Association between the Lymphocyte-to-C-Reactive Protein Ratio and Survival Outcomes in Cancer Patients with GLIM-Defined Malnutrition: A Multicenter Study.

BACKGROUND AND AIMS: This study assessed the prognostic value of LCR in patients with cancer-associated malnutrition (CAM). Systemic inflammatory markers, particularly the lymphocyte-to-C-reactive protein ratio (LCR), are related to the survival of patients with CAM. The present retrospective analysis based on a prospective multicenter cohort study, which involved 1,437 hospitalized patients with CAM. METHODS: The area under the receiver operating characteristic curve (AUC) of ten inflammatory indicators-LCR, advanced lung cancer inflammation index, neutrophil-to-lymphocyte ratio, prognostic nutritional index, modified Glasgow prognostic score, systemic immune-inflammation index, albumin-to-globulin ratio, LCR score, glucose-to-lymphocyte ratio, and platelet-to-lymphocyte ratio-were constructed. Nutritional status, blood markers, and quality of life (QoL) were evaluated within 48 h of admission. The overall survival (OS) was evaluated from September 1 to December 29, 2021. RESULTS: A total of 1,431 cancer patients diagnosed with malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria. Male patients were 62.8% of all, and the mean age was 60.66 years old. The AUC of LCR was higher than that of other inflammatory markers. The restricted cubic spline (RCS) of the Hazard ratios (HRs) showed an inverse L-shaped relationship with LCR. In addition, patients with low LCR had significantly poorer OS than those with high LCR. The addition of LCR to the model increased the predictive ability of 1-year mortality (AUC increase of 0.036), 3-year mortality (AUC increase of 0.038), and 5-year mortality (AUC increase of 0.031). CONCLUSIONS: Assessing the LCR can help the medical staff identify cancer patients with nutritional deficiency at high risk of oncological outcomes and develop individualized therapeutic strategies.

[Effects of autologous adipose-derived stromal vascular fraction on erectile dysfunction of hypertensive rats].

OBJECTIVE: To study the effect of autologous adipose stromal vascular fraction (SVF) injection into corpora cavernosa on the hypertension-associated erectile dysfunction (ED) in rats and its possible mechanism. METHODS: Healthy male spontaneously hypertensive rats (SHR) at 30-week (n=40) and homologous rats with normal blood pressure (WKY) (n=20) were selected. Noninvasive blood pressure meter was used to measure the systolic blood pressure (SBP) at the tail. Cervical subcutaneous injection of apomorphine was applied to test penile erectile function. The rats with ED were divided into hypertension-associated ED rats treated with autologous SVF injection into corpora cavernosa (ED-SHR-SVF group) (n=8) and hypertension-associated ED rats treated with phosphate buffered saline (PBS) injection into corpora cavernosa (ED-SHR-PBS group) (n=8). The intracavernosal pressure (ICP) was measured in each group. Western blot and RT-PCR were conducted to test protein and mRNA expressions of endothelial nitric oxide synthase (eNOS) in corpora cavernosa. RESULTS: The tail SBP in SHR rats was significantly higher than that in WKY rats ((197.47±6.82) mmHg vs (125.23±4.65) mmHg, P<0.05). The erectile rate in SHR rats was 60% (24/40), and that in WKY rats was 100% (20/20). After 5 V electrical stimulation, the ICP in the ED-SHR-SVF group was significantly higher than in the ED-SHR-PBS group ((83.42±3.21) mmHg vs (52.37±3.11) mmHg, P<0.05). The protein and mRNA expressions of eNOS in the ED-SHR-SVF group were significantly higher than in the ED-SHR-PBS group (0.43±0.03 vs 0.18±0.05, 0.92±0.05 vs 0.41±0.06, both P<0.05). CONCLUSIONS: High blood pressure can cause ED in rats, which could be mitigated by autologous SVF injection. The mechanism may be related to up-regulation of eNOS expression in corpus cavernosa.

Prostate stem cell antigen rs2294008 (C>T) polymorphism and bladder cancer risk: a meta-analysis based on cases and controls.

