GSDMD/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy.

BACKGROUND: Gasdermin D (GSDMD)-mediated pyroptotic cell death is implicated in the pathogenesis of cognitive deficits in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain largely unclear. Dynamin-related protein 1 (Drp1) facilitates mitochondrial fission and ensures quality control to maintain cellular homeostasis during infection. This study aimed to investigate the potential role of the GSDMD/Drp1 signaling pathway in cognitive impairments in a mouse model of SAE. METHODS: C57BL/6 male mice were subjected to cecal ligation and puncture (CLP) to establish an animal model of SAE. In the interventional study, mice were treated with the GSDMD inhibitor necrosulfonamide (NSA) or the Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1). Surviving mice underwent behavioral tests, and hippocampal tissues were harvested for histological analysis and biochemical assays at corresponding time points. Haematoxylin-eosin staining and TUNEL assays were used to evaluate neuronal damage. Golgi staining was used to detect synaptic dendritic spine density. Additionally, transmission electron microscopy was performed to assess mitochondrial and synaptic morphology in the hippocampus. Local field potential recordings were conducted to detect network oscillations in the hippocampus. RESULTS: CLP induced the activation of GSDMD, an upregulation of Drp1, leading to associated mitochondrial impairment, neuroinflammation, as well as neuronal and synaptic damage. Consequently, these effects resulted in a reduction in neural oscillations in the hippocampus and significant learning and memory deficits in the mice. Notably, treatment with NSA or Mdivi-1 effectively prevented these GSDMD-mediated abnormalities. CONCLUSIONS: Our data indicate that the GSDMD/Drp1 signaling pathway is involved in cognitive deficits in a mouse model of SAE. Inhibiting GSDMD or Drp1 emerges as a potential therapeutic strategy to alleviate the observed synaptic damages and network oscillations abnormalities in the hippocampus of SAE mice.

The effects of robot-assisted laparoscopic surgery with Trendelenburg position on short-term postoperative respiratory diaphragmatic function.

OBJECTIVE: To study how Pneumoperitoneum under Trendelenburg position for robot-assisted laparoscopic surgery impact the perioperative respiratory parameters, diagrammatic function, etc. METHODS: Patients undergoing robot-assisted laparoscopic surgery in the Trendelenburg position and patients undergoing general surgery in the supine position were selected. The subjects were divided into two groups according to the type of surgery: robot-assisted surgery group and general surgery group. ① Respiratory parameters such as lung compliance, oxygenation index, and airway pressure were recorded at 5 min after intubation, 1 and 2 h after pneumoperitoneum. ② Diaphragm excursion (DE) and diaphragm thickening fraction (DTF) were recorded before entering the operating room (T1), immediately after extubation (T2), 10 min after extubation (T3), and upon leaving the postanesthesia care unit (T4). ③ Peripheral venous blood (5 ml) was collected before surgery and 30 min after extubation and was analyzed by enzyme-linked immunosorbent assay to determine the serum concentration of Clara cell secretory protein 16 (CC16) and surfactant protein D (SP-D). RESULT: ① Compared with the general surgery group (N = 42), the robot-assisted surgery group (N = 46) presented a significantly higher airway pressure and lower lung compliance during the surgery(P < 0.001). ② In the robot-assisted surgery group, the DE significantly decreased after surgery (P < 0.001), which persisted until patients were discharged from the PACU (P < 0.001), whereas the DTF only showed a transient decrease postoperatively (P < 0.001) and returned to its preoperative levels at discharge (P = 0.115). In the general surgery group, the DE showed a transient decrease after surgery(P = 0.011) which recovered to the preoperative levels at discharge (P = 1). No significant difference in the DTF was observed among T1, T2, T3, and T4. ③ Both the general and robot-assisted surgery reduced the postoperative serum levels of SP-D (P < 0.05), while the robot-assisted surgery increased the postoperative levels of CC16 (P < 0.001). CONCLUSION: Robot-assisted laparoscopic surgery significantly impairs postoperative diaphragm function, which does not recover to preoperative levels at PACU discharge. Elevated levels of serum CC16 after surgery suggest potential lung injury. The adverse effects may be attributed to the prolonged Trendelenburg position and pneumoperitoneum during laparoscopic surgery.

