Global disease burden linked to diet high in red meat and colorectal cancer from 1990 to 2019 and its prediction up to 2030.

Background: Numerous studies have already identified an association between excessive consumption of red meat and colorectal cancer (CRC). However, there has been a lack of detailed understanding regarding the disease burden linked to diet high in red meat and CRC. Objective: We aim to offer evidence-based guidance for developing effective strategies that can mitigate the elevated CRC burden in certain countries. Methods: We used the data from the Global Burden of Disease (GBD) Study 2019 to evaluate global, regional, and national mortality rates and disability-adjusted Life years (DALYs) related to diet high in red meat. We also considered factors such as sex, age, the socio-demographic index (SDI), and evaluated the cross-national inequalities. Furthermore, we utilized DALYs data from 204 countries and regions to measure cross-country inequalities of CRC by calculating the slope index of inequality and concentration index as standard indicators of absolute and relative inequalities. Discussion: The results show that globally, the age-standardized mortality rate (ASMR) and age-standardized disability adjusted life year rate (ASDR) related to CRC due to diet high in red meat have decreased, with estimated annual percent change (EAPCs) of -0.32% (95% CI -0.37 to -0.28) and-0.18% (95% CI -0.25 to -0.11). Notably, the burden was higher among males and the elderly. The slope index of inequality rose from 22.0 (95% CI 18.1 to 25.9) in 1990 to 32.9 (95% CI 28.3 to 37.5) in 2019 and the concentration index fell from 59.5 (95% CI 46.4 to 72.6) in 1990 to 48.9 (95% CI 34.6 to 63.1) in 2019. Also, according to our projections, global ASDR and ASMR might tend to increase up to 2030. Conclusion: ASMR and ASDR for CRC associated with high red meat diets declined globally from 1990 to 2019, but the absolute number of cases is still rising, with men and the elderly being more affected. CRC associated with diets high in red meat exhibits significant income inequality, placing a disproportionate burden on wealthier countries. Moreover, according to our projections, ASMR and ASDR are likely to increase globally by 2030. In order to address this intractable disease problem, understanding changes in global and regional epidemiologic trends is critical for policy makers and others.

Gut microbiota regulates hepatic ischemia-reperfusion injury-induced cognitive dysfunction via the HDAC2-ACSS2 axis in mice.

AIMS: Hepatic ischemia-reperfusion injury (HIRI) resulting from hepatic inflow occlusion, which is a common procedure in liver surgery is inevitable. Previous research has confirmed that the cognitive dysfunction induced by HIRI is closely related to dysbiosis of the gut microbiota. This research aims to investigate the mechanisms underlying this complication. METHODS: C57BL/6 mice underwent hepatic ischemia experimentally through the occlusion of the left hepatic artery and portal vein. To assess the HDAC2-ACSS2 axis, gut microbiota transplantation. Enzyme-linked immunosorbent assay and LC/MS short-chain fatty acid detection were utilized. RESULTS: The findings indicated a notable decline in ACSS2 expression in the hippocampus of mice experiencing hepatic ischemia-reperfusion injury, emphasizing the compromised acetate metabolism in this particular area. Furthermore, the cognitive impairment phenotype and the dysregulation of the HDAC2-ACSS2 axis could also be transmitted to germ-free mice via fecal microbial transplantation. Enzyme-linked immunosorbent assay revealed reduced Acetyl-coenzyme A (acetyl-CoA) and Acetylated lysine levels in the hippocampus. CONCLUSION: These findings suggest that acetate metabolism is impaired in the hippocampus of HIRI-induced cognitive impairment mice and related to dysbiosis, leading to compromised histone acetylation.

Neurogenesis manifestations of solid tumor and tracer imaging studies: a narrative review.

