+ ions with Cs+ ions in intracellular media, and sodium current was blocked by 50 mumol.L-1 tetrodotoxin. RESULTS: The Ca2+ current was found to be larger in hypertrophied cells (783pA) than in normal cells (433pA) and in amiloride-treated cells (429pA). However, no significant difference was observed in current density (6.54, 8.33, 5.74 pA/pF) in normal, hypertrophied and amiloride-treated cells. ICa displayed the same voltage dependence in three cell types. The potential giving 50% of activation (V1/2) moved towards more negative and the slope of activation curve was smaller in hypertrophied cells than in normal cells and amiloride cells. When expressed as percentages, the maximal increases in ICa were obtained with 1 mumol.L-1 Ang II and 100 mumol.L-1 phenylephrine in normal cells (+45.5% and +81.8%). Thyroxine 100 mumol.L-1 showed no effect on ICa. After giving amiloride, Ang II and phenylephrine did not increase the amplitude of ICa. CONCLUSION: At the dose of 0.5 mg.kg-1.d-1, amiloride (p.o.) was shown to prevent the amplitude of ICa from increasing and to be effective against increases of amplitude of ICa by Ang II and phenylephrine.

Kinematic characteristics of aiming movements as a function of temporal and spatial constraints.

This study investigated, in aiming movements, the conditions needed to produce a single movement and those needed to produce secondary submovements. Using a 2x2 (Temporal Constraint x Spatial Constraint) factorial design with repeated measures on both factors, subjects moved a stylus from a starting position to a target position 12 cm away. They participated in two testing sessions on consecutive days. The first session involved two nonrestrictive target (a set of crosshairs) conditions, moving to the target either within a goal of 400 ms (temporal-accuracy procedure) or within a minimum time (time-minimization procedure). In the second session the subjects performed two strict-target (circle) conditions, moving to the target either within a goal of 400 ms or within a minimum time. The results showed that the two strict-target conditions had a greater percentage of trials containing multiple-submovements than the two nonrestrictive target conditions, regardless of temporal requirements. Therefore, whether an aiming movement contains a single movement or multiple submovements may be a function of spatial constraints regardless of temporal constraints. It appears that with respect to the nature of the speed-accuracy tradeoff, spatial constraints are an important factor.

Blocking L-calcium current by l-tetrahydropalmatine in single ventricular myocyte of guinea pigs.

AIM: To study the effect of l-tetrahydropalmatine (l-THP) on L-type calcium channel. METHODS: Patch clamp technique (whole cell recording) was used to record L-Ca2+ current in single cardiac myocyte. RESULTS: 1) l-THP 1, 10, and 100 micromol.L-1 reduced ICa-max from (999 +/- 93) pA to (700 +/- 111) pA, (582 +/- 66) pA, and (420 +/- 112) pA (n = 6, P < 0.01), respectively. 2) l-THP reduced the voltage at half-maximal inactivation (V1/2) of L-Ca2+ channel to more negative potentials by 9 mV (n = 5, P < 0.05). 3) l-THP caused both tonic and use-dependent reduction of Ca2+ current. Tonic block of l-THP on Ca2+ current was 46% +/- 8% (n = 6, P < 0.01). The degree of use dependent blocking was 13.5% +/- 2.4% (n = 6, P < 0.05) at 1 Hz, the degree increased to 44% +/- 5% (n = 6, P < 0.01) at 3 Hz. 4) l-THP delayed half-recovery time of Ca2+ channel recovery from inactivity from (94 +/- 39) ms to (170 +/- 42) ms(n = 6, P < 0.01). CONCLUSION: l-THP has a moderate inhibitory effect on L-Ca2+ current.

[The synergistic effect of tetrandrine and rotundine on the action potential of rabbit sinus node dominant pacemaker cell and calcium currents of ventricular myocytes from guinea-pig].

