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.

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.

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.

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.

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.

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.

[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.

Index-based dietary patterns and stomach cancer in a Chinese population.

OBJECTIVES: Dietary factors are of importance in the development of stomach cancer. This study aims to examine index-based dietary patterns associated with stomach cancer in a Chinese population. METHODS: Using data from a population-based case-control study conducted in Jiangsu Province, China, we included a total of 8432 participants (1900 stomach cancer cases and 6532 controls). Dietary data collected by food frequency questionnaire was evaluated by modified Chinese Healthy Eating Index-2016 (mCHEI-2016) and the US Healthy Eating Index-2015 (HEI-2015). Multiple logistic regression analyses were applied to examine the association of mCHEI-2016 and HEI-2015 with stomach cancer while adjusting for potential confounders. The possible interactions between mCHEI-2016 or HEI-2015 and established risk factors were explored. RESULTS: Among nonproxy interviews, after adjusting for potential confounding factors, a higher score of sodium, reflecting lower intake per day, was inversely associated with stomach cancer [odds ratio (OR), 0.95; 95% CI, 0.91-0.99 for mCHEI-2016; OR, 0.97; 95% CI, 0.94-0.99 for HEI-2015]. No clear associations with stomach cancer were identified for total scores of HEI-2015 (OR, 0.98; 95% CI, 0.87-1.10 with a 10-point increase, P trend = 0.98) and mCHEI-2016 (OR, 1.05; 95% CI, 0.94-1.17 with a 10-point increase, P trend = 0.22). However, the relation between stomach cancer and the mCHEI-2016 was modified by BMI, with a possible inverse association in normal-weight subjects. CONCLUSIONS: Our findings highlight that reduced intake of dietary sodium would prevent the development of stomach cancer. The data indicate a heterogeneity between normal weight and overweight's dietary factors in relation to stomach cancer.

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.

Sevoflurane plays a reduced role in cognitive impairment compared with isoflurane: limited effect on fear memory retention.

Isoflurane and sevoflurane are both inhalation anesthetics, but in clinical application, sevoflurane has been considered to be less suitable for long-term anesthesia because of its catabolic compounds and potential nephrotoxicity. Nevertheless, recent studies have shown that these two inhalation anesthetics are similar in hepatorenal toxicity, cost, and long-term anesthetic effect. Moreover, sevoflurane possibly has less cognitive impact on young mice. In this study, C57BL/6 mice aged 8-10 weeks were exposed to 1.2% isoflurane or 2.4% sevoflurane for 6 hours. Cognitive function and memory were examined in young mice using the novel object recognition, contextual fear conditioning, and cued-fear extinction tests. Western blot assay was performed to detect expression levels of D1 dopamine receptor, catechol-O-methyltransferase, phospho-glycogen synthase kinase-3ß, and total glycogen synthase kinase-3ß in the hippocampus. Our results show that impaired performance was not detected in mice exposed to sevoflurane during the novel object recognition test. Contextual memory impairment in the fear conditioning test was shorter in the sevoflurane group than the isoflurane group. Long-term sevoflurane exposure did not affect memory consolidation, while isoflurane led to memory consolidation and reduced retention. Downregulation of hippocampal D1 dopamine receptors and phosphorylated glycogen synthase kinase-3ß/total glycogen synthase kinase-3ß and upregulation of catechol-O-methyltransferase may be associated with differing memory performance after exposure to isoflurane or sevoflurane. These results confirm that sevoflurane has less effect on cognitive impairment than isoflurane, which may be related to expression of D1 dopamine receptors and catechol-O-methyltransferase and phosphorylation of glycogen synthase kinase-3ß in the hippocampus. This study was approved by the Institutional Animal Care and Use Committee, Nanjing University, China on November 20, 2017 (approval No. 20171102).

GLYX-13 pretreatment ameliorates long-term isoflurane exposure-induced cognitive impairment in mice.

Accumulating evidence indicates that inhalation anesthetics induce or increase the risk of cognitive impairment. GLYX-13 (rapastinel) acts on the glycine site of N-methyl-D-aspartate receptors (NMDARs) and has been shown to enhance hippocampus-dependent learning and memory function. However, the mechanisms by which GLYX-13 affects learning and memory function are still unclear. In this study, we investigated these mechanisms in a mouse model of long-term anesthesia exposure. Mice were intravenously administered 1 mg/kg GLYX-13 at 2 hours before isoflurane exposure (1.5% for 6 hours). Cognitive function was assessed using the contextual fear conditioning test and the novel object recognition test. The mRNA expression and phosphorylated protein levels of NMDAR pathway components, N-methyl-D-aspartate receptor subunit 2B(NR2B)-Ca2+/calmodulin dependent protein kinase II (CaMKII)-cyclic adenosine monophosphate response element binding protein (CREB), in the hippocampus were evaluated by quantitative RT-PCR and western blot assay. Pretreatment with GLYX-13 ameliorated isoflurane exposure-induced cognitive impairment and restored NR2B, CaMKII and CREB mRNA and phosphorylated protein levels. Intracerebroventricular injection of KN93, a selective CaMKII inhibitor, significantly diminished the effect of GLYX-13 on cognitive function and NR2B, CaMKII and CREB levels in the hippocampus. Taken together, our findings suggest that GLYX-13 pretreatment alleviates isoflurane-induced cognitive dysfunction by protecting against perturbation of the NR2B/CaMKII/CREB signaling pathway in the hippocampus. Therefore, GLYX-13 may have therapeutic potential for the treatment of anesthesia-induced cognitive dysfunction. This study was approved by the Experimental Animal Ethics Committee of Drum Tower Hospital affiliated to the Medical College of Nanjing University, China (approval No. 20171102) on November 20, 2017.