Several published articles have evaluated the association between the prostate stem cell antigen (PSCA) rs2294008 (C>T) polymorphism and bladder cancer risk, but the results remain inconclusive. In order to derive a more precise estimation of the association, we performed a meta-analysis of four case-control studies that included 9617 cases and 16,323 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. Our meta-analysis showed that, overall, the rs2294008 (C>T) polymorphism was associated with bladder cancer susceptibility (OR = 1.29, 95%CI = 1.20-1.40 for TT vs CC; OR = 1.24, 95%CI = 1.16-1.31 for CT vs CC; OR = 1.25, 95%CI = 1.18-1.33 for TT/CT vs CC; OR = 1.13, 95%CI = 1.06-1.20 for TT vs CT/CC). In the stratified analyses, the risk remained significant for studies of European populations, Asian populations, population-based studies, and hospital-based studies. In conclusion, the results suggest that the PSCA rs2294008 (C>T) polymorphism is a risk factor for bladder cancer development.

The renoprotective effect of bone marrow-derived endothelial progenitor cell transplantation on acute ischemia-reperfusion injury in rats.

OBJECTIVE: To investigate the renoprotective effects of exogenous endothelial progenitor cells (EPCs) on acute renal ischemia-reperfusion (I/R) injury in rats. METHODS: EPCs were collected by in vitro culture of mononuclear cells derived from rat bone marrow. The EPC labeling was performed using chloromethyl-benzamidodialkylcarbocyanine (CM-Dil). Sprague-Dawley rats were equally randomized into an I/R, an EPC, and a control group. We evaluated blood urea nitrogen (BUN) and serum creatinine (Scr), kidney morphology, apoptosis and microvessel density. EPC homing into I/R injured kidneys was observed using a fluorescence microscope. RESULTS: After EPC transplantation, CM-Dil-labeled EPCs were noted at the corticomedullary junction of injured kidneys. The levels of BUN and Scr were markedly lower among the EPC than the I/R group (P < .05). The histopathologic score was higher in the I/R than the EPC group (P < .05). Apoptosis of tubular epithelial cells was substantially reduced among EPC-treated rats (P < .01). In addition, more CD34(+) microvessels were documented among the EPC than the other two groups (P < .01). The expression levels of vascular endothelial growth factor (VEGF) were also increased greatly in the EPC group (P < .05). CONCLUSION: Transplanted exogenous EPCs exert protective effects on renal function by maintaining the integrity of peritubular capillaries after I/R injury.

Effects of ischemic preconditioning in the late phase on homing of endothelial progenitor cells in renal ischemia/reperfusion injury.

OBJECTIVE: The aim of this study was to determine whether the mobilization and recruitment of endothelial progenitor cells (EPCs) contribute to the protection of kidneys from ischemia/reperfusion (I/R) injury after ischemic preconditioning (IPC) during the late phase. METHODS: Seventy-five male Sprague-Dawley rats were divided into the following groups: sham-operated (group A; n = 25), ischemia/reperfusion hosts that underwent 45 minutes of left renal artery ischemia (group B; n = 25), and ischemic preconditioning-treated group (group C; n = 25). Group C underwent 3 cycles of 5 minutes of occlusion and 5 minutes of reperfusion followed by 24 hours of reperfusion before the following 45 minutes of occlusion. Serum samples were collected and renal tissues harvested for histological examination terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemical staining, and Western blot analysis to determine the expression levels of CD34, VEGFR-2 (Vascular Endothelial Growth Factor Receptor 2)/flk-1, vascular endothelial growth factor (VEGF), and stromal cell-derived factor-1α (SDF-1α). RESULTS: Compared with group B, the levels of blood urea nitrogen (BUN), serum creatinine (Scr) and acute tubulointerstitial injury at 24 hours after operation were significantly reduced in group C. At 72 hours, tubular epithelial cell apoptosis was also decreased (17.6 ± 4.45 vs 63.8 ± 6.10; P < .01). CD34+ and flk-1+ cells that mostly accumulated in the medullopapillary parenchyma were significantly increased at 72 hours (P < .05). Expression levels of VEGF and SDF-1α were also significantly higher in group C (P < .05). CONCLUSION: The present work suggested that IPC protected kidneys from IR injury in the later phase through enhanced mobilization and recruitment of EPCs. VEGF and SDF-1α may play important roles in this protective effect.

