Association between the C-reactive protein/albumin ratio and mortality in older Japanese patients with dysphagia.

Background: C-reactive protein-to-albumin ratio (CRP/ALB) has been proven to represent a biomarker for predicting prognosis in many groups of patients with severe diseases. However, few studies have investigated the association between CRP/ALB and mortality in Japan older people with dysphagia patients. Objective: This retrospective cohort study aimed to assess the prognostic value of C-reactive protein/albumin ratio (CAR) in older Japanese patients with dysphagia. Methods: We analyzed data from 253 patients diagnosed with dysphagia at a single center between January 2014 and January 2017. Cox regression analysis was used to compare the mortality rates across the CAR tertiles. Subgroup analyses were conducted, and Kaplan-Meier curves were used to determine the median survival times. Results: The study included 154 female and 99 male patients, with a median age of 83 years. After adjusting for all covariates, the multivariable Cox regression analysis revealed a significant association between increasing CAR (HR = 1.19, 95% CI: 1.03-1.37, P = 0.022) and the risk of mortality. Compared to the reference group T1 (< 0.149), the adjusted hazard ratios for T2 (0.149-0.815) and T3 (> 0.815) were 1.75 (95% CI: 1.07-2.87, P = 0.027) and 2.15 (95% CI: 1.34-3.46, P = 0.002), respectively. Kaplan-Meier curves indicated median survival times of 864, 371, and 223 days for T1, T2, and T3, respectively. Conclusion: The C-reactive protein/albumin ratio was positively related to mortality in Japan older people with dysphagia patients. There was no interaction for the subgroup analysis. The result was stable.

Luteoloside pretreatment attenuates anoxia-induced damage in cardiomyocytes by regulating autophagy mediated by 14-3-3η and the AMPKα-mTOR/ULK1 pathway.

The relation between ischemia and heart failure is well demonstrated, and several studies suggested that realizing the physiological role of autophagy will be of great importance. Luteoloside (Lut) is one of the main components of Lonicera japonica flos and exhibits antioxidant, anti-inflammatory, and cardioprotective properties. To determine if Lut pretreatment enhanced autophagy by 14-3-3η expression and the AMPKα-mTOR/ULK1 pathway and protected the neonatal rat cardiomyocytes (NRCMs) against anoxia damage, NRCMs were treated using 20 µM Lut for 36 h, and the anoxia damage model was established using NRCMs. The indexes reflecting the condition of NRCMs, oxidative stress level, and mitochondrial function were evaluated. In addition, the expression and phosphorylation of 14-3-3η and AMPKα/mTOR/ULK1, and autophagy markers (LC3II, P62) and the abundance of autophagy lysosomes were detected. Results revealed that Lut pretreatment alleviated anoxia- induced damage in NRCMs, that is, Lut pretreatment could increase cell viability, decrease LDH activity and apoptosis, suppressed ROS generation and oxidative stress, restored intracellular ATP levels, stabilized MMP levels, and inhibited mPTP opening. Furthermore, Lut pretreatment could enhance autophagy via upregulating 14-3-3η, LC3II expression and increasing p-AMPKα/AMPKα and p-ULK1/ULK1 level, whereas P62 expression and p-mTOR/mTOR level decreased; the fluorescence intensity of autolysosomes also increased. However, in the NRCMs treated with pAD/14-3-3η RNAi or incubated with 3-MA (an autophagy inhibitor), the abovementioned effects of Lut pretreatment were reduced. Taken together, Lut pretreatment could enhance autophagy by upregulating 14-3-3η expression to influence the AMPKα-mTOR/ ULK1 pathway against anoxia-induced damage in NRCMs.

Luteoloside protects the vascular endothelium against iron overload injury via the ROS/ADMA/DDAH II/eNOS/NO pathway.

Iron overload injury is considered to be a part of blood stasis syndrome of arthralgia in traditional Chinese medicine. Its primary therapies include clearing heat and detoxification, activating blood circulation, and removing blood stasis. Lonicera japonica flos (LJF) has long been known as an excellent antipyretic and antidote. Luteoloside (Lut) is one of the main components of LJF and exhibits antioxidant, anti-inflammatory, and cytoprotective properties. However, the protection of Lut against iron overload injury and its underlying mechanisms remain unclear. Therefore, HUVECs were exposed to 50 µmol·L-1 iron dextran for 48 h to establish an iron overload damage model and the effects of Lut were assessed. Our results showed that 20 µmol·L-1 Lut not only increased cell viability and weakened LDH activity, but also significantly up-regulated DDAHⅡ expression and activity, increased p-eNOS/eNOS ratio and NO content, and reduced ADMA content in HUVECs exposed to iron overload. Furthermore, Lut significantly attenuated intracellular/mitochondrial ROS generation, improved SOD, CAT, and GSH-Px activities, reduced MDA content, maintained MMP, inhibited mPTP opening, prevented cyt c from mitochondria released into cytoplasm, reduced cleaved-caspase3 expression, and ultimately decreased cell apoptosis induced by iron overload. The effects of Lut were similar to those of L-arginine (an ADMA competitive substrate), cyclosporin A (a mPTP blocker agent), and edaravone (a free radical scavenger) as positive controls. However, addition of pAD/DDAH II-shRNA adenovirus reversed the above beneficial effects of Lut. In conclusion, Lut can protect HUVECs against iron overload injury via the ROS/ADMA/DDAH II/eNOS/NO pathway. The mitochondria are the target organelles of Lut's protective effects.