Photoacoustic treatment mitigates cognitive dysfunction in a model of sleep-wake rhythm disturbance.

Sleep-wake rhythm disturbances, which are characterized by abnormal sleep timing or duration, are associated with cognitive dysfunction. Photoacoustic treatments including light and sound stimulation have been found to be effective in modulating sleep patterns and improving cognitive behavior in abnormal sleep-wake pattern experiments. In this study, we examined whether light and sound interventions could reduce sleep-wake pattern disturbances and memory deficits in a sleep rhythm disturbance model. We established a model of sleep rhythm disturbance in C57BL/6J mice via a sleep deprivation method involving manual cage tapping, cage jostling, and nest disturbance. We used a Mini Mitter radio transmitter device to monitor motor activity in the mice and fear conditioning tests to assess cognitive function. Our results indicated that an intervention in which the mice were exposed to blue light (40-Hz flickering frequency) for 1 hour during their subjective daytime significantly improved the 24-hour-acrophase shift and reduced the degree of memory deficit induced by sleep deprivation. However, interventions in which the mice were exposed to a 40-Hz blue light at offset time or subjective night time points, as well as 2 Hz-blue light at 3 intervention time points (subjective day time, subjective night time, and offset time points), had no positive effects on circadian rhythm shift or memory deficits. Additionally, a 2000-Hz sound intervention during subjective day time attenuated the 24-hour-acrophase shift and memory decline, while 440-Hz and 4000-Hz sounds had no effect on circadian rhythms. Overall, these results demonstrate that photoacoustic treatment effectively corrected abnormal sleep-wake patterns and cognitive dysfunction associated with sleep-deprivation-induced disturbances in sleep-wake rhythm. All animal experiments were approved by the Experimental Animal Ethics Committee of Drum Tower Hospital Affiliated to the Medical College of Nanjing University, China (approval No. 20171102) on November 20, 2017.

Dietary Intake of Fatty Acids, Total Cholesterol, and Stomach Cancer in a Chinese Population.

To investigate the associations between dietary fatty acids and cholesterol consumption and stomach cancer (SC), we analyzed data from a population-based case-control study with a total of 1900 SC cases and 6532 controls. Dietary data and other risk or protective factors were collected by face-to-face interviews in Jiangsu Province, China, from 2003 to 2010. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple unconditional logistic regression models and an energy-adjusted method. The joint associations between dietary factors and known risk factors on SC were examined. We observed positive associations between dietary saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and total cholesterol and the development of SC, comparing the highest versus lowest quarters. Increased intakes of dietary SFAs (p-trend = 0.005; aOR, 1.11; 95% CI, 1.01-1.22 with a 7 g/day increase as a continuous variable) and total cholesterol (p-trend < 0.001; aOR, 1.13; 95% CI, 1.06-1.22 with a 250 mg/day increase as a continuous variable) were monotonically associated with elevated odds of developing SC. Our results indicate that dietary SFAs, MUFAs, and total cholesterol are associated with stomach cancer, which might provide a potential dietary intervention for stomach cancer prevention.

Consumption of garlic and its interactions with tobacco smoking and alcohol drinking on esophageal cancer in a Chinese population.

Garlic consumption has been associated inversely with esophageal cancer (EC); however, its interactions with tobacco smoking and alcohol consumption have never been evaluated in an epidemiological study. We evaluated the potential interactions between garlic intake and tobacco smoking as well as alcohol consumption in a population-based case-control study with 2969 incident EC cases and 8019 healthy controls. Epidemiologic data were collected by face-to-face interviews using a questionnaire. The adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated and additive and multiplicative interactions were evaluated using unconditional logistic regression models, adjusting for potential confounding factors. Semi-Bayes (SB) adjustments were used to reduce potential false-positive findings. EC was associated inversely with raw garlic intake [SB-adjusted OR for more than once a week=0.68, 95% CI: 0.57-0.80], with a strong dose-response pattern in the overall analysis and in the stratified analyses by smoking and drinking. EC was associated positively with smoking and alcohol drinking, with SB-adjusted OR of 1.73 (95% CI: 1.62-1.85) and 1.37 (95% CI: 1.28-1.46) in dose-response effects of increased intensity and longer duration of smoking/drinking. Moreover, garlic intake interacts with smoking [synergy index (S)=0.83, 95% CI: 0.67-1.02; ratio of OR=0.88, 95% CI: 0.80-0.98] and alcohol drinking (S=0.73, 95% CI: 0.57-0.93; ratio of OR=0.86, 95% CI: 0.77-0.95) both multiplicatively and additively. Our findings suggested that high intake of raw garlic may reduce EC risk and may interact with tobacco smoking and alcohol consumption, which might shed a light on the development of EC as well as a potential dietary intervention among high-risk smokers and drinkers for EC prevention in the Chinese population.

