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.

Preoperative prognostic nutritional index value as a predictive factor for postoperative delirium in older adult patients with hip fractures: a secondary analysis.

BACKGROUND: Malnutrition is a common geriatric syndrome and can be targeted preoperatively to decrease the risk of postoperative delirium (POD) in older adult patients. To analyze the value of the prognostic nutritional index (PNI) to predict the incidence of POD in older adult patients with hip fractures. METHODS: This was a prospective, observational, cohort study of older adult patients with hip fractures. Preoperative PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/µL) using preoperative laboratory results. Patients were divided into POD and non-POD groups using the Confusion Assessment Method (CAM). The risk factors associated with POD as well as the relationship between PNI values and the incidence of POD were analyzed using univariate and multivariate logistic regression analyses. The predictive value of PNI for POD was assessed using receiver operating characteristic curve analysis. RESULTS: In this cohort of 369 patients who underwent hip fracture surgery, 67 patients (18.2%) were diagnosed with POD by the CAM results. Low PNI increased the risk of POD (odds ratio (OR) = 0.928, 95% confidence interval (CI): 0.864-0.997). General anesthesia (OR = 2.307, 95% CI: 1.279-4.162) and Mini-Mental State Examination (MMSE) score (OR = 0.956, 95% CI: 0.920-0.994) were also identified as risk factors for POD. Receiver operating characteristic curve analysis suggested that PNI combined with the anesthetic method and MMSE score may be used as a potential predictive indicator of POD after hip fracture surgery. CONCLUSION: Preoperative PNI value is related to POD in older adult patients with hip fractures. TRIAL REGISTRATION: This secondary analysis study was approved by the Peking University Third Hospital Medical Science Research Ethics Committee (approval No. M2022578) and registered in the Chinese Clinical Trial Registry (ChiCTR2300070569).

A Bibliometric Analysis for Low-Intensity Ultrasound Study Over the Past Three Decades.

Low-intensity ultrasound (LI-US) is a non-invasive stimulation technique that has emerged in recent years and has been shown to have positive effects on neuromodulation, fracture healing, inflammation improvement, and metabolic regulation. This study reports the conclusions of a bibliometric analysis of LI-US. Input data for the period between 1995 and 2022, including 7209 related articles in the field of LI-US, were collected from the core library of the Web of Science (WOS) database. Using these data, a set of bibliometric indicators was obtained to gain knowledge on different aspects: global production, research areas, and sources analysis, contributions of countries and institutions, author analysis, citation analysis, and keyword analysis. This study combined the data analysis capabilities provided by the WOS database, making use of two bibliometric software tools: R software and VOS viewer to achieve analysis and data exploration visualization, and predicted the further development trends of LI-US. It turns out that the United States and China are co-leaders while Zhang ZG is the most significant author in LI-US. In the future, the hot spots of LI-US will continue to focus on parameter research, mechanism discussion, safety regulations, and neuromodulation applications.

Low-Intensity Pulsed Ultrasound Attenuates Postoperative Neurocognitive Impairment and Salvages Hippocampal Synaptogenesis in Aged Mice.

Postoperative neurocognitive impairment is an urgent problem with global aging accelerating. The prevention and treatment of postoperative neurocognitive impairment have been widely investigated but lack effective strategies. Low-intensity pulsed ultrasound (LIPUS), a non-invasive tool, has shown an effect on neuroprotection, but whether it could attenuate the postoperative neurocognitive impairment and the underlying mechanisms remains unknown. An experimental setup for LIPUS stimulation of the hippocampus was well established. A laparotomy model in aged mice was applied, and a Morris water maze was used to assess cognitive function. RT-qPCR and western blotting were used to detect levels of Piezo1, synapse-associated proteins in the hippocampus, respectively. Immunofluorescent staining was also used to determine the neural activation and Piezo1 expression. The results showed that LIPUS increased synapse-related proteins of the hippocampus and attenuated cognitive impairment in aged mice. Meanwhile, LIPUS suppressed the overexpression of Piezo1 in the hippocampus. We further found that LIPUS promoted Calpain1 activity and increased extracellular regulated protein kinases (Erk) phosphorylation. Our results suggested that LIPUS could improve cognitive impairment and increase hippocampal synaptogenesis through the Piezo1-mediated Calpain1/ Erk pathway. LIPUS could be used as an effective physical intervention to alleviate postoperative cognitive dysfunction in the aged population.