Standard microelectrode technique and the whole-cell clamp technique were used to investigate the effects of tetrandrine and rotundine on the action potential of rabbit sinus node dominant pacemaker cell and calcium currents of ventricular myocytes from guinea-pig. The results indicate that: tetrandrine 1-200 mumol.L-1 and rotundine 3-300 mumol.L-1 decreased the action potential amplitude(APA), the maximal upstroke velocity (Vmax), spontaneous depolarizing velocity of phase 4(SP4) and prolonged the sinus circle length(SCL) in a dose-dependent manner. Tetrandrine 0.1 mumol.L-1 in combination with rotundine 0.3 mumol.L-1 was shown to effectively reduce the ICa of ventricular myotytes from guinea-pig, the rate of inhibition is 19.6%. The results suggest that the two drugs have a good synergistic effect on inhibiting calcium current. These results might also put forward a valuable theoretic base for using the two drugs together in treating patients.

Effects of 7-bromoethoxybenzene-tetrahydropalmatine on voltage-dependent currents in guinea pig ventricular myocytes.

AIM: To study the anti-arrhythmic mechanism of 7-bromoethoxybenzene-tetrahydropalmatine (EBP). METHODS: Whole-cell current and voltage clamp on isolated guinea pig ventricular cells. RESULTS: EBP 30 mumol.L-1 prolonged APD90 from 430 +/- 47 ms to 514 +/- 61 ms (n = 5, P < 0.05) without effects on the action potential amplitude and resting potential. Delayed outward K+ current and its tail current were blocked by EBP in a concentration-dependent fashion, while EBP did not change the amplitudes of the sodium current, the L type calcium current, and the inwardly rectifying potassium current. CONCLUSION: The mechanism of anti-arrhythmic action of EBP was to prolong the APD through inhibiting the delayed rectified potassium current.

[Blocking effects of benzyltetrahydropalmatine on delayed rectified K+ currents expressed in Xenopus oocytes and in toad oocytes].

The effects of benzyltetrahydropalmatine (BTHP) on delayed rectified K+ currents (Ik) expressed in Xenopus oocytes and Ik of toad (Bufo bufo gargarizans) oocytes were studied. The Ik expressed in Xenopus oocytes was measured after microinjection of mRNA isolated from carp fish (C anratus L.) brains with double -microelectrode voltage clamp technique. The maximum and mean value of Ik expressed in Xenopus oocytes were 600 nA and 360 +/- 104 nA, respectively. BTHP reduced the current amplitude of Ik expressed in Xenopus oocytes in 10-1000 mumol.L-1 dose-dependently, EC50 was 29 mumol.L-1. Also, the reduction of Ik of toad oocytes was 9.1%, 29.1%, 54.7% and 68.6% by BTHP 10, 30, 100 and 1000 mumol.L-1, respectively, EC50 was 33 mumol.L-1. The results showed that BTHP possesses an inhibitory effect on Ik, the main ion mechanism of antiarrhythmic action of BTHP.

[Protective effects of tetrandrine on ischemic myocardia in anesthetized dogs].

The present study indicates that iv tetrandrine may transiently decrease blood pressure, while other hemodynamic parameters such as LVP, +/- dp/dtmax, LVEDP, HR and CO may not be significantly altered. During coronary occlusion three of five dogs developed ventricular fibrillation (VF) and died in the control group, i.e. incidences of VF and mortality were 60%. While tetrandrine (Tet) appeared to reduce the severity of ischemic injury. It may alleviate arrhythmia and prevent VF and death in four of the five dogs. Tet also attenuated Ca2+ accumulation in myocardial cell, reduced melondialdehyde (MDA) production in ischemic myocardial and decreased CPK release in comparison with the control. It appears that Tet may have significant protective effects against ischemia induced cardiac damage in anesthetized dogs.

Motor skill acquisition and retention as a function of average feedback, summary feedback, and performance variability.

Summary feedback involves withholding feedback from subjects until the last trial in a block is completed, and then presenting feedback about each trial. A variation of this method, called average feedback (Young & Schmidt, 1992), presents subjects with only the mean of the trial block. We investigated whether these methods have similar effects on acquisition and retention of a simple motor skill. Five groups of subjects (n = 16 per group) performed 60 acquisition trials of an aiming task involving both spatial and temporal accuracy. We presented average and summary feedback based on either 5-trial blocks or 15-trial blocks and compared these schedules with every-trial feedback. During acquisition, all groups improved with practice, with a slight tendency for the every-trial condition to have less absolute error than the longer summary and average conditions. Analysis of delayed no-feedback retention tests, however, revealed a strong advantage for the 5-trial summary and average conditions compared with the every-trial condition. In addition, we found that for long blocks of acquisition trials without augmented feedback, the performance variability of those trials was associated with retention performance. Results are discussed in terms of how these different manipulations may make feedback less useful during acquisition, but foster the use of certain information processing activities that enhance overall learning.

