Liproxstatin-1 alleviates ferroptosis in sevoflurane anesthesia-induced cognitive deficits of aged mice: The role oxidative stress.

In this study, we aimed to validate the hypothesis that the interplay between sevoflurane, oxidative stress and ferroptosis is crucial for the pathogenesis of sevoflurane-induced cognitive impairment in aged individuals. The mice with sevoflurane-induced cognitive impairment were used to explore the effects of sevoflurane on oxidative stress, iron homeostasis, and cognitive function in aged mice. Iron content and oxidative stress markers were analyzed in hippocampal tissue homogenates using specific assays. Additionally, the levels of iron death-related markers (Fth1 and Gpx4) were assessed by real-time PCR and Western blotting. Morris Water Maze and novel object recognition (NOR) tests were conducted to evaluate cognitive function. Sevoflurane exposure in aged mice resulted in a significant increase in iron overloading in the hippocampus, followed by a subsequent stabilization. Oxidative stress levels were elevated in the hippocampal tissue of sevoflurane-exposed mice, and a significant correlation was observed between iron death and oxidative stress. Liproxstatin-1, a ferroptosis inhibitor, effectively ameliorated the decline in memory and learning abilities induced by sevoflurane anesthesia. Liproxstatin-1 treatment reduced iron overload and oxidative stress in the hippocampal tissue of aged mice. The expression of Fth1 and Gpx4, iron death-related markers, was downregulated following Liproxstatin-1 intervention. Our findings suggest that sevoflurane anesthesia disrupts iron homeostasis, leading to increased oxidative stress and cognitive impairment in aged mice. These results highlight the potential of targeting iron-mediated processes to mitigate sevoflurane-induced cognitive impairment in the aging population.

Prognostic risk factor of major salivary gland carcinomas and survival prediction model based on random survival forests.

Salivary gland malignancies are rare and are often acompanied by poor prognoses. So, identifying the populations with risk factors and timely intervention to avoid disease progression is significant. This study provides an effective prediction model to screen the target patients and is helpful to construct a cost-effective follow-up strategy. We enrolled 249 patients diagnosed with salivary gland tumors and analyzed prognostic risk factors using Cox proportional hazard univariable and multivariable regression models. The patients' data were split into training and validation sets on a 7:3 ratio, and the random survival forest (RSF) model was established using the training sets and validated using the validation sets. The maximally selected rank statistics method was used to determine a cut point value corresponding to the most significant relation with survival. Univariable Cox regression suggested age, smoking, alcohol consumption, untreated, neural invasion, capsular invasion, skin invasion, tumors larger than 4 cm, advanced T and N stage, distant metastasis, and non-mucous cell carcinoma were risk factors for poor prognosis, and multivariable analysis suggested that female, aging, smoking, untreated, and non-mucous cell carcinoma were risk factors. The time-dependent ROC curve showed the AUC of the RSF prediction model on 1-, 2-, and 3-year survival were 0.696, 0.779, and 0.765 respectively in the validation sets. Log-rank tests suggested that the cut point 7.42 risk score calculated from the RSF was most effective in dividing patients with significantly different prognoses. The prediction model based on the RSF could effectively screen patients with poor prognoses.

Pollution Risk Assessment and Sources Analysis of Heavy Metal in Soil from Bamboo Shoots.

In order to investigate the pollution situation and sources analysis of heavy metals in bamboo shoot soil in Guangdong Province, a total of 175 soil samples were collected at 46 sites. Atomic fluorescence spectrophotometer and inductively coupled plasma mass spectrometry were used to determine the content of five heavy metals: lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), and chromium (Cr). In addition, the soil environmental quality was evaluated through different index methods, including single-factor pollution, Nemeiro comprehensive pollution, geoaccumulation, and potential ecological risk. Furthermore, the correlation coefficients were also discussed. The results showed that the soils collected were acidic or slight alkaline. The maximum content of Pb and As from some areas exceeded the standard limit value. The coefficient of variation value from six areas exceeded 100%. The index method mentioned above confirmed that the soil within study areas was divided into three pollution levels: no, slightly, and mild. Additionally, there was a very significant correlation between pH and Pb, Hg; the correlation between heavy metal As and Pb, Cr also reached a very significant level. The principal component analysis results show that PC1 accounts for 39.60% of the total variance, which includes Pb, Cd, and As. PC2 mainly includes Hg and Cr.

Nodakenetin Alleviates Inflammatory Pain Hypersensitivity by Suppressing NF-κB Signal Pathway.