Proinflammatory activation of microglia in the cerebellum hyperexcites Purkinje cells to trigger ataxia.

Specific medications to combat cerebellar ataxias, a group of debilitating movement disorders characterized by difficulty with walking, balance and coordination, are still lacking. Notably, cerebellar microglial activation appears to be a common feature in different types of ataxic patients and rodent models. However, direct evidence that cerebellar microglial activation in vivo is sufficient to induce ataxia is still lacking. Here, by employing chemogenetic approaches to manipulate cerebellar microglia selectively and directly, we found that specific chemogenetic activation of microglia in the cerebellar vermis directly leads to ataxia symptoms in wild-type mice and aggravated ataxic motor deficits in 3-acetylpyridine (3-AP) mice, a classic mouse model of cerebellar ataxia. Mechanistically, cerebellar microglial proinflammatory activation induced by either chemogenetic M3D(Gq) stimulation or 3-AP modeling hyperexcites Purkinje cells (PCs), which consequently triggers ataxia. Blockade of microglia-derived TNF-α, one of the most important proinflammatory cytokines, attenuates the hyperactivity of PCs driven by microglia. Moreover, chemogenetic inhibition of cerebellar microglial activation or suppression of cerebellar microglial activation by PLX3397 and minocycline reduces the production of proinflammatory cytokines, including TNF-α, to effectively restore the overactivation of PCs and alleviate motor deficits in 3-AP mice. These results suggest that cerebellar microglial activation may aggravate the neuroinflammatory response and subsequently induce dysfunction of PCs, which in turn triggers ataxic motor deficits. Our findings thus reveal a causal relationship between proinflammatory activation of cerebellar microglia and ataxic motor symptoms, which may offer novel evidence for therapeutic intervention for cerebellar ataxias by targeting microglia and microglia-derived inflammatory mediators.

Basolateral Amygdala Reactive Microglia May Contribute to Synaptic Impairment and Depressive-Like Behavior in Mice with Bone Cancer Pain.

Anxiety and depression induced by cancer-related pain disturb quality of life and willingness to survive. As a component of the limbic system, the basolateral amygdala (BLA) is critical for processing negative emotions. The reactive microglial engulfment of synapses may promote depression during adolescence. However, whether microglia phagocytose synapses to mediate cancer pain-induced depression remains unclear. The present study established a bone cancer-pain model to investigate the association between dendritic spine synapses and depressive-like behavior and explore the phagocytic function of microglia in the BLA. We found that tumor-bearing mice experienced postoperative pain-related depression, and their BLAs exhibited reactive microglia, as well as phagocytic synapses. The microglial inhibitor minocycline effectively mitigated depressive behavior, synaptic damage, and the phagocytic function of microglia. Our study implicates microglia-mediated synaptic loss in the BLA may act as the pathological basis of depressive-like behavior in bone cancer pain model.

[Research Progress of CD4+T Cells-mediated Regulation of Neuroinflammation Involved in Neurodegenerative Diseases].

Neurodegenerative diseases are associated with neuroinflammation,oxidative stress,and aging,which can lead to cognitive and motor dysfunctions.Recent studies suggest that the development of neurodegenerative diseases is related to adaptive immunity,in which CD4+T cells are involved as adaptive immune cells.Through different pathways,CD4+T cells differentiate into effector and regulatory subsets,which may have different effects on the progression of neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease,multiple sclerosis,and amyotrophic lateral sclerosis.Here,we review the role and research progress of CD4+T cells in neurodegenerative diseases.

Effect of neuromuscular blockade on transcranial electric motor evoked potentials during surgical correction for idiopathic scoliosis under total intravenous anesthesia.