Angulation error assessment for the trajectory in the anteroposterior and lateral fluoroscopic views during percutaneous endoscopic transforaminal lumbar discectomy.

BACKGROUND: Anteroposterior (AP) and lateral fluoroscopies are often used to evaluate the intraoperative location and angulation of the trajectory in percutaneous endoscopic transforaminal lumbar discectomy (PETLD). Although the location of the trajectory shown in fluoroscopy is absolutely accurate, the angulation is not always reliable. This study aimed to evaluate the accuracy of the angle shown in the AP and lateral fluoroscopic views. METHODS: A technical study was performed to assess the angulation errors of PETLD trajectories shown in AP and lateral fluoroscopic views. After reconstructing a lumbar CT image, a virtual trajectory was placed into the intervertebral foramen with gradient-changing coronal angulations of the cephalad angle plane (CACAP). For each angulation, virtual AP and lateral fluoroscopies were taken, and the cephalad angles (CA) of the trajectory shown in the AP and lateral fluoroscopic views, which indicated the coronal CA and the sagittal CA, respectively, were measured. The angular relationships among the real CA, CACAP, coronal CA, and sagittal CA were further demonstrated with formulae. RESULTS: In PETLD, the coronal CA is approximately equal to the real CA, with a small angle difference and percentage error, whereas the sagittal CA shows a rather large angle difference and percentage error. CONCLUSION: The AP view is more reliable than the lateral view in determining the CA of the PETLD trajectory.

Reciprocal interaction between mitochondrial fission and mitophagy in postoperative delayed neurocognitive recovery in aged rats.

INTRODUCTION: Emerging evidence suggests that mitochondrial dysfunction plays a crucial role in the pathogenesis of postoperative delayed neurocognitive recovery (dNCR). Mitochondria exist in a dynamic equilibrium that involves fission and fusion to regulate morphology and maintains normal cell function via the removal of damaged mitochondria through mitophagy. Nonetheless, the relationship between mitochondrial morphology and mitophagy, and how they influence mitochondrial function in the development of postoperative dNCR, remains poorly understood. Here, we observed morphological alterations of mitochondria and mitophagy activity in hippocampal neurons and assessed the involvement of their interaction in dNCR following general anesthesia and surgical stress in aged rats. METHODS: Firstly, we evaluated the spatial learning and memory ability of the aged rats after anesthesia/surgery. Hippocampal mitochondrial function and mitochondrial morphology were detected. Afterwards, mitochondrial fission was inhibited by Mdivi-1 and siDrp1 in vivo and in vitro separately. We then detected mitophagy and mitochondrial function. Finally, we used rapamycin to activate mitophagy and observed mitochondrial morphology and mitochondrial function. RESULTS: Surgery impaired hippocampal-dependent spatial learning and memory ability and caused mitochondrial dysfunction. It also increased mitochondrial fission and inhibited mitophagy in hippocampal neurons. Mdivi-1 improved mitophagy and learning and memory ability of aged rats by inhibiting mitochondrial fission. Knocking down Drp1 by siDrp1 also improved mitophagy and mitochondrial function. Meanwhile, rapamycin inhibited excessive mitochondrial fission and improved mitochondrial function. CONCLUSION: Surgery simultaneously increases mitochondrial fission and inhibits mitophagy activity. Mechanistically, mitochondrial fission/fusion and mitophagy activity interact reciprocally with each other and are both involved in postoperative dNCR. These mitochondrial events after surgical stress may provide novel targets and modalities for therapeutic intervention in postoperative dNCR.