BACKGROUND: Inflammatory pain mediated by nuclear factor kappa-B (NF-κB) signal pathway has become an increasingly important clinical issue in the last decade. As a potent antioxidant, Nodakenetin has been shown to have a prominent inhibitory effect on inflammation. However, the therapeutic effects and underlying pharmacological mechanisms of Nodakenetin for inflammatory pain remain unclear. METHODS: Intraplanar injection of complete Freund's adjuvant (CFA) was used to establish a model of chronic inflammation pain in C57BL/6 mice. The chronic neuropathic pain model was conducted by the sciatic nerve ligation surgery. QRT-PCR was performed to estimate the RNA levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). Western blot was used to demonstrated the protein levels of phospho-IkappaBα (IκBα), p50, and p65 in HEK293T cells. RESULTS: The bioactive components of the traditional Chinese medicine Notopterygium forbesii boiss mainly include Nodakenetin, isoimperatorin, and pregnenolone. Nodakenetin significantly alleviated CFA-induced inflammatory pain but showed no significant therapeutic effect on surgically induced neuralgia in a mouse model. In contrast, isoimperatorin and pregnenolone did not relieve CFA-induced inflammatory pain. Mechanistically, Nodakenetin inhibited IL-1ß-induced activation of the NF-κB pathway and phosphorylation of IκBα in HEK293T cells. Furthermore, Nodakenetin treatment suppressed the expression of IL-6, TNF-α, and IL-1ß in mouse bone marrow-derived macrophages. CONCLUSION: Nodakenetin alleviates inflammatory pain induced by CFA injection in vivo and modulates NF-κB signal pathway in vitro.

Polycyclic Phenol Derivatives from the Leaves of Spermacoce latifolia and Their Antibacterial and α-Glucosidase Inhibitory Activity.

Three new polycyclic phenol derivatives, 2-acetyl-4-hydroxy-6H-furo [2,3-g]chromen-6-one (1), 2-(1',2'-dihydroxypropan-2'-yl)-4-hydroxy-6H-furo [2,3-g][1]benzopyran-6-one (2) and 3,8,10-trihydroxy-4,9-dimethoxy-6H-benzo[c]chromen-6-one (8), along with seven known ones (3-7, 9 and 10) were isolated for the first time from the leaves of Spermacoce latifolia. Their structures were determined by spectroscopic analysis and comparison with literature-reported data. These compounds were tested for their in vitro antibacterial activity against four Gram-(+) bacteria: Staphyloccocus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus (BC), Bacillus subtilis (BS), and the Gram-(-) bacterium Escherichia coli. Compounds 1, 2, 5 and 8 showed antibacterial activity toward SA, BC and BS with MIC values ranging from 7.8 to 62.5 µg/mL, but they were inactive to MRSA. Compound 4 not only showed the best antibacterial activity against SA, BC and BS, but it further displayed significant antibacterial activity against MRSA (MIC 1.95 µg/mL) even stronger than vancomycin (MIC 3.9 µg/mL). No compounds showed inhibitory activity toward E. coli. Further bioassay indicated that compounds 1, 4, 5, 6, 8 and 9 showed in vitro α-glucosidase inhibitory activity, among which compound 9 displayed the best α-glucosidase inhibitory activity with IC50 value (0.026 mM) about 15-fold stronger than the reference compound acarbose (IC50 0.408 mM). These results suggested that compounds 4, 8 and 9 were potentially highly valuable compounds worthy of consideration to be further developed as an effective anti-MRSA agent or effective α-glucosidase inhibitors, respectively. In addition, the obtained data also supported that S. latifolia was rich in structurally diverse bioactive compounds worthy of further investigation, at least in searching for potential antibiotics and α-glucosidase inhibitors.

The Role of Gut Microbiota in Mice With Bile Duct Ligation-Evoked Cholestatic Liver Disease-Related Cognitive Dysfunction.