Adrenergic modulation of a spinal sympathetic reflex in the rat.

Patients with spinal cord injury involving transection of the lower cervical or upper thoracic spinal cord can experience an autonomic hyperreflexia characterized by exaggerated blood pressure increases in response to visceral or somatic stimuli such as skin stimulation and urinary bladder or rectal distention. These cardiovascular responses are mediated by activation of spinal sympathetic reflex (SSR) circuits in the segments below the transection that are no longer controlled by their supraspinal inputs. We have examined the SSR in decerebrate, unanesthetized, paralyzed, artificially ventilated rats after acute spinal transection in the sixth cervical segment and have determined its sensitivity to i.v. administration of clonidine and other agents interacting with alpha-2 adrenergic receptors. The SSR amplitude, determined as the area of the averaged excitatory potential evoked on the splanchnic sympathetic nerve by single stimuli (300 microA) applied to the seventh thoracic dorsal root, was reduced to 14% +/- 6% of control with a cumulative dose of clonidine of 27 micrograms/kg. This inhibition was completely reversed by rauwolscine, idazoxan and RX821002, but not by prazosin. Both guanabenz and UK-14304 also reduced the SSR amplitude (9% +/- 3% of control at 0.4 mg/kg and 11% +/- 6% of control at 0.08 mg/kg, respectively). These results indicate that activation of alpha-2 adrenergic receptors, within either the dorsal or intermediolateral horns of the spinal cord or within sympathetic ganglia, can significantly reduce transmission of information through SSR circuits after spinal cord injury.

Cellular electrophysiological changes induced in vitro by radiofrequency current: comparison with electrical ablation.

The purpose of this study was to examine the cellular electrophysiological effects of radiofrequency energy delivery in an in vitro canine epicardial preparation and compare the effects of those of high energy electrical ablation in a similar preparation. Ten joules of direct current energy or 40 volts of radiofrequency energy were delivered by a 6 French 2-mm tip catheter to the epicardial surface of 2 x 3 cm epicardial strips superfused with Tyrode's solution. Direct current energy delivery produced a crater and central zone of necrosis surrounded by a border zone of viable but damaged tissue that extended up to 10-12 mm from the site of energy delivery. Cellular electrophysiological abnormalities that included a less negative resting membrane potential, decreased peak dV/dT, decreased action potential amplitude, and decreased action potential duration (APD) were approximately linearly related to the distance from the crater edge. In addition, viable and inexcitable cells were frequently interspersed. Between 2 and 5 mm from the crater edge, 36.4% of the cells were inexcitable whereas others displayed normal action potential characteristics. In contrast, radiofrequency current produced a central zone of necrosis surrounded by a smaller border zone. Cellular damage that was qualitatively similar to that produced by direct current energy extended only up to 6-8 mm from the edge of the crater. In addition, severe abnormalities were noted in intracellular potentials recorded within 2 mm of the ablation site, and only minor abnormalities further away. Lesions were relatively homogeneous. Between 2 and 5 mm from the ablation site only 2.6% of the cells were inexcitable (P < 0.05 vs direct current). In conclusion, radiofrequency current produces lesions that are smaller and more homogeneous than those produced by direct current ablation. Although the border zone is small, a region of partially depolarized but viable myocardium is present after radiofrequency current energy delivery. These findings provide a cellular basis for several clinical observations that have been made following radiofrequency current energy delivery.

Spatial and temporal linking of epicardial activation directions during ventricular fibrillation in dogs. Evidence for underlying organization.