Transcranial electric motor evoked potentials (TCeMEPs) play an important role in reducing the risk of iatrogenic paraplegia. TCeMEPs could be obviously suppressed by neuromuscular blockade (NMB). The aims of this study were to examine the effects of NMB on TCeMEPs and to determine an appropriate level of partial neuromuscular blockade (pNMB) for TCeMEPs during surgical correction of idiopathic scoliosis under total intravenous anesthesia (TIVA). All patients were maintained with TIVA. The pNMB levels were classified into five phases: one or two train-of-four (TOF) counts (TOF1); three TOF counts, or T4/T1 (TOFR, T1,4, first or four twitch height of TOF) ≤ 15% (TOF2); TOFR at 16-25% (TOF3); TOFR at 26-50% (TOF4); and TOFR at 51-75% (TOF5). No neuromuscular blockade (nNMB) was achieved when TOFR was more than 75%. The absolute and relative latency, amplitude and area under curve (AUC), efficacy of TCeMEPs and rate of unexpected movement were compared among these phases. Neither the amplitude and AUC nor the efficacy of TCeMEPs were affected at TOF4-5 of abductor halluces muscles TCeMEPs (AH-TCeMEPs) or at TOF3-5 of tibialis anterior muscles TCeMEPs (TA-TCeMEPs) compared with nNMB. However, the rate of unexpected movement was increased significantly at TOF5 and nNMB compared with TOF1 and TOF4. The application of pNMB with TOFR aimed at 26-50% for AH-TCeMEPs or 16-50% for TA-TCeMEPs seems to be an appropriate regimen for TCeMEPs during surgical correction for idiopathic scoliosis under TIVA.

Relationship between Annualized Case Volume and Mortality in Sepsis: A Dose-Response Meta-analysis.

BACKGROUND: The relationship between annualized case volume and mortality in patients with sepsis is not fully understood. The authors performed a dose-response meta-analysis to assess the effect of annualized case volume on mortality among patients with sepsis in the intensive care unit, emergency department, or hospital, hypothesizing that higher annualized case volume may lead to lower mortality. METHODS: The authors searched PubMed and Embase through July 2015 to identify observational studies that examined the relationship between annualized case volume and mortality in sepsis. The predefined outcome was mortality. Odds ratios with 95% CIs were pooled using a random-effects model. RESULTS: Ten studies involving 3,495,921 participants and 834,009 deaths were included. The pooled estimate suggested that annualized case volume was inversely associated with mortality (odds ratio, 0.76; 95% CI, 0.65 to 0.89; P = 0.001), with high heterogeneity (I = 96.6%). The relationship was consistent in most subgroup analyses and robust in sensitivity analysis. Dose-response analysis identified a nonlinear relationship between annualized case volume and mortality (P for nonlinearity less than 0.001). CONCLUSIONS: This meta-analysis confirmed the study hypothesis and provided strong evidence for an inverse and a nonlinear dose-response relationship between annualized case volume and mortality in patients with sepsis. Variations in cutoff values of category for annualized case volume across studies may mainly result in the overall heterogeneity. Future studies should uncover the mechanism of volume-mortality relationship and standardize the cutoff values of category for annualized case volume in patients with sepsis.

[Effects of ulinastatin on cognitive function in patients with coronary artery bypass grafting].

