Pathological and immunohistochemical analysis of gastric mucosa after one anastomosis gastric bypass surgery.

BACKGROUND: One anastomosis gastric bypass (OAGB) is now the third most common bariatric surgery worldwide. This procedure is garnering increasing attention, but its complication of bile reflux and the associated risk of gastric carcinogenesis remains controversial. OBJECTIVE: The study aims to assess the impact of bile reflux on the gastric mucosa by comparing pathological and immunohistochemical results of gastric mucosa before and 2 years after OAGB surgery. METHODS: This retrospective study analyzed gastric lesions observed in gastroscopy before and after OAGB surgery. Pathological examinations were conducted on mucosal samples from proximal, middle and distal part of stomach, with a particular focus on the expression of Ki-67, P53, and CDX2 in immunohistochemistry. Ki-67 indicates cellular proliferation, P53 is a tumor suppressor protein, and CDX2 is a marker for intestinal differentiation. RESULTS: A total of 16 patients completed the follow-up. Regarding gastritis, presurgery nonerosive gastritis was found in two cases (12.5%), and postsurgery in six cases (37.5%). Erosive gastritis increased from one case (6.2%) presurgery to three cases (18.7%) postsurgery, totaling an increase from three to nine cases (p = .028). Bile reflux in the stomach increased from one case (6.2%) presurgery to three cases (18.7%) postsurgery. Most lesions in the proximal, middle, and distal part of stomach were relatively mild, with normal tissue states being predominant. Mild inflammation was found in all three areas, whereas moderate inflammation, intestinal metaplasia, and glandular atrophy were less common. No cases of severe inflammation were noted. The expression of gastric biomarkers CDX-2, Ki67, and P53 showed no significant statistical variation in different areas. CONCLUSION: Bile reflux does occur after OAGB, but its incidence is not high. Based on the immunohistochemical and pathological results of the gastric mucosa 2 years post-OAGB, there seems to be no significant causal relationship between OAGB and oncogenic inflammation around the gastric tube.

Increased TMEM166 Level in Patients with Postoperative Stroke after Carotid Endarterectomy.

Postoperative stroke is a challenging and potentially devastating complication after elective carotid endarterectomy (CEA). We previously demonstrated that transmembrane protein 166 (TMEM166) levels were directly related to neuronal damage after cerebral ischemia-reperfusion injury in rats. In this subsequent clinical study, we aimed to evaluate the prognostic value of TMEM166 in patients suffering from post-CEA strokes. Thirty-five patients undergoing uncomplicated elective CEA and 8 patients who suffered ischemic strokes after CEA were recruited. We evaluated the protein level and expression of TMEM166 in patients diagnosed with postoperative strokes and compared it to those in patients who underwent uncomplicated elective CEA. Blood samples and carotid artery plaques were collected and analyzed. High expressions of TMEM166 were detected by immunofluorescence staining and Western Blot in carotid artery plaques of all patients who underwent CEA. Furthermore, circulating TMEM166 concentrations were statistically higher in post-CEA stroke patients than in patients allocated to the control group. Mean plasma concentrations of inflammatory markers, including interleukin 6 (IL-6) and C-reactive protein (CRP), were also elevated in patients with postoperative strokes. Therefore, based on these findings, we hypothesize that elevated TMEM166 levels, accompanied by a strong inflammatory response, serve as a useful biomarker for risk assessment of postoperative stroke following CEA.

A53T α-synuclein mutation increases susceptibility to postoperative delayed neurocognitive recovery via hippocampal Ang-(1-7)/MasR axis.