Feasibility of anterior pedicle screw fixation in lumbosacral spine: a radiographic and cadaveric study.

BACKGROUND: The anterior pedicle screw (APS) technique for L5 and S1 is crucial for proper anterior lumbar interbody fusion (ALIF). This study aimed to determine the projection, screw trajectory angle, and bone screw passageway length (BSPL), as well as the screw insertion regularity and the operating area within which it is safe to perform insertion. METHODS: Forty patients with low back pain, all of whom had lumbar computed tomography scans available, was included in this retrospective analysis. Radiographic parameters were measured, including: the distances from the projection to the upper endplate, lower endplate, and midline; the transverse and sagittal screw angles; and the BSPL. In addition, 10 fresh adult cadaveric lumbosacral spine segments were selected to determine the safe anatomic area in which to operate. Finally, APSs were inserted in L5 and S1 to determine the regularity of APS insertion. RESULTS: We measured the anterior projection parameters, including: the distances to the upper endplate (L5: 12.5±1.3 mm; S1: 4.54±0.87 mm), lower endplate (L5: 17.3±1.6 mm), and midline (L5: 6.6±0.7 mm; S1: 6.6±0.6 mm); the screw trajectory angle, including the transverse screw angle (L5: 25.3±2.8°; S1: 25.7±2.6°), sagittal screw angle (L5: 17.1±1.7°; S1: 22.4±1.1°); and the BSPL (L5: 48.6±3.5 mm; S1: 48.0±3.5 mm). The regularity of APS insertion in L5 and S1 was determined. Upon the needle reaching a point in the lateral view, it reached the corresponding point in the anteroposterior (AP) view. The anatomic parameters of the safe operating area were as follows: the distance from the abdominal aortic bifurcation to the L5 lower edge (40.50±9.40 mm); the distance from the common iliac vein confluence to the L5 lower edge (27.80±8.60 mm); and the horizontal distance from the inner edge of the common iliac vein to the L5 lower edge (37.50±1.30 mm). We also determined the distance between S1 holes (29.30±1.30 mm), the L5/S1 intervertebral height (17.20±1.50 mm), and the safe operating area (2,058.20±84.30 mm2). CONCLUSIONS: This study has determined the projection, screw trajectory angle, and BSPL of APSs in L5 and S1, their insertion regularity, and the area in which the operation can be safely performed.

Capsaicin protects cardiomyocytes against lipopolysaccharide-induced damage via 14-3-3γ-mediated autophagy augmentation.

Background: The myocardium is susceptible to lipopolysaccharide (LPS)-induced damage in sepsis, and cardiac dysfunction is a leading cause of mortality in patients with sepsis. The changes in cardiomyocyte autophagy in sepsis and the effects and mechanism of action of capsaicin (Cap) remain unclear. Methods and Results: The potential pathway of 14-3-3γ-dependent autophagy and the effects and mechanisms of Cap were studied in LPS-induced injury to primary cultured neonatal rat cardiomyocytes. The results showed that cardiomyocyte viability decreased, lactate dehydrogenase and creatine kinase activities increased, 14-3-3γ expression was downregulated, and autophagy was inhibited after LPS challenge. Cap pretreatment augmented autophagy by upregulating 14-3-3γ expression and activating AMP-activated protein kinase (AMPK) and unc-51 like autophagy-activating kinase 1 (ULK1), suppressing mammalian target of rapamycin (mTOR), alleviating cardiac dysfunction and improving the inflammation response, whereas pAD/14-3-3γ-shRNA nullified the above effects. Cap pretreatment also decreased the levels of IL-1ß, TNF-α, IL-6, and IL-10; suppressed intracellular oxidative stress; reduced the intracellular/mitochondrial reactive oxygen species (ROS); balanced GSH/GSSG; increased GSH-Px, catalase, and SOD activities; and decreased MDA contents. It also increased ATP content, activated complex Ⅰ and complex Ⅲ, stabilized the mitochondrial membrane potential, and decreased the mitochondrial permeability transition pore opening, thereby improving mitochondrial function. Conclusion: Pretreatment with Cap can regulate autophagy by upregulating 14-3-3γ expression, inhibiting oxidative stress and inflammation, maintaining mitochondrial function, and protecting cardiomyocytes against LPS-induced injury.