OBJECTIVE: To investigate the effects of ulinastatin(UTI) on postoperative cognitive function in patients undergoing coronary artery bypass grafting. METHODS: One hundred and twenty-seven patients undergoing elective coronary artery bypass surgery were randomly divided into three groups:high-dose UTI group(16000 U/kg i.v.), low-dose UTI group(8000 U/kg i.v.) and control group(normal saline). The levels of plasma cortisol were measured before and one day after surgery. The level of IL-6, IL-10, TNF-α and S100ß were measured before operation(T0), at open chest(T1), end of operation(T2), 6 h(T3)and 24 h(T4) after operation. A neuropsychological test scale was to evaluate the cognitive function 1 day before operation, 1 week and 3 months after operation. RESULTS: Ninety-three patients completed the study. There was no significant difference in general information of patients among three groups(P>0.05). The level of plasma cortisol one day after operation was significantly higher than that before operation in control group(P<0.01). The levels of plasma cortisol in high-dose UTI group and low-dose UTI group were lower than that of control group(P<0.01). In all groups, the level of plasma IL-6, IL-10, TNF-α and S100B increased remarkably at T2, T3, T4 compared to those at T0(all P<0.05). The level of plasma IL-6, TNF-α(at T2, T3, T4)and S100ß(at T3)in high-dose UTI group and low-dose UTI group were all lower than those of control group(P<0.05),while there were no significant differences between high-dose UTI group and low-dose UTI group(P>0.05). The incidence of postoperative cognitive dysfunction in POCD 1 week after operation in high-dose UTI and low-dose UTI groups(25.8% and 23.3%)was lower than that in control group(50.0%), while there were no significant difference 1 month after operation between high-dose UTI group(12.9%) or low-dose UTI group(16.7%)and control group(28.1%). The level of plasma S100ß at T2 of POCD patients(n=31)was higher than that of non-POCD group(n=62)(P<0.05). CONCLUSION: Ulinastatin can reduce the incidence of postoperative cognitive dusfunction 1 week after coronary artery bypass surgery, which might be associated with inhibition of inflammation and S100ß expression.

BeMADS1 is a key to delivery MADSs into nucleus in reproductive tissues-De novo characterization of Bambusa edulis transcriptome and study of MADS genes in bamboo floral development.

BACKGROUND: The bamboo Bambusa edulis has a long juvenile phase in situ, but can be induced to flower during in vitro tissue culture, providing a readily available source of material for studies on reproductive biology and flowering. In this report, in vitro-derived reproductive and vegetative materials of B. edulis were harvested and used to generate transcriptome databases by use of two sequencing platforms: Illumina and 454. Combination of the two datasets resulted in high transcriptome quality and increased length of the sequence reads. In plants, many MADS genes control flower development, and the ABCDE model has been developed to explain how the genes function together to create the different whorls within a flower. RESULTS: As a case study, published floral development-related OsMADS proteins from rice were used to search the B. edulis transcriptome datasets, identifying 16 B. edulis MADS (BeMADS). The BeMADS gene expression levels were determined qRT-PCR and in situ hybridization. Most BeMADS genes were highly expressed in flowers, with the exception of BeMADS34. The expression patterns of these genes were most similar to the rice homologs, except BeMADS18 and BeMADS34, and were highly similar to the floral development ABCDE model in rice. Transient expression of MADS-GFP proteins showed that only BeMADS1 entered leaf nucleus. BeMADS18, BeMADS4, and BeMADS1 were located in the lemma nucleus. When co-transformed with BeMADS1, BeMADS15, 16, 13, 21, 6, and 7 translocated to nucleus in lemmas, indicating that BeMADS1 is a key factor for subcellular localization of other BeMADS. CONCLUSION: Our study provides abundant B. edulis transcriptome data and offers comprehensive sequence resources. The results, molecular materials and overall strategy reported here can be used for future gene identification and for further reproductive studies in the economically important crop of bamboo.

Single nucleotide polymorphisms of ADH1B, ADH1C and ALDH2 genes and esophageal cancer: a population-based case-control study in China.

Alcohol drinking is a major risk factor for esophageal cancer (EC) and the metabolism of ethanol has been suggested to play an important role in esophageal carcinogenesis. Epidemiologic studies, including genomewide association studies (GWAS), have identified single nucleotide polymorphisms (SNPs) in alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs) to be associated with EC. Using a population-based case-control study with 858 EC cases and 1,081 controls conducted in Jiangsu Province, China, we aimed to provide further information on the association of ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms with EC in a Chinese population. Results showed that ADH1B (rs1229984) was associated with EC with odds ratios (ORs) of 1.34 [95% confidence interval (CI): 1.08-1.66] for G-allele carriers compared to A/A homozygotes. No heterogeneity was detected on this association across different strata of alcohol drinking and tobacco smoking. Statistical interaction between ALDH2 (rs671) and alcohol drinking on EC susceptibility in both additive and multiplicative scales was observed. Compared to G/G homozygotes, A-allele carriers were positively associated with EC among moderate/heavy drinkers (OR = 1.64, 95% CI: 1.12-2.40) and inversely associated with EC among never/light drinks (OR = 0.75, 95% CI: 0.54-1.03). In addition, statistical interaction between ALDH2 and ADH1B polymorphisms on EC susceptibility among never/light drinkers was indicated. We did not observe association of ADH1C polymorphism with EC. In conclusion, our findings indicated that ADH1B (rs1229984) was associated with EC independent of alcohol drinking and tobacco smoking status and alcohol drinking interacted with ALDH2 (rs671) on EC susceptibility in this high-risk Chinese population.