Delayed neurocognitive recovery (dNCR) is a common complication in geriatric surgical patients. The impact of anesthesia and surgery on patients with neurodegenerative diseases, such as Parkinson's disease (PD) or prion disease, has not yet been reported. In this study, we aimed to determine the association between a pre-existing A53T genetic background, which involves a PD-related point mutation, and the development of postoperative dNCR. We observed that partial hepatectomy induced hippocampus-dependent cognitive deficits in 5-month-old A53T transgenic mice, a model of early-stage PD without cognitive deficits, unlike in age-matched wild-type (WT) mice. We respectively examined molecular changes at 6 h, 1 day, and 2 days after partial hepatectomy and observed that cognitive changes were accompanied by weakened angiotensin-(1-7)/Mas receptor [Ang-(1-7)/MasR] axis, increased alpha-synuclein (α-syn) expression and phosphorylation, decreased methylated protein phosphatase-2A (Me-PP2A), and prompted microglia M1 polarization and neuronal apoptosis in the hippocampus at 1 day after surgery. Nevertheless, no changes in blood-brain barrier (BBB) integrity or plasma α-syn levels in either A53T or WT mice. Furthermore, intranasal administration of selective MasR agonist AVE 0991, reversed the mentioned cognitive deficits in A53T mice, enhanced MasR expression, reduced α-syn accumulation and phosphorylation, and attenuated microglia activation and apoptotic response. Our findings suggest that individuals with the A53T genetic background may be more susceptible to developing postoperative dNCR. This susceptibility could be linked to central α-syn accumulation mediated by the weakened Ang-(1-7)/MasR/methyl-PP2A signaling pathway in the hippocampus following surgery, independent of plasma α-syn level and BBB.

Association between pediatric postoperative delirium and regional cerebral oxygen saturation: a prospective observational study.

BACKGROUND: Postoperative delirium (POD) represents a prevalent and noteworthy complication in the context of pediatric surgical interventions. In recent times, a hypothesis has emerged positing that cerebral ischemia and regional cerebral oxygen desaturation might serve as potential catalysts in the pathogenesis of POD. The primary aim of this study was to methodically examine the potential relationship between POD and regional cerebral oxygen saturation (rSO2) and to assess the predictive and evaluative utility of rSO2 in the context of POD. METHODS: This prospective observational study was conducted at the Children's Hospital, Zhejiang University School of Medicine, Zhejiang, China, spanning the period from November 2020 to March 2021. The research cohort comprised children undergoing surgical procedures within this clinical setting. To measure rSO2 dynamics, cerebral near-infrared spectroscopy (NIRS) was used to monitor rSO2 levels both before and after surgery. In addition, POD was assessed in the paediatric patients according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria. The analysis of the association between the rSO2 index and the incidence of POD was carried out through the application of either the independent samples t-test or the nonparametric rank-sum test. To ascertain the threshold value of the adjusted rSO2 index for predictive and evaluative purposes regarding POD in the pediatric population, the Receiver Operating Characteristics (ROC) curve was employed. RESULTS: A total of 211 cases were included in this study, of which 61 (28.9%) developed POD. Participants suffering delirium had lower preoperative rSO2mean, lower preoperative rSO2min, and lower postoperative rSO2min, higher ∆rSO2mean, higher amount of ∆rSO2mean, lower ∆rSO2min (P < 0.05). Preoperative rSO2mean (AUC = 0.716, 95%CI 0.642-0.790), ∆rSO2mean (AUC = 0.694, 95%CI 0.614-0.774), amount of ∆rSO2mean (AUC = 0.649, 95%CI 0.564-0.734), preoperative rSO2min (AUC = 0.702, 96%CI 0.628-0.777), postoperative rSO2min (AUC = 0.717, 95%CI 0.647-0.787), and ∆rSO2min (AUC = 0.714, 95%CI 0.638-0.790) performed well in sensitivity and specificity, and the best threshold were 62.05%, 1.27%, 2.41%, 55.68%, 57.36%, 1.29%. CONCLUSIONS: There is a close relationship between pediatric POD and rSO2. rSO2 could be used as an effective predictor of pediatric POD. It might be helpful to measure rSO2 with NIRS for early recognizing POD and making it possible for early intervention.

Hypometabolism in the Posteromedial Temporal and Medial Occipital Cortex on Preoperative 2-Deoxy-2-(18F) Fluoro-D-Glucose Positron Emission Tomography Suggests Exacerbation of Visual Field Defects After Surgery for Temporal Lobe Epilepsy: A Retrospective Long-Term Follow-Up Study.