Evidence limiting the subtended-angle hypothesis of response-programming delays.

In 1991 Sidaway proposed an alternative explanation to account for the traditional effect of response complexity on programming time. He suggested that rather than number of movement parts per se, it is the directional accuracy demand of a response, as quantified by the "subtended angle," that constrains the movement initiation and produces programming delays. In Sidaway's experiments targets were positioned so that the first target was always closest to the starting position, with subsequent targets positioned further away from the start. This study tested the subtended-angle hypothesis by placing the first target furthest from the starting position, with subsequent targets struck by reversing direction and coming back toward the start. 30 subjects performed two aiming responses, a discrete 1-TAP condition and a serial 3-REVERSE condition. Because the subtended angle was identical in both conditions, there should be no difference in programming time. Our analyses, however, showed a significant effect for number of targets. Mean reaction time was longer for 3-REVERSE than for 1-TAP. These results argue against a strict constraint interpretation based on subtended angle and suggest that, under certain conditions, number of movement parts can still affect delays in response programming.

[Effects of linesinine on slow action potentials in myocardium and slow inward current in canine cardiac Purkinje fibers].

Standard microelectrode and two-microelectrodes voltage clamp techniques were used to study the effects of linesinine (Lien), an alkaloid extracted from the green seed embryo of Nelumbo nucifera Gaertn, on slow action potentials (AP) and slow inward current (Isi). Lien 10-100 mumol/L was shown to concentration-dependently decrease the action potential amplitude (APA), the maximal velocity of phase 0 depolarization (Vmax) and prolong the sinus cycle length (SCL) of slow AP in isolated sinoatrial node (SAN) pacemaker cells of rabbits. On both slow APs of rabbit SAN cells and guinea pig papillary muscles partly depolarized by high K+, Bay K 8644 0.03 mumol/L markedly increased the APA and Vmax, which were obviously antagonized by Lien 10 mumol/L. Moreover, Lien 1-100 mumol/L was found to inhibit the Isi of canine cardiac Purkinje fiber in concentration-dependent manner. Lien 3 and 100 mumol/L reduced the peak value of Isi by 14% and 88% respectively. The results suggest that Lien possesses calcium antagonistic effects.

[Effects of benzyltetrahydropalmatine on rat portal vein and guinea pig myocardium].

In isolated rat portal vein, benzyltetrahydrophalmatine (BTHP) 0.3-100 mumol.L-1 dose-dependently increased the spontaneous mechanical activity. However, BTHP 300 mumol.L-1 showed an inhibitory effect on the spontaneous contraction. BTHP 200 mumol.L-1 reversed positive staircase phenomenon to negative ones in left atrium of guinea pig and inhibited the amplitude and Vmax and shortened the action potential duration (APD50) of the slow action potentials induced by high K+ (24 mmol.L-1) in guinea pig papillary muscles. BTHP reduced also the contractile force in papillary muscles of guinea pig. These results suggest that BTHP possesses calcium antagonistic effect in high concentration.

Effects of benzyltetrahydropalmatine on delayed after depolarization and triggered activity and on His-bundle electrogram and ECG in animal experiment.

Standard microelectrode techniques were used to study the effects of benzyltetrahydropalmatine (BTHP) on ouabain-induced delayed after depolarization (DAD) and triggered activity in isolated guinea papillary muscles. The results indicate that ouabain-induced DAD and triggered activity were abolished by BTHP 100 mumol/L. In anesthetized rabbit ECG heart rate was reduced in a dose-dependent manner from control value of 288 +/- 14 to 261 +/- 14 (BTHP 5 mg/kg) and 226 +/- 36 bpm (BTHP 10 mg/kg). P-R interval was prolonged. In His-bundle electrogram, H-V interval and V duration were not affected, but A-H interval was prolonged from 41 +/- 3 to 45 +/- 5 ms.