Appropriate insertion point for percutaneous pedicle screw placement in the lumbar spine using c-arm fluoroscopy: a cadaveric study.

BACKGROUND: We studied the characteristics and regularity of appropriate insertion points for percutaneous pedicle screw placement in the lumbar spine using C-arm X-ray fluoroscopy. The purpose of this study was to improve the accuracy of percutaneous pedicle screw placement and reduce the incidence of superior-level facet joint violation. METHODS: Six normal spinal specimens were included. Three different methods for placing percutaneous pedicle screws in the lumbar spine were applied, including the Roy-Camille method, Magerl method and Weinstein method. The relationships among the insertion point, pedicle projection and proximal facet joint on C-arm X-ray films were studied. The projection morphology of the vertebral pedicle in different segments of the lumbar spine was observed. The relationship between the outer edge of the pedicle projection and the outer edge of the cranial articular process was also studied. The distance between the insertion point and the facet joint (M1), the distance between the insertion point and outer edge of the cranial articular process (M2), and the distance between the insertion point and the projection center of the pedicle (M) were measured. RESULTS: In this study, we found that the projection shape of the vertebral pedicle differed across segments of the lumbar spine: the shape for L1-L3 was oval, and that for L4-L5 was round. The radiographic study showed that the outer edge of the cranial articular process was located on the lateral side of the outer edge of the pedicle projection and did not overlap with the pedicle projection. M for the Weinstein group was larger than that for the Roy-Camille group (P <  0.05). M1 for the Weinstein group was larger than that for the Roy-Camille and Magerl groups (P <  0.05). M2 for the Roy-Camille group was negative, M2 for the Magerl group was 0, and M2 for the Weinstein group was positive. CONCLUSION: Under C-arm X-ray fluoroscopy, we were able to accurately identify the characteristics and regularity of the appropriate insertion point for percutaneous pedicle screw placement in the lumbar spine, which was important for improving the accuracy of percutaneous pedicle screw placement and reducing the incidence of superior-level facet joint violation.

Capsaicin Alleviates the Deteriorative Mitochondrial Function by Upregulating 14-3-3η in Anoxic or Anoxic/Reoxygenated Cardiomyocytes.

Reactive oxygen species (ROS) are byproducts of a defective electron transport chain (ETC). The redox couples, GSH/GSSG and NAD+/NADH, play an essential role in physiology as internal defenses against excessive ROS generation by facilitating intracellular/mitochondrial (mt) redox homeostasis. Anoxia alone and anoxia/reoxygenation (A/R) are dissimilar pathological processes. In this study, we measured the impact of capsaicin (Cap) on these pathological processes using a primary cultured neonatal rat cardiomyocyte in vitro model. The results showed that overproduction of ROS was tightly associated with disturbed GSH/GSSG and NAD+/NADH suppressed mt complex I and III activities, decreased oxygen consumption rates, and elevated extracellular acidification rates. During anoxia or A/R period, these indices interact with each other causing the mitochondrial function to worsen. Cap protected cardiomyocytes against the different stages of A/R injury by rescuing NAD+/NADH, GSH/GSSG, and mt complex I/III activities and cellular energy metabolism. Importantly, Cap-mediated upregulation of 14-3-3η, a protective phosphoserine-binding protein in cardiomyocytes, ameliorated mt function caused by a disruptive redox status and an impaired ETC. In conclusion, redox pair, mt complex I/III, and metabolic equilibrium were significantly different in anoxia alone and A/R injury; Cap through upregulating 14-3-3η plays a protection against the above injury in cardiomyocyte.

Tetramethylpyrazine alleviates iron overload damage in vascular endothelium via upregulating DDAHII expression.

Iron overload causes vascular endothelium damage. It has been thought to relate excessive reactive oxygen species (ROS) generation. Tetramethylpyrazine (TMP), an active ingredient of Ligusticum chuanxiong Hort, protects various cells by inhibiting oxidative stress and cascade reaction of apoptosis. However, whether TMP can increase DDAHII activity and expression against endothelial cell damage induced by iron overload, and the protective mechanism has not been elucidated. In this study, 50 µM iron dextran and 25 µM TMP were used to co-treat HUVECs for 48 h. TMP could increase cell viability and decrease LDH activity, enhance DDAHII expression and activity, p-eNOS/eNOS ratio, NO content, and reduce ADMA level. TMP also showed a strong antioxidant activity with inhibited ROS generation and oxidative stress. Moreover, TMP attenuated mitochondrial membrane potential loss, inhibited mitochondrial permeability transition pore openness, and decreased apoptosis induced by iron overload. While mentioned above, the protective effects of TMP were abolished with the addition of pAD/DDAHII-shRNA. The effects of TMP against iron overload were similar to the positive control groups, L-arginine, a competitive substrate of ADMA, or edaravone, free radical scavenger. These results signify that TMP alleviated iron overload damage in vascular endothelium via ROS/ADMA/ DDAHII/eNOS/NO pathway.