OBJECTIVE: Surgery is a good treatment option for drug-resistant temporal lobe epilepsy (TLE). 2-deoxy-2-(18F) fluoro-D-glucose (FDG) positron emission tomography (PET) is used to detect epileptic foci as hypometabolic lesions in presurgical evaluation. Visual field defects (VFDs) in the contralateral homonymous upper quadrant are common postoperative complications in TLE. This study aimed to quantify VFDs using pattern deviation probability plots (PDPPs) and examine the effect of hypometabolism in FDG-PET on VFDs. METHODS: This study included 40 patients. Both visual fields were assessed using the Humphrey field analyzer preoperatively and 3 months and 2 years postoperatively. PDPPs with <0.5% confidence level counted in the contralateral homonymous upper quadrant. FDG-PET results were compared between groups with (15 patients) and without (24 patients) hypometabolism in the optic radiation. RESULTS: All 40 patients were evaluated by Humphrey field analyzer at 3 months postoperatively and 39 at 2 years postoperatively. The incidence of VFDs 3 months postoperatively was 35/40 (87.5%), and 17/40 (42.5%) patients had severe VFDs. In cases of surgery on the left temporal lobe, ipsilateral eyes appeared to be more significantly affected than contralateral eyes. VFDs were more severe in patients with FDG hypometabolism than in those without hypometabolism in posteromedial temporal and medial occipital cortex (P < 0.01); however, 85% of patients with FDG hypometabolism had a reduced VFD 2 years postoperatively. CONCLUSIONS: PDPP counting is useful for quantifying VFDs. Preoperative dysfunction indicated by preoperative FDG-PET in the posteromedial temporal and medial occipital cortex could enhance VFDs early after TLE surgery.

Salivary metabolites as potential predictive biomarkers for lung surgery complications: a retrospective cross-sectional study.

PURPOSE: Saliva is often used as a tool for identifying systemic diseases because of the noninvasive nature of its collection. Moreover, salivary metabolites can be potential predictive factors for postoperative survival. We conducted the present study to establish whether salivary metabolites can function as predictive biomarkers for lung surgery complications. METHODS: Unstimulated salivary samples were collected from 412 patients before lung surgery. Salivary metabolites were analyzed comprehensively by capillary electrophoresis mass spectrometry. Clinical data with the discriminatory ability of biomarkers were assessed to predict lung surgery complications using multivariate logistic regression analysis. The primary endpoint was the risk factors for postoperative complications of Clavien-Dindo grade ≥ III. RESULTS: Postoperative complications of Clavien-Dindo grade ≥ III developed in 36 patients (8.7%). There was no postoperative 30-day mortality. Male sex (odds ratio [OR], 3.852; 95% confidence interval CI 1.455-10.199; p = 0.007) and salivary gamma-butyrobetaine (OR, 0.809; 95% CI 0.694-0.943; p = 0.007) were identified as significant risk factors for postoperative complications of Clavien-Dindo grade ≥ III. CONCLUSION: Salivary metabolites are potential noninvasive biomarkers for predicting postoperative complications of lung surgery.

Temporal and Spatial Patterns of Inflammation and Tissue Injury in Patients with Postoperative Respiratory Failure after Lung Resection Surgery: A Nested Case-Control Study.

Thoracic surgeries involving resection of lung tissue pose a risk of severe postoperative pulmonary complications, including acute respiratory distress syndrome (ARDS) and respiratory failure. Lung resections require one-lung ventilation (OLV) and, thus, are at higher risk of ventilator-induced lung injury (VILI) attributable to barotrauma and volutrauma in the one ventilated lung, as well as hypoxemia and reperfusion injury on the operated lung. Further, we also aimed to assess the differences in localized and systemic markers of tissue injury/inflammation in those who developed respiratory failure after lung surgery versus matched controls who did not develop respiratory failure. We aimed to assess the different inflammatory/injury marker patterns induced in the operated and ventilated lung and how this compared to the systemic circulating inflammatory/injury marker pattern. A case-control study nested within a prospective cohort study was performed. Patients with postoperative respiratory failure after lung surgery (n = 5) were matched with control patients (n = 6) who did not develop postoperative respiratory failure. Biospecimens (arterial plasma, bronchoalveolar lavage separately from ventilated and operated lungs) were obtained from patients undergoing lung surgery at two timepoints: (1) just prior to initiation of OLV and (2) after lung resection was completed and OLV stopped. Multiplex electrochemiluminescent immunoassays were performed for these biospecimen. We quantified 50 protein biomarkers of inflammation and tissue injury and identified significant differences between those who did and did not develop postoperative respiratory failure. The three biospecimen types also display unique biomarker patterns.