Mental health changes in elderly patients undergoing non-cardiac surgery during the COVID-19 pandemic in China.

BACKGROUND: The COVID-19 pandemic has a heavy impact on the mental health of elderly surgical patients worldwide. In particular, the elderly patients faced considerable psychological stress due to various environmental and medical factors during the outbreak. This study aims to examine changes in mental health trends among non-cardiac surgical patients aged 65 and above in China during the COVID-19 pandemic. METHODS: This multi-center, convenient sampling, longitudinal observational study was conducted from April 1, 2020 to April 30, 2022. Primary outcome was the prevalence of postoperative depression. Secondary outcome was the prevalence of postoperative anxiety. Follow-up was conducted separately at 7 days and 30 days after surgery. Depression symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9) scale. Anxiety symptoms were assessed using Generalized Anxiety Disorder-7 (GAD-7) scale, with scores of ≥5 defining positive depression or anxiety symptoms. Multivariate logistic regression analysis was used to investigate risk factors of mental health status in more elderly patients undergoing non-cardiac surgery. RESULTS: A total of 4639 patients were included, of whom 2279 (46.0 %) were male, 752 (15.2 %) were over the age of 75, and 4346 (93.7 %) were married. The monthly prevalence trends demonstrated that compared to the outbreak period, a significant reduction in the prevalence of depression and anxiety symptoms in elderly patients who underwent surgery during the post-pandemic period. In post-pandemic period, a statistically significant decrease in the prevalence of all severity depression and anxiety patients was noted at the 7-day follow-up, but no significant decrease was observed for severe depression and anxiety in the 30-day follow-up. In COVID-19 low-risk area, a significant overall decrease in prevalence of mental health was observed during the post-pandemic period compared to the outbreak period, including 7-day depression, 7-day anxiety, 30-day depression, and 30-day anxiety (all with P < 0.001). Female and patients with ≥2 comorbidities appeared to be more susceptible to postoperative depression and anxiety during the pandemic. LIMITATION: The absence of data from the early days of the COVID-19 outbreak. CONCLUSIONS: This study analyzed the prevalence of depression and anxiety in elderly non-cardiac patients during and after the COVID-19 pandemic, focusing on dimensions such as severity, risk-areas, gender, and comorbidity. Our findings revealed a significant decrease in the prevalence of depression and anxiety in elderly surgery patients during the post-pandemic period.

Intrathecal injection of metabotropic glutamate receptor subtype 3 and 5 agonist/antagonist attenuates bone cancer pain by inhibition of spinal astrocyte activation in a mouse model.