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.

Restrictive Versus Liberal Strategy for Red Blood-Cell Transfusion: A Systematic Review and Meta-Analysis in Orthopaedic Patients.

BACKGROUND: Current guidelines recommend restrictive criteria for red blood-cell transfusion in most clinical settings. However, patients undergoing orthopaedic surgery may require distinct transfusion criteria since benefits and potential harm often vary considerably based on patient characteristics and surgical procedures. We aimed to assess the efficacy and safety of restrictive transfusion in patients undergoing orthopaedic surgery, especially in important subgroups. METHODS: Electronic databases were searched to identify randomized controlled trials investigating restrictive (mostly a hemoglobin level of 8.0 g/dL or symptomatic anemia) versus liberal (mostly a hemoglobin level of 10.0 g/dL) transfusion in patients undergoing orthopaedic surgery. For the primary outcome of cardiovascular events, we performed random-effects meta-analyses to synthesize the evidence and to assess the effects in different subgroups according to patient characteristics (with versus without preexisting cardiovascular disease) and surgical procedures (hip fracture surgery versus elective arthroplasty). RESULTS: Ten trials involving 3,968 participants who underwent hip or knee surgery were included. Mean participant age ranged from 68.7 to 86.9 years. Compared with liberal transfusion, restrictive transfusion increased the risk of cardiovascular events (8 trials; 3,618 participants; relative risk [RR], 1.51; 95% confidence interval [CI], 1.16 to 1.98; p = 0.003; with no heterogeneity across all trials), irrespective of preexisting cardiovascular disease (pinteraction = 0.63). In a subgroup analysis, the increase was observed in patients undergoing hip fracture surgery (RR, 1.51; 95% CI, 1.08 to 2.10; p = 0.02), but did not reach significance in those undergoing elective arthroplasty (RR, 1.53; 95% CI, 0.96 to 2.44; p = 0.07). To minimize the bias caused by variations in transfusion threshold, we conducted an analysis that only included trials using 8.0 g/dL hemoglobin or symptomatic anemia as the threshold for restrictive transfusion and obtained identical results (6 trials; 2,872 participants; RR, 1.51; 95% CI, 1.09 to 2.08; p = 0.01; I = 0%). The 2 arms did not differ with respect to the rates of all infections, 30-day mortality, thromboembolic events, wound infection, pulmonary infection (mainly pneumonia), and cerebrovascular accidents (mainly stroke). CONCLUSIONS: In patients undergoing orthopaedic surgery, when compared with liberal transfusion, restrictive transfusion increases the risk of cardiovascular events irrespective of preexisting cardiovascular disease. Importantly, the increased risk was observed in patients undergoing hip fracture surgery but did not reach significance in those undergoing elective arthroplasty. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Association between intraoperative hypotension and 30-day mortality, major adverse cardiac events, and acute kidney injury after non-cardiac surgery: A meta-analysis of cohort studies.

BACKGROUND: The association between intraoperative hypotension (IOH) and postoperative outcomes is not fully understood. We performed a meta-analysis to determine whether IOH is associated with increased risk of 30-day mortality, major adverse cardiac events (MACEs) and acute kidney injury (AKI) after non-cardiac surgery. METHODS: We searched PubMed and Embase through May 2016 to identify cohort studies that investigated the association between IOH and risk of 30-day mortality, MACEs, or AKI in adult patients after non-cardiac surgery. Ascertainment of IOH and assessment of outcomes were defined by the individual study. Considering the level of clinical heterogeneity, adjusted odds ratios (ORs) with 95% confidence interval (CIs) were pooled using a random-effects model. This meta-analysis is registered on PROSPERO (CRD42016049405). RESULTS: We included 14 cohort studies that were heterogeneous in terms of definition of IOH. IOH alone was associated with increased risk of 30-day mortality (OR 1.29 [95% CI, 1.19-1.41]), MACEs (OR 1.59 [95% CI, 1.23-2.05]), especially myocardial injury (OR 1.67 [95% CI, 1.31-2.13]), and AKI (OR 1.39 [95% CI, 1.09-1.77]). Triple low (IOH coincident with low bispectral index and low minimum alveolar concentration) also predicts increased risk of 30-day mortality (OR 1.32 [95% CI, 1.03-1.68]). CONCLUSIONS: IOH alone significantly increases the risk of postoperative 30-day mortality, MACEs, especially myocardial injury, and AKI in adult patients after non-cardiac surgery. Triple low also predicts increased risk of 30-day mortality after non-cardiac surgery. These findings provide evidence that IOH should be recognized as an independent risk factor for postoperative adverse outcomes after non-cardiac surgery.