Relationship between postoperative biomarkers of neuronal injury and postoperative cognitive dysfunction: A meta-analysis.

Early biomarkers are needed to identify patients at risk of developing postoperative cognitive dysfunction (POCD). Our objective was to determine neuronal injury-related biomarkers with predictive values for this condition. Six biomarkers (S100ß, neuron-specific enolase [NSE], amyloid beta [Aß], tau, neurofilament light chain, and glial fibrillary acidic protein) were evaluated. According to the first postoperative sampling time, observational studies showed that S100ß was significantly higher in patients with POCD than in those without POCD (standardized mean difference [SMD]: 6.92, 95% confidence interval [CI]: 4.44-9.41). The randomized controlled trial (RCT) showed that S100ß (SMD: 37.31, 95% CI: 30.97-43.64) and NSE (SMD: 3.50, 95% CI: 2.71-4.28) in the POCD group were significantly higher than in the non-POCD group. The pooled data of observational studies by postoperative sampling time showed significantly higher levels of the following biomarkers in the POCD groups than in the control groups: S100ß levels at 1 hour (SMD: 1.35, 95% CI: 0.07-2.64), 2 days (SMD: 27.97, 95% CI: 25.01-30.94), and 9 days (SMD: 6.41, 95% CI: 5.64-7.19); NSE levels at 1 hour (SMD: 0.92, 95% CI: 0.25-1.60), 6 hours (SMD: 0.79, 95% CI: 0.12-1.45), and 24 hours (SMD: 0.84, 95% CI: 0.38-1.29); and Aß levels at 24 hours (SMD: 2.30, 95% CI: 1.54-3.06), 2 days (SMD: 2.30, 95% CI: 1.83-2.78), and 9 days (SMD: 2.76, 95% CI: 2.25-3.26). The pooled data of the RCT showed that the following biomarkers were significantly higher in POCD patients than in non-POCD patients: S100ß levels at 2 days (SMD: 37.31, 95% CI: 30.97-43.64) and 9 days (SMD: 126.37, 95% CI: 104.97-147.76) and NSE levels at 2 days (SMD: 3.50, 95% CI: 2.71-4.28) and 9 days (SMD: 8.53, 95% CI: 7.00-10.06). High postoperative levels of S100ß, NSE, and Aß may predict POCD. The relationship between these biomarkers and POCD may be affected by sampling time.

Dual roles of anesthetics in postoperative cognitive dysfunction: Regulation of microglial activation through inflammatory signaling pathways.

Postoperative cognitive dysfunction (POCD) is a prevalent clinical entity following surgery and is characterized by declined neurocognitive function. Neuroinflammation mediated by microglia is the essential mechanism of POCD. Anesthetics are thought to be a major contributor to the development of POCD, as they promote microglial activation and induce neuroinflammation. However, this claim remains controversial. Anesthetics can exert both anti- and pro-inflammatory effects by modulating microglial activation, suggesting that anesthetics may play dual roles in the pathogenesis of POCD. Here, we review the mechanisms by which the commonly used anesthetics regulate microglial activation via inflammatory signaling pathways, showing both anti- and pro-inflammatory properties of anesthetics, and indicating how perioperative administration of anesthetics might either relieve or worsen POCD development. The potential for anesthetics to enhance cognitive performance based on their anti-inflammatory properties is further discussed, emphasizing that the beneficial effects of anesthetics vary depending on dose, exposure time, and patients' characteristics. To minimize the incidence of POCD, we recommend considering these factors to select appropriate anesthetics.

Damage-induced NAD release activates intestinal CD4+ and CD8+ T cell via P2X7R signaling.