With the emergence of the scientific research field of tumor microenvironment, the idea that tumor growth and propagation cannot be separated from the tumor microenvironment has become common. The autonomic nervous system is involved in the whole process of growth and development of the organism, and it is undeniable that the tumor microenvironment is equally regulated by both the autonomic nervous system and the immune system. Our research focused on the cancer-nerve crosstalk process and revealed the regulatory mechanisms between the autonomic nervous system and prostate, gastric, pancreatic ductal and breast cancers, mainly elucidating that (1) the release of neurotransmitters and their receptors by autonomic nerves may be important for solid tumor progression, and (2) in combination with the latest targeted small molecule imaging technology, we summarized the biological pathways related to neurotransmitters as small molecule tracers to track solid tumor progression. This research focused on combining targeted small molecules and imaging techniques to observe sympathetic and parasympathetic processes that promote or inhibit cancer development, providing new potential therapeutic targets for prostate, gastric, pancreatic ductal and breast cancers. It also provided cutting-edge research evidence for the development of biological small molecule drugs and targeted tracers in cancer therapy.

Gut microbiota regulates circadian oscillation in hepatic ischemia-reperfusion injury-induced cognitive impairment by interfering with hippocampal lipid metabolism in mice.

BACKGROUND: Hepatic ischemia-reperfusion injury (HIRI) is a common complication of liver surgery, which can lead to extrahepatic metabolic disorders, such as cognitive impairment. Recent observations have emphasized the critical effects of gut microbial metabolites in regulating the development of liver injury. Herein, we investigated the potential contribution of gut microbiota to HIRI-related cognitive impairment. METHODS: HIRI murine models were established by ischemia-reperfusion surgery in the morning (ZT0, 08:00) and evening (ZT12, 20:00), respectively. Antibiotic-induced pseudo-germ-free mice were gavaged with fecal bacteria of the HIRI models. Behavioral test was used to assess cognitive function. 16S rRNA gene sequencing and metabolomics were used for microbial and hippocampal analysis. RESULTS: Our results established that cognitive impairment caused by HIRI underwent diurnal oscillations; HIRI mice performed poorly on the Y-maze test and the novel object preference test when surgery occurred in the evening compared with the morning. In addition, fecal microbiota transplantation (FMT) from the ZT12-HIRI was demonstrated to induce cognitive impairment behavior. The specific composition and metabolites of gut microbiota were analyzed between the ZT0-HIRI and ZT12-HIRI, and bioinformatic analysis showed that the differential fecal metabolites were significantly enriched in lipid metabolism pathways. After FMT, the hippocampal lipid metabolome between the P-ZT0-HIRI and P-ZT12-HIRI groups was analyzed to reveal a series of lipid molecules with significant differences. CONCLUSIONS: Our findings indicate that gut microbiota are involved in circadian differences of HIRI-related cognitive impairment by affecting hippocampal lipid metabolism.

Contribution of preoperative gut microbiota in postoperative neurocognitive dysfunction in elderly patients undergoing orthopedic surgery.

Objective: To investigate the role of gut microbiota and metabolites in POCD in elderly orthopedic patients, and screen the preoperative diagnostic indicators of gut microbiota in elderly POCD. Method: 40 elderly patients undergoing orthopedic surgery were enrolled and divided into Control group and POCD group following neuropsychological assessments. Gut microbiota was determined by 16S rRNA MiSeq sequencing, and metabolomics of GC-MS and LC-MS was used to screen the differential metabolites. We then analyzed the pathways enriched by metabolites. Result: There was no difference in alpha or beta diversity between Control group and POCD group. There were significant differences in 39 ASV and 20 genera bacterium in the relative abundance. Significant diagnostic efficiency analyzed by the ROC curves were found in 6 genera bacterium. Differential metabolites in the two groups including acetic acid, arachidic acid, pyrophosphate etc. were screened out and enriched to certain metabolic pathways which impacted the cognition function profoundly. Conclusion: Gut microbiota disorders exist preoperatively in the elderly POCD patients, by which there could be a chance to predict the susceptible population. Clinical Trial Registration: [http://www.chictr.org.cn/edit.aspx?pid=133843&htm=4], identifier [ChiCTR2100051162].

The Role of Gut Microbiota and Circadian Rhythm Oscillation of Hepatic Ischemia-Reperfusion Injury in Diabetic Mice.