Preoperative serum ribose concentrations may be associated with postoperative delirium in older patients with a hip fracture.

BACKGROUND: Postoperative delirium (POD) is a common postoperative neurocognitive complication, especially in older patients. However, satisfactory biomarkers for predicting individual risks of POD have not been confirmed. D-ribose involvement in protein glycation and aggregation plays a pivotal role in age-related neurodegenerative disorders such as Alzheimer's disease. OBJECTIVES: This study aimed to determine whether serum D-ribose concentrations contribute to the early diagnosis of POD. We also discuss the probable mechanisms underlying the development of POD. METHODS: 110 older patients with hip fracture who had undergone internal fixation or hip replacement under general anesthesia and had completed our assessments were selected. Preoperative venous blood (4 ml) was collected before the induction of anesthesia. Postoperative venous blood was obtained at 07:00 and 20:00 h on postoperative day 1 and at 20:00 h on postoperative day 2. On the first 2 postoperative days, the patients were assessed twice daily (at 8:00 and 20:00 h on each day) using the Confusion Assessment Method-Chinese Revision. RESULTS: 15 patients were finally diagnosed with POD. We also included 15 patients without POD who were matched with the recruited patients with POD (1:1) on the basis of age, sex, body mass index and the Mini-Mental State Examination score. Serum ribose concentrations were measured by high-performance liquid chromatography. The demographic characteristics of the groups were matched. Preoperative serum ribose concentrations were significantly higher in patients with POD than in those without POD (p < 0.05) and were also an independent risk factor for POD. Moreover, when the preoperative serum ribose concentration doubled, the risk of POD increased by 1.672 times. CONCLUSIONS: These results indicate that the serum D-ribose concentration may be a potential predictive molecular biomarker for POD, and provide useful information for further pathological mechanism studies.

A Randomized Study on the Prophylactic Use of Acetaminophen to Prevent Fever after the Removal of Drainage Tubes for Lumbar Surgery.

BACKGROUND: Many inpatients encounter a fever in the first 24 h after drainage removal. It is costly to exclude the possibility of deep infection and cultures usually fail to identify the etiology. We hypothesize that the fever is caused by a normal inflammatory response and tested whether the prophylactic use of acetaminophen could reduce the fever rate. METHODS: This was a prospectively randomized clinical trial performed from July 2019 to January 2020. A total of 183 consecutive patients undergoing lumbar spine surgery were prospectively randomized into two groups. Ninety-one patients were randomized into the study group; they received oral acetaminophen before removal of the drainage tubes and a second dose at 8 p.m. on the same day. The remaining 92 patients were placed in the control group, and they were given routine treatment without acetaminophen. The two groups were compared for differences in age, sex, height, weight, BMI, surgical segments, surgical time, blood loss, blood transfusion, ASA score, duration of drainage, total volume of the drainage, variation of WBC and CRP, hospital stay after the removal of the drainage tube and the rate of fever. Student's t-test and the Mann-Whitney U test were used to analyze the continuous data, while the chi-square test was used for the analysis of the ranked data. RESULTS: Regarding the comparisons of basic information, there were no significant differences between the two groups for age, height, weight, BMI, surgical segments, surgical time, blood loss, blood transfusion, total drainage volume, duration of drainage, hospital stay, WBC, and CRP variation or the duration of hospital stay after removal of the drainage tube (all p > 0.05). However, the fever rate was significantly different (p = 0.006), and the fever rate of the study group (14/91, 15.38%) was significantly lower than that of the control group (30/92, 32.61%). In the study group, there were no complications related to the use of acetaminophen during the hospital stay or during the outpatient follow-up period. CONCLUSION: Fever after removal of tube drainage is caused by a normal inflammatory response, and a small dose of acetaminophen could significantly reduce the possibility of fever.

Preoperative plasma visfatin may have a dual effect on the occurrence of postoperative delirium.