BACKGROUND: Postoperative ileus (POI) is characterized by the activation of inflammation triggered by tissue damage. Damage-associated molecular patterns (DAMPs) reportedly induce local inflammation after injury. However, the impact of DAMPs on intestinal resident lymphocytes during POI remains poorly elucidated. METHODS: POI in mice was induced via intestinal manipulation (IM). The concentration of nicotinamide adenine dinucleotide (NAD) was detected after IM. The gastrointestinal motility of the mice was assessed after IM or NAD injection. Cytokine production and calcium influx in T cells were investigated after NAD stimulation using flow cytometry. RESULTS: The concentration of extracellular NAD significantly increased after IM administration, and NAD directly impaired gastrointestinal motility. Intraperitoneal injection of NAD promoted the expression of TNF-α in intestinal CD8+ and CD4+ T cells, but only IFN-γ production by CD8+ T cells was significantly promoted by NAD injection. Granzyme B production in CD8+ and CD4+ T cells decreased after administration. Concordantly, the same results were observed in NAD stimulation of intestinal CD3+ T cells in vitro. Blocking the P2X7R-related membrane enzyme ART2.2 significantly diminished the pro-inflammatory effect of NAD. CONCLUSION: IM includes the release of NAD derived from damaged tissues, consequently promoting pro-inflammatory cytokine production in intestinal CD4+ and CD8+ T lymphocytes. NAD-induced intestinal T cells activation may be associated with POI progression in the mouse.

Protein kinase D1 promotes the survival of random-pattern skin flaps in rats.

BACKGROUND: In reconstructive surgery, random skin flaps are commonly used tools to cover skin defects, however, their applicability and size are limited by post-operative complications such as marginal ischemia-reperfusion injury and flap necrosis. Protein kinase D1 (PKD1), a calcium/calmodulin-dependent serine/threonine kinase, is known to induce angiogenesis and has been shown to mitigate ischemia in cardiovascular diseases. However, the role of PKD1 has not been investigated in skin flaps. METHOD: Seventy-five male Sprague-Dawley rats with skin flaps were randomly divided into three groups: control, PKD1, and CID755673. Seven days following surgery, we assessed the general view and survival rate of the flap using histological analysis. Laser Doppler and lead oxide/gelatin angiography were used to evaluate microcirculation blood flow. Histopathological changes, neovascularization and microvascular density (MVD). were examined and calculated using microscopy after H&E staining. Protein expression levels were determined using immunoblotting and immunohistochemistry techniques. RESULT: PKD1 significantly improved flap survival by upregulating angiogenic factors VEGF and cadherin5 and increasing antioxidant enzymes SOD, eNOS, and HO1, as well as reducing caspase 3, cytochrome c, and Bax expression, and attenuating IL-1ß, IL-6, and TNF-α. In the PKD1 group, PKD1 increased neovascularization, and blood flow and flap survival areas were larger as compared to the control and CID755673 groups. CONCLUSION: These findings show that PKD1 accelerates angiogenesis, reduces oxidative stress, and impedes apoptosis and inflammation, thus resulting in improved flap survival. Our observations indicated that PKD1 could be a therapeutic target for flap failure treatment.

Weight regain and the metabolic profile of women in the postoperative period of bariatric surgery: a multivariate analysis / Reganho de peso e perfil metabólico de mulheres no pós-operatório de cirurgia bariátrica: análise multiariada

ABSTRACT BACKGROUND: Weight regain in the postoperative period after bariatric surgery is directly related to the relapse of preoperative comorbidities and a negative impact on the patients' biochemical profile. AIMS: To assess the metabolic impact of weight regain on preoperative comorbidities and on patients' biochemical profiles, in order to show the impact of the complications on the metabolic outcomes of bariatric surgery. METHODS: A retrospective study was carried out with 75 women in the late postoperative period of bariatric surgery who presented pathological weight regain (≥20% of the maximum weight loss). Data of interest consisted of glycemic, lipid, and inflammatory profile measurements at three different moments of evaluation: preoperative period, at the weight nadir (minimum weight), and after weight regain. A multivariate analysis was performed. RESULTS: The mean age was 46.39±12.09 years. Preoperative body mass index was 40.10±4.11 kg/m2. There was an overall increase of 3.36 points in the mean body mass index between the nadir and after regain: from 26.30±3.9 kg/m2 to 29.66±4.66 kg/m2. The mean time to reach the nadir was 18±7.6 months, with an average percentage of excess weight loss of 91.08±11.8%. The median time for pathological weight regain was 48 months, and the mean regain amongst the sample was 8.85±5.65 kg. There was a significant correlation between pathological weight regain and levels of insulin (r=0.351; p<0.011), C-peptide (r=0.303; p<0.011), C-reactive protein (r=0.402; p<0.001), and vitamin D (r=-0.435; p<0.001), the last two being the most influenced by the percentage of weight regained. CONCLUSIONS: The pathological weight regain in the postoperative period of bariatric surgery results in losses in the patients' metabolic and inflammatory profiles. However, the biochemical benefits are sustained up to the preoperative levels of the parameters analyzed.