The pathogenesis of Hepatic Encephalopathy (HE) is complex and multifactorial. The development of metagenomics sequencing technology led to show the significant role of gut microbiota in the pathogenesis of cognitive dysfunction, which paved the way for further research in this field. However, it is unknown whether gut microbiota plays a role in bile duct ligation (BDL)-evoked cholestatic liver disease-related cognitive dysfunction. The aim of this investigation is to assess BDL mice induced cognitive dysfunction and meanwhile to delineate the alteration of gut microbiota in cognitive dysfunction mice, which may underline the role of gut microbiota in BDL mice induced cognitive dysfunction. Our study was carried out in male C57BL/6 J mice with bile duct ligation. The liver functions were assessed via different biochemical markers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), and total bile acid (TBA)] and a histopathological examination of the liver tissue. We used the novel object recognition test (NORT) to assess cognitive dysfunction. And BDL mice were divided into BDL with cognitive dysfunction (BDL-CD) or BDL without cognitive dysfunction (BDL-NCD groups) by the result of hierarchical cluster analysis of NORT. Then, 16S ribosomal RNA (rRNA) gene sequencing was used to compare the gut bacterial composition between BDL-CD and BDL-NCD groups. According to our results, we concluded that bile duct ligation can significantly change the gut microbiota composition, and Bacteroides fragilis, Bacteroides ovatus V975, and Bacteroides thetaiotaomicron play a vital role in BDL-evoked cholestatic liver disease-related cognitive dysfunction.

Upregulated circRAD18 promotes tumor progression by reprogramming glucose metabolism in papillary thyroid cancer.

BACKGROUND: By regulating complex functional processes, circRNAs are crucial in the development of different cancers. Nevertheless, most circRNAs in papillary thyroid cancer metabolic reprogramming remain unknown. METHODS: The expression of circRNA was assessed by qRT-PCR in papillary thyroid cancer tissues and cell lines. Cell proliferation and glucose intake experiments were performed by certain kit. Transwell assays and wound healing assays were performed to investigate the function of circRNA in metastasis. In addition, a serious of molecular experiments were conducted to determine the exact mechanism of circRAD18. Luciferase reporter and RNA immunoprecipitation assay were conducted to determine the molecular interaction between circRNA and miRNA. RESULTS: We characterized circRAD18 as a significantly upregulated circRNA in papillary thyroid tissues and cell lines and found its downregulation could inhibit the growth and metastasis ability of papillary thyroid cancer. Interestingly, we found that circRAD18 was involved in glucose metabolism reprogramming of papillary thyroid cancer, and its silence could remarkably inhibit cell glucose uptake and lactate production in papillary thyroid cancer cells. Inhibition of circRAD18 could decrease the expression level of PDK1 protein by sponging miR-516b. CONCLUSIONS: This study verified the novel function of the circRAD18-miR-516b-PDK1 axis in papillary thyroid cancer metabolic reprogramming progression, which has potential to be a novel therapeutic target.

Circular RNA circKIF4A facilitates the malignant progression and suppresses ferroptosis by sponging miR-1231 and upregulating GPX4 in papillary thyroid cancer.

Circular RNAs (circRNAs) are one type of non-coding RNA. They act as important role in regulating various biological processes in the malignant progression. But we don't clearly know the specific mechanism of the majority circRNAs in papillary thyroid tumor progression. In the current study, we explored circKIF4A and the result showed that it had high expression in papillary thyroid cancer. The functions of circKIF4A were explored by CCK-8, transwell, and mouse xenograft experiments. Knockdown of circKIF4A could suppress papillary thyroid cell growth and migration. In addition, RIP assays and dual luciferase vector reporter assays were further conducted. Our consequence showed circKIF4A facilitated the malignant progress of papillary thyroid tumor by sponging miR-1231 and upregulating GPX4 expression. In conclusion, our study proved that circKIF4A-miR-1231-GPX4 axis played a vital role in cancer proliferation and ferroptosis by competing endogenous RNAs. Therefore, targeting circKIF4A is very likely to be a potential method for treatment of papillary thyroid cancer in the future.

Inhibiting PDE7A Enhances the Protective Effects of Neural Stem Cells on Neurodegeneration and Memory Deficits in Sevoflurane-Exposed Mice.

Sevoflurane is widely used in general anesthesia, especially for children. However, prolonged exposure to sevoflurane is reported to be associated with adverse effects on the development of brain in infant monkey. Neural stem cells (NSCs), with potent proliferation, differentiation, and renewing ability, provide an encouraging tool for basic research and clinical therapies for neurodegenerative diseases. We aim to explore the functional effects of injecting NSCs with phosphodiesterase 7A (PDE7A) knock-down in infant mice exposed to sevoflurane. The effects of PDE7A in NSCs proliferation and differentiation were determined by cell counting kit-8 (CCK-8) assay and differentiation-related gene expression assay, respectively. The effects of NSCs with modified PDE7A on mice's long-term memory and learning ability were assessed by behavioral assays. Our data demonstrated that depleting PDE7A promoted, whereas forcing PDE7A suppressed the activation of cAMP/cAMP-response element binding protein (CREB) signaling as well as cell proliferation and neuronal differentiation of NSCs. Inhibition of PDE7A in NSCs exhibited profound improved effects on long-term memory and learning ability of mice exposed to sevoflurane. Our results for the first time show that knock-down of PDE7A improves the neurogenesis of NSCs in vitro and in vivo, and is beneficial for alleviating sevoflurane-induced brain damage in infant mice.