Circadian rhythm oscillation and the gut microbiota play important roles in several physiological functions and pathology regulations. In this study, we aimed to elucidate the characteristics of diabetic hepatic ischemia-reperfusion injury (HIRI) and the role of the intestinal microbiota in diabetic mice with HIRI. Hepatic ischemia-reperfusion injury surgery was performed at ZT0 or ZT12. The liver pathological score and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed to evaluate liver injury. We conducted an FMT experiment to examine the role of intestinal microbiota in diabetic mice with HIRI. The 16S rRNA gene sequencing of fecal samples was performed for microbial analysis. Our results showed that hyperglycemia aggravated HIRI in diabetic mice, but there was no diurnal variation seen in diabetic HIRI. We also demonstrated that there were significant alterations in the gut microbiota composition between the diabetic and control mice and that gut microbiota transplantation from diabetic mice had obvious harmful effects on HIRI. These findings provide some useful information for the future research of diabetic mice with HIRI.

A novel technology for in vivo detection of cell type-specific neural connection with AQP1-encoding rAAV2-retro vector and metal-free MRI.

A mammalian brain contains numerous neurons with distinct cell types for complex neural circuits. Virus-based circuit tracing tools are powerful in tracking the interaction among the different brain regions. However, detecting brain-wide neural networks in vivo remains challenging since most viral tracing systems rely on postmortem optical imaging. We developed a novel approach that enables in vivo detection of brain-wide neural connections based on metal-free magnetic resonance imaging (MRI). The recombinant adeno-associated virus (rAAV) with retrograde ability, the rAAV2-retro, encoding the human water channel aquaporin 1 (AQP1) MRI reporter gene was generated to label neural connections. The mouse was micro-injected with the virus at the Caudate Putamen (CPU) region and subjected to detection with Diffusion-weighted MRI (DWI). The prominent structure of the CPU-connected network was clearly defined. In combination with a Cre-loxP system, rAAV2-retro expressing Cre-dependent AQP1 provides a CPU-connected network of specific type neurons. Here, we established a sensitive, metal-free MRI-based strategy for in vivo detection of cell type-specific neural connections in the whole brain, which could visualize the dynamic changes of neural networks in rodents and potentially in non-human primates.

Superior cervical ganglionectomy alters gut microbiota in rats.

The diversity and complexity of sympathetic function highlight the importance of fundamental research. Little is known about the interaction of superior cervical sympathetic ganglion (SCG) and gut microbiota. In this study, the engagement of the sympathetic ganglia with gut microbiota was investigated. Bilateral superior cervical ganglionectomy (SCGx) significantly altered the microbiota composition in rats 14 days post-surgery, and these microbiotas may participate in several biological pathways in the host, suggesting the vital role of the cervical sympathetic ganglion in regulating the microbiome-brain axis, and further confirming that the sympathetic nervous system (SNS) regulates the microbiome-brain axis.

The Preventive Effect of Cardiac Sympathetic Denervation Induced by 6-OHDA on Myocardial Ischemia-Reperfusion Injury: The Changes of lncRNA/circRNAs-miRNA-mRNA Network of the Upper Thoracic Spinal Cord in Rats.

In this study, we investigated whether chemical 6-hydroxydopamine (6-OHDA) stimuli caused cardiac sympathetic denervation (SD), and we analyzed gene expression profiles to determine the changes in the lncRNA/circRNAs-miRNA-mRNA network in the affected spinal cord segments to identify putative target genes and molecular pathways in rats with myocardial ischemia-reperfusion injury (MIRI). Our results showed that cardiac sympathetic denervation induced by 6-OHDA alleviated MIRI. Compared with the ischemia reperfusion (IR, MIRI model) group, there were 148 upregulated and 51 downregulated mRNAs, 165 upregulated and 168 downregulated lncRNAs, 70 upregulated and 52 downregulated circRNAs, and 12 upregulated and 11 downregulated miRNAs in the upper thoracic spinal cord of the SD-IR group. Furthermore, we found that the differential genes related to cellular components were mainly enriched in extracellular and cortical cytoskeleton, and molecular functions were mainly enriched in chemokine activity. Pathway analysis showed that the differentially expressed genes were mainly related to the interaction of cytokines and cytokine receptors, sodium ion reabsorption, cysteine and methionine metabolism, mucoglycan biosynthesis, cGMP-PKG signaling pathway, and MAPK signaling pathway. In conclusion, the lncRNA/circRNAs-miRNA-mRNA networks in the upper thoracic spinal cord play an important role in the preventive effect of cardiac sympathetic denervation induced by 6-OHDA on MIRI, which offers new insights into the pathogenesis of MIRI and provides new targets for MIRI.