Background: Visfatin is considered to be a "novel pro-inflammatory cytokine." Neuroinflammatory response is one of the important mechanisms of postoperative delirium (POD). The relationship between preoperative plasma visfatin and POD is unclear. Objective: To investigate the relationship between preoperative plasma visfatin concentrations and POD (primary outcome) in older hip fracture patients and to explore whether it affects POD through inflammatory factors. Materials and methods: This prospective cohort study enrolled 176 elderly patients who were scheduled for hip fracture surgery. Preoperative plasma was collected on the morning of surgery, and visfatin levels were measured. Interleukin (IL)-1 and IL-6 were measured using patients' plasma collected on the first day after surgery. We used the 3-min diagnostic interview for Confusion Assessment Method-defined delirium (3D-CAM) twice daily within the 2 days after surgery to assess whether POD had occurred. Restricted cubic splines and piecewise regression were used to explore the relationship between preoperative plasma visfatin concentrations and POD, and further mediation analysis was used to verify whether visfatin plays a role in POD through regulating inflammatory factors. Results: The incidence of POD was 18.2%. A J-shaped association was observed between preoperative plasma visfatin levels and POD. The risk of POD decreased within the lower visfatin concentration range up to 37.87 ng/ml, with a hazard ratio of 0.59 per 5 ng/ml [odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.37-0.95], but the risk increased above this concentration (P for non-linearity < 0.001, with a hazard ratio of 1.116 per 10 ng/ml; OR = 1.10, 95% CI = 1.02-1.23). Mediation effect analysis showed that when the plasma visfatin concentration was higher than 37.87 ng/ml, the effect of visfatin on POD was mediated by IL-6 (p < 0.01). A significant indirect association with postoperative plasma IL-6 was observed between preoperative plasma visfatin and POD (adjusted ß = 0.1%; 95% CI = 4.8∼38.9%; p < 0.01). Conclusion: Visfatin is the protective factor in POD when the preoperative plasma visfatin concentration is below 37.87 ng/ml, but when it exceeds 37.87 ng/ml, the visfatin concentration is a risk factor for POD, which is mediated by postoperative plasma IL-6. The results suggest that preoperative visfatin may have a dual effect on the POD occurrence. Clinical trial registration: [www.ClinicalTrials.gov], identifier [ChiCTR21 00052674].

Type 2 Diabetes Mellitus with Tight Glucose Control and Poor Pre-Injury Stair Climbing Capacity May Predict Postoperative Delirium: A Secondary Analysis.

(1) Background: Previous evidence demonstrates that tight glycemic control and good physical function could reduce the risk of delirium. This study aimed to investigate whether the occurrence of postoperative delirium (POD) in older hip fracture surgery patients is associated with preoperative glycemic control factors or pre-injury physical performance. (2) Methods: Three-hundred and nine individuals aged over 65 years and scheduled for hip fracture surgery were included at a single center. Glycemic control factors and pre-injury physical performance were assessed preoperatively. The presence of delirium was assessed using the Confusion Assessment Method on postoperative hospitalization days. Univariate and multivariable logistic regression models and a risk prediction model of POD were established. (3) Results: Among the 309 patients, 52 (16.83%) experienced POD during the hospital stay. The numbers of pre-injury physical performance and type 2 diabetes mellitus (T2DM) patients were significantly different in the POD and non-POD groups. The multivariable model showed that development of delirium was significantly explained by preoperative fasting blood glucose (FBG) (OR 0.804, p = 0.004), stair climbing (OR 0.709, p = 0.003), T2DM (odds ratio (OR) 3.654, p = 0.001), and age-adjusted Charlson comorbidity index (ACCI) (OR 1.270, p = 0.038). The area under the receiver operating characteristic curve (AUROC) of the risk prediction model including those covariates was 0.770. (4) Conclusions: More older T2DM patients develop POD after hip fracture surgery than patients without T2DM. A simple assessment of preoperative FBG and pre-injury stair climbing capacity may identify those at high risk for the development of POD. Higher preoperative FBG and good pre-injury stair climbing capacity are protective factors for POD.

Delayed aortoesophageal and tracheoesophageal fistulas secondary to foreign body ingestion: a case report.