Effects of transfusion load and suction pressure on renal function in intraoperative salvage autotransfusion.

Although some investigations have been performed to determine the effects of transfusion load and suction pressure on renal function during intraoperative salvage autotransfusion, the precise threshold is still undetermined. A total of 625 patients undergoing surgery with the Continuous AutoTransfusion System (CATSplus) were enrolled and divided into groups according to the utilized suction pressure and transfusion volume. Plasma free hemoglobin (FHB) and creatinine clearance (CCr) were assayed to indicate the renal function. Both 0.03 MPa suction (≥4-unit load) and >5 units transfusion changed the levels of FHB and CCr significantly when measured 24 h post-operation compared to pre-operation. Under 0.02 MPa suction (≥4-unit load), the alteration of FHB and CCr returned to normal after 24 h. Under 3 units transfusion, the levels of FHB and CCr at 6 and 12 h post-operation changed significantly compared to pre-operation (P<0.05 or P<0.01, respectively), and this alteration could be restored to normal at 72 h post-operation. After an exhaustive investigation, less than 4 units transfusion and less than 0.03 MPa suction pressure are recommended for intraoperative salvage autotransfusion.

Ultrasound-guided stellate ganglion block alleviates stress responses and promotes recovery of gastrointestinal function in patients.

BACKGROUND: This study aimed to investigate the effect of preoperative ultrasound-guided stellate ganglion block (SGB) on the perioperative stress responses and gastrointestinal functions of patients undergoing laparoscopic colorectal cancer surgery. METHODS: A total of 60 colorectal cancer patients were enrolled in study and were randomized to be treated with or without SGB therapy. In the SGB group, patients were injected with 7 mL 0.5% ropivacaine in stellate ganglion under ultrasound guidance before anesthesia. Mean artery pressure (MAP), heart rate (HR), recovery of bowel sound and first exhaust, as well as levels of motilin, gastrin, norepinephrine, cortisol, interleukin-6 (IL-6) and C-reactive protein (CRP) were recorded at various time points. RESULTS: 26 patients in the SGB group and 27 patients in the control group were analyzed. No significant differences in MAP or HR were observed between the two groups before, during and after the surgery. SGB promoted recovery of gastrointestinal functions, as evidenced by earlier recovery of bowel sound and first exhaust, as well as increased motilin and gastrin levels. SGB also attenuated stress responses, as shown in reduced norepinephrine, cortisol, IL-6 and CRP levels. CONCLUSIONS: SGB promotes the recovery of gastrointestinal functions and reduces stress responses of colorectal patients undergoing laparoscopic colorectal cancer surgery.

Effects of transfusion load and suction pressure on renal function in intraoperative salvage autotransfusion

Although some investigations have been performed to determine the effects of transfusion load and suction pressure on renal function during intraoperative salvage autotransfusion, the precise threshold is still undetermined. A total of 625 patients undergoing surgery with the Continuous AutoTransfusion System (CATSplus) were enrolled and divided into groups according to the utilized suction pressure and transfusion volume. Plasma free hemoglobin (FHB) and creatinine clearance (CCr) were assayed to indicate the renal function. Both 0.03 MPa suction (≥4-unit load) and >5 units transfusion changed the levels of FHB and CCr significantly when measured 24 h post-operation compared to pre-operation. Under 0.02 MPa suction (≥4-unit load), the alteration of FHB and CCr returned to normal after 24 h. Under 3 units transfusion, the levels of FHB and CCr at 6 and 12 h post-operation changed significantly compared to pre-operation (P<0.05 or P<0.01, respectively), and this alteration could be restored to normal at 72 h post-operation. After an exhaustive investigation, less than 4 units transfusion and less than 0.03 MPa suction pressure are recommended for intraoperative salvage autotransfusion.

Specific Patterns of Spinal Metabolite Ratio Underlying α-Me-5-HT-evoked Pruritus Compared with Compound 48/80 Based on Proton Nuclear Magnetic Resonance Spectroscopy.