Neurochemical alterations of different cerebral regions in rats with myocardial ischemia-reperfusion injury based on proton nuclear magnetic spectroscopy analysis.

BACKGROUND: Recent studies have demonstrated a complex and dynamic neural crosstalk between the heart and brain. A heart-brain interaction has been described regarding cardiac ischemia, but the cerebral metabolic mechanisms involved are unknown. METHODS: Male Sprague Dawley rats were randomly allocated into 2 groups: those receiving myocardial ischemia-reperfusion surgery (IR group, n =10) and surgical controls (Con group, n=10). These patterns of metabolic abnormalities in different brain regions were assessed using proton magnetic resonance spectroscopy (PMRS). RESULTS: Results assessed by echocardiography showed resultant cardiac dysfunction following heart ischemia-reperfusion. Compared with the control group, the altered metabolites in the IR group were taurine and choline, and differences mainly occurred in the thalamus and brainstem. CONCLUSIONS: Alterations in cerebral taurine and choline are important findings offering new avenues to explore neuroprotective strategies for myocardial ischemia-reperfusion injury. These results provide preliminary evidence for understanding the cerebral metabolic process underlying myocardial ischemia-reperfusion injury in rats.

Regional Metabolic Patterns of Abnormal Postoperative Behavioral Performance in Aged Mice Assessed by 1H-NMR Dynamic Mapping Method.

Abnormal postoperative neurobehavioral performance (APNP) is a common phenomenon in the early postoperative period. The disturbed homeostatic status of metabolites in the brain after anesthesia and surgery might make a significant contribution to APNP. The dynamic changes of metabolites in different brain regions after anesthesia and surgery, as well as their potential association with APNP are still not well understood. Here, we used a battery of behavioral tests to assess the effects of laparotomy under isoflurane anesthesia in aged mice, and investigated the metabolites in 12 different sub-regions of the brain at different time points using proton nuclear magnetic resonance (1H-NMR) spectroscopy. The abnormal neurobehavioral performance occurred at 6 h and/or 9 h, and recovered at 24 h after anesthesia/surgery. Compared with the control group, the altered metabolite of the model group at 6 h was aspartate (Asp), and the difference was mainly displayed in the cortex; while significant changes at 9 h occurred predominantly in the cortex and hippocampus, and the corresponding metabolites were Asp and glutamate (Glu). All changes returned to baseline at 24 h. The altered metabolic changes could have occurred as a result of the acute APNP, and the metabolites Asp and Glu in the cortex and hippocampus could provide preliminary evidence for understanding the APNP process.

Altered expression of itch­related mediators in the lower cervical spinal cord in mouse models of two types of chronic itch.

In this study, we focused on several itch­related molecules and receptors in the spinal cord with the goal of clarifying the specific mediators that regulate itch sensation. We investigated the involvement of serotonin receptors, opioid receptors, glia cell markers and chemokines (ligands and receptors) in models of acetone/ether/water (AEW)­ and diphenylcyclopropenone (DCP)­induced chronic itch. Using reverse transcription­quantitative polymerase chain reaction, we examined the expression profiles of these mediators in the lower cervical spinal cord (C5­8) of two models of chronic itch. We found that the gene expression levels of opioid receptor mu 1 (Oprm1), 5­hydroxytryptamine receptor 1A (Htr1a) and 5­hydroxytryptamine receptor 6 (Htr6) were upregulated. Among the chemokines, the expression levels of C­C motif chemokine ligand (Ccl)21, Cxcl3 and Cxcl16 and their receptors, Ccr7, Cxcr2 and Cxcr6, were simultaneously upregulated in the spinal cords of the mice in both models of chronic itch. By contrast, the expression levels of Ccl2, Ccl3, Ccl4 and Ccl22 were downregulated. These findings indicate that multiple mediators, such as chemokines in the spinal cord, are altered and may be central candidates in further research into the mechanisms involved in the development of chronic itch.

Awake tracheal intubation using combination of an Airtraq® optical laryngoscope with smartphone and video flexible endoscope: a case report.