BACKGROUND: Astrocytes and metabotropic glutamate receptors play important roles in nociceptive processing. However, their roles in bone cancer pain were not well understood. This study sought to investigate whether selective mGluR3 and mGluR5 agonist or antagonist develop antinociceptive effects on bone cancer pain by inhibition of spinal astrocyte activation. METHODS: C3H/HeNCrlVr mice were inoculated into the intramedullary space of the femur with sarcoma NCTC 2472 cells to induce bone cancer pain. Quantitative real-time reverse transcription-polymerase chain reaction and Western blot experiments examined messenger RNA and protein expression of spinal glial fibrillary acidic protein, mGluR3, and mGluR5. The authors further investigated effects of intrathecal treatment with the mGluR3 agonist (APDC), the mGluR3 antagonist (LY341495), the mGluR5 agonist (CHPG), or the mGluR5 antagonist (MTEP) on nociceptive behaviors and spinal astrocyte activation associated with bone cancer pain. RESULTS: Inoculation of sarcoma cells, but not α-MEM solution, induced progressive bone cancer pain and resulted in up-regulation of glial fibrillary acidic protein, mGluR3, and mGluR5 expression on days 10, 14, and 21 postinoculation. Intrathecal administration of APDC and MTEP attenuated bone cancer-evoked spontaneous pain, mechanical allodynia, thermal hyperalgesia, and reduced spinal glial fibrillary acidic protein expression. However, treatment with LY341495 and CHPG induced thermal hyperalgesia and spinal glial fibrillary acidic protein expression in control mice. CONCLUSIONS: Spinal mGluR3 activation or mGluR5 inhibition reduced bone cancer pain. Inhibition of spinal astrocyte activation may contribute to the analgesic effects. These findings may lead to novel strategies for the treatment of bone cancer pain.

[Role of cannabinoid 2 receptor in the development of bone cancer pain].

OBJECTIVE: To explore the effects of cannabinoid 2 receptor (CB2) in the development of bone cancer pain in mice. METHODS: A total of 84 mice (C3H/HeJ) were randomly divided into 4 groups:tumor group (Group T, n = 30), medication administration group (Group J, n = 12), vehicle group (Group D, n = 12) and sham group (Group S, n = 30). And 2 × 10(5) osteolytic NCTC2472 cells in α-MEM were injected into medullary cavity of right distal femur to induce bone cancer pain in a murine model while sham mice received an injection of only α-MEM. All mice were tested for pain-related behaviors at pre-inoculation and at Days 5, 7, 10 and 14 post-inoculation. The tests included paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL). Group J and Group D were injected intrathecally with 2 µg JWH015 dissolved in 4% DMSO and only 4% DMSO respectively in a 5 µl. volume. Pain behavior tests were performed before and at 1, 6, 24, 48 and 72 h after an intrathecal injection. Lumbar intumescentia of mice in each group were harvested to examine the expression level of CB2 by Western blot after pain behavior tests at Days 5, 7, 10 and 14 post-inoculation and 12 h after an intrathecal injection. RESULTS: (1) Pain behavior tests:Mechanical allodynia appeared at Day 7 post-inoculation. The value of PWMT was (1.27 ± 0.28) g (P < 0.05) and it declined gradually to (0.53 ± 0.20) g at Day 14. The threshold of mechanical hyperalgesia increased to (1.00 ± 0.20) g at 6 h after an intrathecal injection of JWH015, peaked at (1.40 ± 0.39) g at 12 h, became alleviated after 48 h and recovered to the pre-dosing levels at 72 h. Thermal hyperalgesia appeared at Day 10 post-inoculation. The value of PWTL was (16.9 ± 0.4) s (P < 0.05) at Day 10 and declined to (11.5 ± 0.7) s at Day 14 post-inoculation. The threshold of thermal hyperalgesia increased to (15.7 ± 1.9) g at 6 h after an intrathecal injection of JWH015, peaked at (18.6 ± 2.3) g at 12 h, became alleviated after 48 h and recovered to the pre-dosing levels at 72 h. (2) Western blot: From Day 5 post-inoculation, the ratio of CB2/ß-actin increased gradually. Compared with the ratio of 0.190 ± 0.010 at Day 5 post-inoculation, the ratio of CB2/ß-actin increased to 0.660 ± 0.010 at Day 14 post-inoculation (P < 0.05); compared with the ratio of 0.903 ± 0.006 in group D at 12 h after an intrathecal injection of JWH015, the ratio of CB2/ß-actin 0.510 ± 0.010 significantly decreased (P < 0.05). CONCLUSION: The cannabinoid 2 receptor plays an important role in the formation of bone cancer pain.

Risk factors of postoperative nausea and vomiting following ambulatory surgery: A retrospective case-control study.