Mechanisms of pruritus are implicated in the dysregulation of the metabolites in the spinal cord. We investigated pruritus behavioral testing in three groups of young adult male C57Bl/6 mice, including one group treated with normal saline, while the other groups intradermally injected with α-Me-5-HT (histamine-independent pruritogen), compound 48/80 (histamine-dependent pruritogen) at the nape skin of the neck, respectively. Proton nuclear magnetic resonance spectroscopy (MRS) was used to compare spinal metabolites from the vertebral cervical among three groups, and to study the association of spinal metabolite ratio and pruritus intensity. The MRS-measured N-acetylaspartate-to-myoinositol ratio (NAA/Ins) was significantly correlated with the number of scratches between normal saline group and 48/80 group or α-Me-5-HT group (both P<0.0001), indicating that NAA/Ins may be a robust surrogate marker of histamine-independent/dependent pruritogen. There was significant difference in Glu/Ins between normal saline group and 48/80 group (P=0.017), indicating that Glu/Ins may be a surrogate marker of histamine-dependent pruritogen, while GABA/Ins was highly significantly different between normal saline group and α-Me-5-HT group (P=0.008), suggesting that GABA/Ins may be a surrogate marker of histamine-independent pruritogen. MRS may reflect the extent of pruritus intensity elicited by α-Me-5-HT and compound 48/80 with sensitivity similar to the number of scratches, and above potential markers need to be further validated in pre-clinical and clinical treatment trials.

PDE-7 Inhibitor BRL-50481 Reduces Neurodegeneration and Long-Term Memory Deficits in Mice Following Sevoflurane Exposure.

Sevoflurane, one of the most commonly used anesthetic agents, has been demonstrated to induce widespread neurodegeneration in the developing brain. We aimed to evaluate the protective effects of a PDE-7 inhibitor (BRL-50481) against the neurotoxic effects of sevoflurane on the developing nervous system. Spatial learning and memory in sevoflurane-treated mice were examined using the Morris water maze test, and neuroprotective effects of PDE-7 inhibitor (BRL-50481) against sevoflurane-induced impairments were evaluated. Our results showed that sevoflurane treatment markedly induced neurodegeneration and impaired long-term memory in neonatal mice. Notably, BRL-50481 coadministration could significantly attenuate sevoflurane-induced learning and memory defects, prevent deterioration of recognition memory, and protect against neuron apoptosis. Mechanistically, BRL-50481 administration suppressed sevoflurane-induced neurodegenerative disorders through restoring cAMP and activating cAMP/CREB signaling in the hippocampus. PDE7 inhibitor may be a potential therapeutic agent for sevoflurane-induced neurodegeneration and long-term memory deficits.

Identification of lncRNA and mRNA expression profiles in rat spinal cords at various time­points following cardiac ischemia/reperfusion.

The identification of the expression patterns of long non­coding RNAs (lncRNAs) and mRNAs in the spinal cord under normal and cardiac ischemia/reperfusion (I/R) conditions is essential for understanding the genetic mechanisms underlying the pathogenesis of cardiac I/R injury. The present study used high­throughput RNA sequencing to investigate differential gene and lncRNA expression patterns in the spinal cords of rats during I/R­induced cardiac injury. Male Sprague Dawley rats were assigned to the following groups: i) Control; ii) 2 h (2 h post­reperfusion); and iii)v0.5 h (0.5 h post­reperfusion). Further mRNA/lncRNA microarray analysis revealed that the expression profiles of lncRNA and mRNA in the spinal cords differed markedly between the control and 2 h groups, and in total 7,980 differentially expressed (>2­fold) lncRNAs (234 upregulated, 7,746 downregulated) and 3,428 mRNAs (767 upregulated, 2,661 downregulated) were identified. Reverse transcription­quantitative polymerase chain reaction analysis was performed to determine the expression patterns of several lncRNAs. The results indicated that the expression levels of lncRNA NONRATT025386 were significantly upregulated in the 2 and 0.5 h groups when compared with those in the control group, whereas the expression levels of NONRATT016113, NONRATT018298 and NONRATT018300 were elevated in the 2 h group compared with those in the control group; however, there was no statistically significant difference between the 0.5 h and control groups. Furthermore, the expression of lncRNA NONRATT002188 was significantly downregulated in the 0.5 and 2 h groups when compared with the control group. The present study determined the expression pattern of lncRNAs and mRNAs in rat spinal cords during cardiac I/R. It was suggested that lncRNAs and mRNAs from spinal cords may be novel therapeutic targets for the treatment of I/R­induced cardiac injury.