A patient with obvious difficult airway who was received awake tracheal intubation using combination of an Airtraq® optical laryngoscope with smartphone and video flexible endoscope posted for elective surgery of tonsillectomy for OSAHS was reported. Our experiences strongly indicate that fully communication with patients, detailed preoperative assessment of airways and perfect plan, appropriate endotracheal intubation approach and devices play important roles in awake tracheal intubation in difficult airway.

PGE2-EP3 signaling exacerbates hippocampus-dependent cognitive impairment after laparotomy by reducing expression levels of hippocampal synaptic plasticity-related proteins in aged mice.

AIM: Multifactors contribute to the development of postoperative cognitive dysfunction (POCD), of which the most important mechanism is neuroinflammation. Prostaglandin E2 (PGE2) is a key neuroinflammatory molecule and could modulate hippocampal synaptic transmission and plasticity. This study was designed to investigate whether PGE2 and its receptors signaling pathway were involved in the pathophysiology of POCD. METHODS: Sixteen-month old male C57BL/6J mice were exposed to laparotomy. Cognitive function was evaluated by fear conditioning test. The levels of PGE2 and its 4 distinct receptors (EP1-4) were assessed by biochemical analysis. Pharmacological or genetic methods were further applied to investigate the role of the specific PGE2 receptors. RESULTS: Here, we found that the transcription and translation level of the EP3 receptor in hippocampus increased remarkably, but not EP1, EP2, or EP4. Immunofluorescence results showed EP3 positive cells in the hippocampal CA1 region were mainly neurons. Furthermore, pharmacological blocking or genetic suppression of EP3 could alleviate surgery-induced hippocampus-dependent memory deficits and rescued the expression of plasticity-related proteins, including cAMP response element-binding protein (CREB), activity-regulated cytoskeletal-associated protein (Arc), and brain-derived neurotrophic factor (BDNF) in hippocampus. CONCLUSION: This study showed that PGE2-EP3 signaling pathway was involved in the progression of POCD and identified EP3 receptor as a promising treatment target.

One case with dexmedetomidine-induced stuporous state in epileptic patient undergoing abdominal surgery.

A 56-year-old epileptic patient underwent right hemicolectomy and cholecystectomy surgery under general endotracheal anesthesia. Anesthesia was maintained with sevoflurane, and sufentanil, rocuronium, and dexmedetomidine infusions. After the operation and confirmation of neuromuscular recovery, the patient woke from anesthesia within 15 min and successfully extubated. After the vital signs of patient were stable, the patient was transported to post anesthesia care unit (PACU). 6 h after the surgery, he fell into a stuporous state for lasting 14 h and EEG showed no epileptiform discharges. Stupor did re-occur in 2 days after operation. 36 hours after operation, all signs of the stuporous state resolved spontaneously. Apparent dexmedetomidine-induced stuporous state has not been reported in the human literature.

MHC-I promotes apoptosis of GABAergic interneurons in the spinal dorsal horn and contributes to cancer induced bone pain.

Cancer induced bone pain (CIBP) remains one of the most intractable clinical problems due to poor understanding of its underlying mechanisms. Recent studies demonstrate the decline of inhibitory interneurons, especially GABAergic interneurons in the spinal cord, can evoke generation of chronic pain. It has also been reported that neuronal MHC-I expression renders neurons vulnerable to cytotoxic CD8+ T cells and finally lead to neurons apoptosis in a variety neurological disorders. However, whether MHC-I could induce the apoptosis of GABAergic interneurons in spinal cord and contribute to the development of CIBP remains unknown. In this study, we investigated roles of MHC-I and underlying mechanisms in CIBP on a rat model. Our results showed that increased MHC-I expression on GABAergic interneurons could deplete GABAergic interneurons by inducing their apoptosis in the spinal dorsal horn of tumor-bearing rats. Pretreatment of MHC-I RNAi-lentivirus could prevent the apoptosis of GABAergic interneurons and therefore alleviated mechanical allodynia induced by tumor cells intratibial injection. Additionally, we also found that CD8+ T cells were colocalized with MHC-I and GABAergic neurons and presented a significant and persistent increase in the spinal cord of tumor-bearing rats. Taken together, these findings indicated that MHC-I could evoke CIBP by promoting apoptosis of GABAergic interneurons in the dorsal horn, and this apoptosis was closely related to local CD8+ T cells.