Objective: To explore potential risk factors of postoperative nausea and vomiting (PONV) following ambulatory surgery. Method: Clinical data of 1670 cases receiving ambulatory surgery in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from September 2017 to December 2019 were retrospectively analyzed. They were categorized to PONV group and non-PONV group, and perioperative data in both groups were analyzed for assessing risk factors of PONV following ambulatory laparoscopy. Results: There were 156/1,670 (9.3%) PONV cases, and the female and male incidence in recruited cases was 12.0% and 6.0%, respectively. Analyses on perioperative data of them identified that female gender [adjusted odds ratio (aOR) = 2.060, P < 0.001], operation time >1 h (aOR = 1.554, P = 0.011), postoperative pain at rest (aOR = 1.909, P = 0.013) and postoperative pain during activities (aOR = 3.512, P < 0.001) were independent risk factors of PONV following ambulatory surgery. Furthermore, postoperative pain at rest and during activities were linearly, positively correlated to the incidence of PONV. Conclusion: Female gender, operation time >1 h and postoperative pain are closely related with the incidence of PONV following ambulatory surgery. Alleviating postoperative pain properly is one of the methods to reduce risk factors of PONV following ambulatory surgery.

TREM2 and CD163 Ameliorate Microglia-Mediated Inflammatory Environment in the Aging Brain.

Aging decreases cognitive functions, especially learning and memory. Neuroinflammation is mediated by microglia and occurs in age-related neurodegenerative diseases. The expression profiles in a dataset of cognitively normal controls (GSE11882) were obtained from the Gene Expression Omnibus (GEO) database. Microarray data were used to explore the expression of age-related genes in the human hippocampus. A total of 120 differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was constructed. A total of 18 key genes were identified by the plugin cytoHubba in Cytoscape software. Two genes with a positive impact on cognition during aging were teased out: triggering receptor expressed on myeloid cells 2 (TREM2) and a scavenger receptor (CD163). Finally, the results of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) verified that the mRNA expression of these two genes was significantly upregulated in aged mice. Moreover, the levels of the inflammatory factors IL-1ß and IL-6 were significantly increased. TREM2 and CD163 may be upregulated to alleviate the inflammatory environment resulting from microglial activation in the aging brain, thereby delaying cognitive decline.

Does family history of cancer modify the effects of lifestyle risk factors on esophageal cancer? A population-based case-control study in China.

A population-based case-control study on esophageal cancer has been conducted since 2003 in Jiangsu Province, China. The aim of this analysis is to provide further evidence on the relationship between family history of cancer in first-degree relatives (FH-FDRs) and the risk of esophageal cancer, and to explore the joint effects for FH-FDR with major lifestyle risk factors. A total of 1,520 cases and 3,879 controls were recruited. Unconditional logistic regression was applied for evaluating independent association as well as potential interactions between FH-FDR and lifestyle risk factors on the risk of esophageal cancer. Population attributable fraction (PAF) was calculated to quantify the proportion of cases attributable to risk factors. Results showed that with a FH-FDR of any malignant tumor or esophageal cancer, there is a 1.64- and 2.22-fold risk of esophageal cancer, respectively. Association was increased when there was more than one affected FDR (OR = 3.14) and younger age at diagnosis of relatives. Exposure of both FH-FDR and lifestyle risk factors strongly associated with esophageal cancer. Significant superadditivity interaction was found for FH-FDR with fast eating speed and diets low in fruits and vegetables. The estimation of PAF indicated that the majority of cases were attributed to lifestyle risk factors. In conclusion, it was found that FH-FDR significantly increases the risk of esophageal cancer and could modify the effect of certain lifestyle risk factors. If comprehensive lifestyle interventions are carried out within high-risk populations, there is a high probability of curbing occurrences of esophageal cancer.

[Research on the features of DNA methylation in leaves of different chronological ages of Phyllostachys heterocycla var. pubescens based on the method of MSAP].