Prognostic value of primary tumor surgery in de novo stage IV breast cancer patients with different metastatic burdens: a propensity score-matched and population-based study.

BACKGROUND: Whether primary tumor surgery should be performed in breast cancer patients with metastatic disease at diagnosis has been debated for decades. This study aims to evaluate the value of primary tumor surgery with respect to the mortality of patients with de novo stage IV breast cancer and to define the heterogeneity of this population. METHODS: De novo stage IV patients from the Surveillance, Epidemiology and End Results database (SEER) from 2010 to 2015 were included in our study. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to achieve balanced baseline characteristics. The effect of surgery was assessed by Kaplan-Meier curves and Cox regression models. RESULTS: Of the 11,684 patients eligible for analysis, 3,730 (31.92%) received primary tumor surgery. Multivariate Cox regression in the PSM cohort revealed that surgery was associated with better outcomes than those in the nonsurgery group in terms of overall survival (OS) [hazard ratio (HR): 0.51; 95% CI: 0.48-0.55; P<0.001] and breast cancer-specific survival (BCSS) (HR: 0.51; 95% CI: 0.47-0.55; P<0.001). IPTW analysis yielded similar results. In a subgroup analysis, surgery was associated with better survival in all subtypes with low metastatic burdens (≤2 metastatic sites), but triple-negative breast cancer with a high metastatic burden (>2 metastatic sites) did not benefit from surgery (HR: 0.78; 95% CI: 0.31-1.97, P=0.596 and 0.78, 95% CI: 0.31-1.97, P=0.596 for OS and BCSS, respectively). CONCLUSIONS: Primary tumor surgery significantly prolonged the survival of patients with de novo stage IV breast cancer. However, triple-negative breast cancer patients with more than two metastatic sites may not benefit from surgery.

The lymph node ratio as an independent prognostic factor for node-positive triple-negative breast cancer.

BACKGROUND: We aimed to evaluate the prognostic value of the lymph node ratio (LNR) in patients with axillary lymph node-positive triple-negative breast cancer (TNBC). METHODS: The prognostic efficacy was investigated in the first cohort from the Surveillance, Epidemiology, and End Results (SEER) dataset (n=4114) and was further validated in an independent cohort from Fudan University Shanghai Cancer Center (n=417). Patients were classified into low-, medium- and high-risk LNR groups. RESULTS: Multivariate analysis revealed that the LNR was an independent predictor of overall survival (hazard ratio (HR) for high-risk LNR: 3.24; 95% confidence interval (CI): 2.56 to 4.09) and breast cancer-specific survival (HR for high-risk LNR: 3.57; 95% CI: 2.76 to 4.62) in the SEER population and also for disease-free survival (HR for high-risk LNR: 4.29; 95% CI: 2.24-8.21) in the validation population. Subgroup analysis revealed that patient classification according to the LNR could discriminate among groups of patients with different survival rates based on pathological nodal (pN) staging. CONCLUSION: The LNR shows potential for use as an additional prognostic factor for TNBC patients with positive lymph node involvement. Considering the heterogeneity of TNBC, use of the LNR might allow for optimization of the pN staging system and should be considered when making treatment decisions.

Melanocortin-4 receptor expression in autonomic circuitry involved in gastric function.

Several studies have shown that CNS provides the regulation of gastric functions. Recent evidence indicated that the activation of melanocortin 4 receptors (MC4R) in brain nuclei played an important role in modulating gastric activity. This study was designed to assess whether MC4R signaling existed in autonomic circuitry modulated the activity of stomach by a virally mediated transsynaptic tracing study. Pseudorabies virus (PRV)-614 was injected into the ventral stomach wall in adult male MC4R-green fluorescent protein (GFP) transgenic mice (n = 5). After a survival time of 5 days, the mice were assigned to humanely sacrifice, and spinal cords and caudal brainstem were removed and sectioned, and processed for PRV-614 visualization. Neurons involved in the efferent control of the stomach were identified following visualization of PRV-614 retrograde tracing. The neurochemical phenotype of MC4R-GFP-positive neurons was identified using fluorescence immunocytochemical labeling. PRV-614/MC4R-GFP dual labeled neurons were detected in spinal IML and the dorsal motor nucleus of the vagus nerve (DMV). Our findings support the hypothesis that MC4R signaling in autonomic circuitry may participate in the modulation of gastric activity by the melanocortinergic-sympathetic pathway or melanocortinergic-parasympathetic pathway.