RESUMO RACIONAL: Reganho de peso no pós-operatório de cirurgia bariátrica está diretamente relacionado à recidiva das comorbidades pré-operatórias e a um impacto negativo no perfil bioquímico desses pacientes. OBJETIVOS: avaliar o impacto metabólico do reganho de peso nas comorbidades pré-operatórias e no perfil bioquímico desses pacientes, a fim de mostrar o impacto das complicações nos desfechos metabólicos finais da cirurgia bariátrica. MÉTODOS: Estudo retrospectivo que analisou 75 mulheres no pós-operatório tardio de cirurgia bariátrica que apresentaram reganho patológico de peso (=20% do máximo de peso perdido). Foram coletados dados referentes às medidas dos perfis glicêmico, lipídico e inflamatório em três momentos distintos de avaliação: no pré-operatório, no nadir de peso (menor peso) e após o reganho ponderal. Foi realizada uma análise multivariada. RESULTADOS: A idade média foi 46.39±12.09 anos. IMC médio pré-operatório foi 40.10±4.11 kg/m2. Houve um aumento de 3,36 pontos no IMC médio entre o nadir e após reganho: de 26.30±3.9 Kg/m2 para 29.66±4.66 Kg/m2. O tempo médio para atingir o nadir foi de 18±7.6 meses, com uma %PEP de 91.08±11.8%. O tempo médio para o reganho patológico foi de 48 meses, e a média de reganho foi 8.85±5.65 kg. Houve correlação significativa entre o reganho patológico e os níveis de insulina (r=0.351; p<0.011), peptídeo C (r=0.303; p<0.011), proteína C reativa (r=0.402; p<0.001) e vitamina D (r=-0.435; p<0.001), sendo os dois últimos os mais influenciados pela porcentagem de reganho de peso. CONCLUSÕES: O reganho de peso patológico no pós-operatório de cirurgia bariátrica resulta em prejuízos ao perfil metabólico e inflamatório dos pacientes. No entanto, os benefícios bioquímicos perduram em relação aos níveis pré-operatórios dos parâmetros analisados

Esketamine alleviates postoperative cognitive decline via stimulator of interferon genes/ TANK-binding kinase 1 signaling pathway in aged rats.

BACKGROUND: Postoperative cognitive decline (POCD) is a common complication after surgery and anesthesia among the elderly. Yet the potential mechanism of POCD remains ambiguous, with limited therapeutic measures currently available. Ketamine has been reported to attenuate POCD after cardiac surgery. Herein, we tried to determine the effect of esketamine (the S-enantiomer of ketamine) on POCD and the possible molecular mechanisms. METHODS: We investigated the effects of esketamine (10 mg/kg) on POCD using an exploratory laparotomy model in aged SD rats (24 months). Open field, novel object recognition, and morris water maze tests were performed on day 30 post-surgery. 24 h or 30 d post-surgery, brain tissue from the hippocampus and ventromedial prefrontal cortex (vmPFC) was harvested and subjected to histopathology and molecular biology analysis. During the in vitro experiment, primary astrocytes from the hippocampus and vmPFC were exposed to lipopolysaccharide (LPS) to investigate the pathological changes in astrocytes during the process of POCD. RESULTS: Our results indicated that exploratory laparotomy could induce significant cognitive and memory decline, accompanied by A2-type astrocytes phenotype loss and increased expression of neuron Aß-42, astrocytes GABA, stimulator of interferon genes (STING) and TANK-binding kinase 1 (TBK1). In addition, LPS exposure significantly decreased the mitochondrial membrane potential and upregulated the level of pyroptosis-associated proteins, including cleaved caspase-1 and IL-18. Notably, treatment with esketamine reversed these abnormalities in vivo and vitro. However, ADU-S100, a special STING activator, suppressed the protective effects of esketamine to a certain extent. Finally, C-176, an antagonist of STING, further enhanced the protective effects of esketamine against POCD. CONCLUSIONS: Findings of our study suggest that esketamine can alleviate surgery-induced POCD in rats via inhibition of the STING/TBK1 signaling pathway.