In order to probe the features of DNA methylation for bamboo stand with different chronological ages, the technique of methylation-sensitive amplified polymorphism (MSAP) was employed to detect DNA methylation in the paper. Experiment material is Moso bamboo (Phyllostachys heterocycla var. pubescens) leaves with 3 various chronological ages (5, 31, and > 60 years after seed germination). During the procedure of genome DNA extration and MSAP analysis, total 35 pairs of MSAP primers were amplyfied. The results showed that MSAP value for bamboo with those three chronological ages were respectively 24.44%, 28.21% and 32.12%, and full-methylation ratios were 16.57%, 19.41% and 21.23%. Meanwhile, the value of variable sites for methylation reached 52.3% and for demethylation was 10.3%. Therefore, it could be concluded that with ages increasing MSAP value rising for Moso bamboo. Moreover the result of variance analysis for methylation ratio indicated that no significant (P = 0.307 > 0.05) difference among individuals with the same ages, while significant (P < 0.001) difference exsited among different chronological ages. Throuygh ANOVA it showed that 6 pairs (E3/HM2, E3/HM6, E3/HM7, E4/HM5, E4/HM6 and E5/HM5) of primers had obvious influence on DNA methylation for ones with different chronological ages and could be used for further research.

Identification of hub genes associated with cognition in the hippocampus of Alzheimer's Disease.

Alzheimer's Disease (AD) is a neurodegenerative disease featured by cognitive impairment. This bioinformatic analysis was used to identify hub genes related to cognitive dysfunction in AD. The gene expression profile GSE48350 in the hippocampus of AD patients aged >70 years was obtained from the Gene Expression Omnibus (GEO) database. A total of 96 differentially expressed genes (DEGs) were identified, and subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses; a protein-protein interaction (PPI) network was constructed. The DEGs were enriched in synapse-related changes. A protein cluster was teased out of PPI. Furthermore, the cognition ranked the first among all the terms of biological process (BP). Next, 4 of 10 hub genes enriched in cognition were identified. The function of these genes was validated using APP/PS1 mice. Cognitive performance was validated by Morris Water Maze (MWM), and gene expression by RT-qPCR, Cholecystokinin (CCK), Tachykinin precursor 1 (TAC1), Calbindin 1 (CALB1) were downregulated in the hippocampus. These genes can provide new directions in the research of the molecular mechanism of AD.

Dorsal root ganglia NR2B-mediated Epac1-Piezo2 signaling pathway contributes to mechanical allodynia of bone cancer pain.

Mechanical allodynia is a painful perception of mechanical stimuli and one of the typical symptoms in bone cancer pain (BCP). Previous studies have revealed that mice and humans lacking mechanically activated Piezo2 channels do not sense mechanical stimuli. However, the underlying mechanism of Piezo2 in BCP has not been well established. The aim of the present study was to investigate whether exchange protein directly activated by cAMP 1 (Epac1) mediated Piezo2 signaling pathway may be responsible for the mechanical allodynia of BCP and whether N-methyl-D-aspartic acid (NMDA) receptor subunit 2B (NR2B) is involved in the pathway. In the present study, a BCP model was established in C3H/HeJ mice by intramedullary injection of osteosarcoma cells. The results of the mechanical allodynia test demonstrated a markedly decreased paw withdrawal mechanical threshold in BCP mice, accompanied by a significant increase in Epac1, NR2B proteins and Piezo2 mRNA expression levels in the ipsilateral dorsal root ganglion (DRG). Compared with the sham group, intrathecal Epac1 antisense oligodeoxynucleotides (Epac1-ASODN) effectively ameliorated the mechanical allodynia and decreased the expression levels of NR2B and Piezo2 in the tumor group. Pretreatment of naïve mice with a NR2B antagonist prevented the aggravation of mechanical allodynia and DRG Piezo2 levels induced by an Epac1 agonist. However, the NR2B agonist-induced increase in Piezo2 expression levels was not reversed by pretreatment with Epac1-ASODN. In conclusion, the results of the present study demonstrated that NR2B, which is a crucial downstream regulator of Epac1, may mediate the Epac1-Piezo2 pathway contributing to the development of the mechanical allodynia of BCP. The present study may enrich the theoretical knowledge of the mechanical allodynia of BCP and provide a potential analgesic strategy for clinical treatment.