Recurrent cervicodorsal spinal intradural enterogenous cyst: case report and literature review.

This report described a recurrent enterogenous cyst of the cervicodorsal spinal canal occurred in an 8-year-old boy who experienced cervical back pain at the age of 5. He had been operated for mass lesion at the same level 3 years ago. The cervical and thoracic spine MRI showed a large intradural cyst at C7-T1. The cyst was subtotally removed via posterior approach using a laminectomy. Based on the results of immunostaining, it was identified as an enterogenous cyst. A literature review related to spinal cyst is also included.

Anesthetic management for craniotomy in a patient with massive cerebellar infarction and severe aortic stenosis: a case report.

Severe aortic stenosis combined with coronary heart disease remarkably increases the risk of perioperative morbidity and mortality during noncardiac surgery. Surgery and anesthesia often complicate the perioperative outcome if adequate monitoring and proper care are not taken. Therefore, understanding of the hemodynamic changes and anesthetic implications is an important for successful perioperative outcome. This report described the anesthetic management of a patient with a massive cerebellar infarction who was diagnosed with severe aortic stenosis combined with moderate aortic insufficiency and coronary heart disease and hypertension. He was prepared for aortic valve replacement and coronary bypass operation before massive cerebellar infarction occurred. And he received decompressive craniotomy and external ventricular drainage in the prone position under general anesthesia with endotracheal intubation.

Anaesthetic management of laparoscopic surgery for rectal cancer in patients of dilated cardiomyopathy with poor ejection fraction: a case report.

A patient with dilated cardiomyopathy with poor ejection fraction posted for laparoscopic surgery for rectal cancer which was successfully performed under general anesthesia with endotracheal intubation and mechanical ventilation was reported. Our observations strongly indicate that detailed preoperative assessment, watchful intraoperative monitoring, and skillful optimization of fluid status and hemodynamic play important role in the high risk patient under general anesthesia with endotracheal intubation and mechanical ventilation.

Monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles for imaging of epidermal growth factor receptor-targeted cells and gliomas.

The objective of this study was to successfully synthesize epidermal growth factor receptor monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles (EGFRmAb-SPIONs) and explore their biocompatibility and potential applications as a targeted magnetic resonance imaging (MRI) contrast agent for the EGFR-specific detection of brain glioma in vivo. After conjugation of EGFRmAb with SPIONs, the magnetic characteristics of EGFRmAb-SPIONs were investigated. Thereafter, the targeting abilities of EGFRmAb-SPIONs with MRI were qualitatively and quantitatively assessed in EGFR-positive C6 glioma cells in vitro and in a Wistar rat model bearing C6 glioma in vivo. Furthermore, the preliminary biocompatibility and toxicity of EGFRmAb-SPIONs were evaluated in normal rats through hematology assays and histopathologic analyses. Statistical analysis was performed using one-way analysis of variance and Student t-test, with a significance level of p < .05. From the results of EGFRmAb-SPION characterizations, the average particle size was 10.21 nm and the hydrodynamic diameter was 161.5 ± 2.12 nm. The saturation magnetization was 55 emu/g·Fe, and T2 relaxivity was 92.73 s-1mM-1 in distilled water. The preferential accumulation of the EGFRmAb-SPIONs within glioma and subsequent MRI contrast enhancement were demonstrated both in vitro in C6 cells and in vivo in rats bearing C6 glioma. After intravenous administration of EGFRmAb-SPIONs, T2-weighted MRI of the rat model with brain glioma exhibited an apparent hypointense region within glioma from 2 to 48 hours. The maximal image contrast was reached at 24 hours, where the signal intensity decreased and the R2 value increased by 30% compared to baseline. However, T2-weighted imaging of the rat model administered with SPIONs showed no visible signal changes within the tumor over the same time period. Moreover, no evident toxicities in vitro and in vivo with EGFRmAb-SPIONs were clearly identified based on the laboratory examinations. EGFRmAb-SPIONs could potentially be employed as a targeted contrast agent in the molecule-specific diagnosis of brain glioma in MRI.