Ginkgolide B improved postoperative cognitive dysfunction by inhibiting microgliosis-mediated neuroinflammation in the hippocampus of mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) are a common complication of the central nervous system following surgery and anesthesia. The specific pathogenesis and effective therapeutics of POCD need to be further studied. Ginkgolide B (GB), a platelet-activating factor receptor-specific antagonist, has been suggested to have strong anti-inflammatory effects. Here we tested the effects and mechanism of GB on POCD of aged rats. METHODS: Neurobehavioral tests were used to investigate the effect of GB pretreatment on POCD. The hippocampus were harvested to test the expression of proinflammatory cytokines by ELISA. The expression of the microglial marker ionized calcium-binding adaptor molecule-1 (Iba-1) in the hippocampus was evaluated by western blot assay and immunohistochemistry. A Nissl staining experiment was used to detect the neuronal numbers in the hippocampus. RESULTS: Surgery might result in the overexpression of platelet activating factor (PAF) in the plasma and hippocampus and might cause hippocampus-dependent memory impairment. GB pretreatment, inhibited the activation of microglia, reduced the levels of IL-1ß and TNF-α, decreased the loss of neurons after surgery, and prevented POCD in aged rats. CONCLUSION: Our findings suggested that PAF was involved in the development of POCD. Improvement of POCD by PAF antagonist GB was associated with the inhibition of microgliosis-mediated neuroinflammation and neuronal apoptosis in aged rats.

Acute peri-operative neurocognitive disorders: a narrative review.

Peri-operative neurocognitive disorders are the most common complication experienced by older individuals undergoing anaesthesia and surgery. Peri-operative neurocognitive disorders, particularly postoperative delirium, result in long-term poor outcomes including: death; dementia; loss of independence; and poor cognitive and functional outcomes. Recent changes to the nomenclature of these disorders aims to align peri-operative neurocognitive disorders with cognitive disorders in the community, with consistent definitions and clinical diagnosis. Possible mechanisms include: undiagnosed neurodegenerative disease; inflammation and resulting neuroinflammation; neuronal damage; and comorbid systemic disease. Pre-operative frailty represents a significant risk for poor postoperative outcomes; it is associated with an increase in the incidence of cognitive decline at 3 and 12 months postoperatively. In addition to cognitive decline, frailty is associated with poor functional outcomes following elective non-cardiac surgery. It was recently shown that 29% of frail patients died or experienced institutionalisation or new disability within 90 days of major elective surgery. Identification of vulnerable patients before undergoing surgery and anaesthesia is the key to preventing peri-operative neurocognitive disorders. Current approaches include: pre-operative delirium and cognitive screening; blood biomarker analysis; intra-operative management that may reduce the incidence of postoperative delirium such as lighter anaesthesia using processed electroencephalography devices; and introduction of guidelines which may reduce or prevent delirium and postoperative neurocognitive disorders. This review will address these issues and advocate for an approach to care for older peri-operative patients which starts in the community and continues throughout the pre-operative, intra-operative, postoperative and post-discharge phases of care management, involving multidisciplinary medical teams, as well as family and caregivers wherever possible.

A single-center experience of parathyroidectomy in 1500 cases for secondary hyperparathyroidism: a retrospective study.