BACKGROUND: It remains controversial as to whether electrical activation during ventricular fibrillation (VF) is organized. To detect the presence of organization in VF, the direction of epicardial activation (EA) at multiple sites was examined by using vector mapping. If VF is not a random process, EA direction at a given site should be related to adjacent sites and prior beats. METHODS AND RESULTS: Thirteen dogs with healing myocardial infarction (MI) and four dogs without MI had VF induced by programmed stimulation. Using a plaque electrode array with a 2.5-mm interelectrode distance, 91 vector loops were created for each "beat" of VF. Direction of maximum EA was determined at each site for the first 10 consecutive beats of VF and for 10 consecutive beats recorded 5 seconds after VF was established. Spatial and temporal linking of EA directions was evaluated by the ability of activation direction at a given site to be predicted by activation directions at eight adjacent sites for the index beat and at eight adjacent sites and the site of interest for the preceding beat using stepwise linear regression. The strength of the model as reflected by the correlation coefficient (r) indicated the degree of linking. We determined 1) changes in the degree of linking over time during a given episode of VF (using a paired-difference t test), 2) differences in the degree of linking between the anterior and posterolateral walls in animals with (n = 4) and without (n = 4) MI (using two-way ANOVA), and 3) the effect of repeated inductions (n = 10) on the degree of linking (using one-way ANOVA with repeated measures). During 57 episodes of VF, r for each model ranged from 0.64 to 0.88 during the transition to VF to 0.39-0.78 during established VF (p < 0.0001 for the difference). The presence of MI, the site of recording, and repeated inductions did not affect the degree of linking. For each episode, spatial linking was more prominent than temporal linking. CONCLUSIONS: Electrical activation during VF is organized. The degree of linking of EA directions during VF is not affected by the presence of MI, the site of recording, or repeated inductions of VF. During the first 5 seconds of VF, the degree of linking decreases.

Monophasic action potential duration during programmed electrical stimulation.

UNLABELLED: To examine changes in monophasic action potential duration (APD) with a pacing protocol similar to that used during electrophysiological testing, action potentials were recorded in vivo from the left ventricular apical endocardium of 12 normal mongrel dogs. The atrioventricular node was ablated and the dogs paced from the anterior right ventricle at a baseline cycle length of 1000 ms between interventions. Mean steady-state APD (APDss) was 266 +/- 7 ms at a pacing cycle length (PCL) of 1000 ms. Two pacing protocols were used. The first consisted of a sudden acceleration in pacing from a cycle length of 1000 ms to one between 300 and 600 ms. The second consisted of an 8-beat train at a cycle length of 400 ms followed by a premature beat at a coupling interval of 280 ms followed by a pause. The inter-train pause varied between 1 second and 32 seconds. With a sudden acceleration in pacing rate, steady-state values for APD at the faster PCLs were significantly smaller than APDss at 1000 ms with a change to cycle lengths of 600 ms (247 +/- 29 ms), 500 ms (229 +/- 21 ms), 400 ms (220 +/- 17 ms), and 300 ms (203 +/- 31 ms; P less than 0.01 for all comparisons). The time constant of the change in APD was shorter at a PCL of 300 ms (14.9 +/- 0.8 s) than 600 ms (20.3 +/- 4.7 s; P less than 0.05). With drive train pacing and incorporating an inter-train pause, the percent drop in steady-state APD compared to APD for the first train ranged from 10.1% with a 1-second inter-train pause to 2.1% with a 32-second pause. The difference in APD between the first drive train and drive trains after at least 3 minutes of pacing when APD had stabilized was not significant for an inter-train pause exceeding 8 seconds. IN CONCLUSION: (1) with a sudden acceleration in pacing rate, endocardial APD in vivo decreases exponentially. The faster the new rate, the shorter the new steady-state APD and the shorter the time constant. (2) When pacing using an 8-beat drive train and an inter-train pause, there is a decremental shortening in APD for pause lengths shorter than 16 seconds. Thus, while performing programmed stimulation using a pause, a conditioning period of at least 2 minutes should be used prior to diastole scanning to allow APD to achieve a steady state.