BACKGROUND: Chronic kidney disease (CKD) is a global public health problem. With the deterioration of renal function, a certain proportion of CKD patients enter the uremic stage, and secondary hyperparathyroidism (SHPT) becomes a challenge. For refractory hyperparathyroidism, parathyroidectomy (PTX) plays a key role in reducing mortality and improving prognosis. Nevertheless, no consensus has been reached on the optimal surgical method. We aimed to provide evidence for the effectiveness of surgical treatment by summarizing the experience from our center. METHODS: Clinical data from 1500 patients undergoing parathyroidectomy were recorded, which included 1419 patients in a total parathyroidectomy without autotransplantation (tPTX) group, 54 patients in a total parathyroidectomy plus autotransplantation (tPTX + AT) group, and 27 patients in the other group. Perioperative basic data, intact parathyroid hormone (i-PTH) levels, serum calcium levels, serum phosphorus levels, pathological reports, coexisting thyroid diseases, short-term outcomes and complications were analyzed. Moreover, postoperative complications were compared between the tPTX and tPTX + AT groups. RESULTS: Parathyroid hormone, serum calcium and phosphorus levels decreased significantly post-surgery. Two patients died during the perioperative period. As the two most common complications, the incidences of severe hypocalcemia and hyperkalemia were 36.20% (543 cases) and 24.60% (369 cases), respectively. Pre-iPTH levels (OR = 1.001, 95% CI: 1.001-1.001, p < 0.01), serum alkaline phosphatase (ALP) levels (OR = 1.002, 95% CI: 1.001-1.002, p < 0.01) and the mass of excised parathyroid gland (OR = 3.06, 95% CI: 1.24-7.55, p = 0.02) were positively associated with postoperative severe hypocalcemia, while age and serum calcium were negatively associated with it. Pathological reports of resected parathyroid and thyroid glands indicated that 96.49% had parathyroid nodular hyperplasia, 13.45% had thyroid nodular hyperplasia, and 4.08% had thyroid papillary carcinoma. CONCLUSIONS: Parathyroidectomy is a safe and effective treatment for refractory secondary hyperparathyroidism. Severe hypocalcemia is the main complication, and coexistent thyroid diseases should never be neglected.

Protective effect of MiR-146 on renal injury following cardiopulmonary bypass in rats through mediating NF-κB signaling pathway.

The mechanism of renal injury after cardiopulmonary bypass is not clear, and the protective effect of microRNA-146 through mediating NF KB signaling pathway needs to be verified. The study intends to establish a rat model of cardiopulmonary bypass (CPB). MiR-146 is silenced or overexpressed by lentivirus transfection. It is divided into miR-146 inhibitors group (inhibitors), miR-146 mimics group (mimics) and sham group. It is found that the contents of Cr, bun and MDA in blood = , serum IL-1, IL-6 and TNF in mimics group are higher than those in the other two groups- α Content, apoptosis rate, ICAM-1, TNF- α, NF- κ B mRNA and NF- κ B protein decreased significantly (P < 0.05), while the content of SOD in kidney increased significantly (P < 0.05). In the inhibitors group, the above indicators showed the opposite results. Double luciferase assay showed that NF-kB was the target gene of miR-146. It can be seen that the expression of miR-146 inhibits inflammatory factors, apoptosis, oxidative stress and NF- κ the activation of B pathway promotes the repair of renal injury in CPB rats.

Propofol ameliorates acute postoperative fatigue and promotes glucagon-regulated hepatic gluconeogenesis by activating CREB/PGC-1α and accelerating fatty acids beta-oxidation.

Postoperative fatigue (POF) is the most common and long-lasting complication after surgery, which brings heavy burden to individuals and society. Recently, hastening postoperative recovery receives increasing attention, but unfortunately, the mechanisms underlying POF remain unclear. Propofol is a wildly used general anesthetic in clinic, and inspired by the rapid antidepressant effects induced by ketamine at non-anesthetic dose, the present study was undertaken to investigate the anti-fatigue effects and underlying mechanisms of propofol at a non-anesthetic dose in 70% hepatectomy induced POF model in rats. We first showed here that single administration of propofol at 0.1 mg/kg ameliorated acute POF in hepatectomy induced POF rats. Based on metabonomics analysis, we hypothesized that propofol exerted anti-fatigue activity in POF rats by facilitating free fatty acid (FFA) oxidation and gluconeogenesis. We further confirmed that propofol restored the deficit in FFA oxidation and gluconeogenesis in POF rats, as evidenced by the elevated FFA utilization, acetyl coenzyme A content, pyruvic acid content, phosphoenolpyruvic acid content, hepatic glucose output and glycogen storage. Moreover, propofol stimulated glucagon secretion and up-regulated expression of cAMP-response element binding protein (CREB), phosphorylated CREB, peroxlsome prolifeator-activated receptor-γ coactivator-1α (PGC-1α), phosphoenolpyruvate carboxykinade1 and carnitine palmitoltransferase 1A. In summary, our study suggests for the first time that propofol ameliorates acute POF by promoting glucagon-regulated gluconeogenesis via CREB/PGC-1α signaling and accelerating FFA beta-oxidation.