Ingestion of a foreign body (FB) is a common condition with a few potentially life-threatening complications, including esophageal perforation (EP), aortoesophageal fistula (AEF), mediastinal infection, and tracheoesophageal fistula (TEF). In this case, a patient who accidentally ingested a duck bone gradually experienced all of the above complications. To resolve the symptom of difficulty swallowing, the patient underwent emergency treatment for removal of the esophageal FB via endoscopic surgery. Under endoscopy, esophageal mucosal injuries were present, but no other abnormalities, such as active bleeding, were observed. However, the patient returned to our hospital a week later with symptoms of vomiting and black stool and received the diagnosis of EP, AEF and mediastinal infection. Two days later, he vomited 1,000-2,000 mL of blood after experiencing sudden severe chest pain. Then, thoracic endovascular aortic repair (TEVAR) and mediastinal drainage with video-assisted thoracoscopic surgery (VATS) were performed under emergency general anesthesia. Additionally, the patient underwent esophageal stent implantation when TEF was confirmed by tracheal computed tomography (CT). The patient was treated with anti-infective therapy throughout the treatment process. Finally, he recovered and was able to tolerate a liquid diet. Comprehensive evaluation and multidisciplinary cooperation are all very important for the treatment of esophageal foreign bodies and complications.

The Role of Fecal Fusobacterium nucleatum and pks+ Escherichia coli as Early Diagnostic Markers of Colorectal Cancer.

BACKGROUND: Accurate analysis of intestinal microbiota will facilitate establishment of an evaluating system for assessing colorectal cancer (CRC) risk and prognosis. This study evaluates the potential role of Fusobacterium nucleatum (F. nucleatum) and Escherichia coli with a pks gene (pks+ E. coli) in early CRC diagnosis. METHODS: We recruited 139 patients, including CRC (n = 60), colorectal adenomatous polyposis (CAP) (n = 37), and healthy individuals (n = 42) based on their colonoscopy examinations. We collected stool and serum samples from the participants and measured the relative abundance of F. nucleatum and pks+ E. coli in fecal samples by quantitative PCR. Receiver operating characteristic curve (ROC) analyses were used to analyze the diagnostic value of single or combined biomarkers. RESULTS: Fecal F. nucleatum and pks+ E. coli levels were higher in the CRC group in either the CAP group or healthy controls (P = 0.02; 0.01). There was no statistical difference in the distribution of F. nucleatum and pks+ E. coli in patients with different tumor sites (P > 0.05). The combination of F. nucleatum+pks+ E. coli+CEA+CA19-9+FOBT was chosen as the optimal panel in differentiating both CRC and CAP from the controls. The combination of F. nucleatum, pks+ E. coli, and FOBT improved diagnostic efficiency. However, there was difficulty in differentiating CRC from CAP. CONCLUSION: Our results suggested that combining bacterial markers with conventional tumor markers improves the diagnostic efficiency for noninvasive diagnosis of CRC.

Predictive Value of Preoperative Profiling of Serum Metabolites for Emergence Agitation After General Anesthesia in Adult Patients.

Background: Emergence agitation (EA) in adult patients under general anesthesia leads to increased postoperative complications and heavy medical burden. Unfortunately, its pathogenesis has not been clarified until now. The purpose of the present study was to explore the relationship between preoperative serum metabolites and EA. Methods: We used an untargeted metabolic analysis method to investigate the different metabolomes in the serum of EA patients and non-EA patients undergoing elective surgical procedures after the induction of general anesthesia. A Richmond Agitation-Sedation Scale score ≥ +2 was diagnosed as EA during postoperative emergence. Non-EA patients were matched with EA patients according to general characteristics. Preoperative serum samples of the two groups were collected to investigate the association between serum metabolites and EA development. Results: The serum samples of 16 EA patients with 34 matched non-EA patients were obtained for metabolic analysis. After screening and alignment with databases, 31 altered metabolites were detected between the two groups. These metabolites were mainly involved in the metabolism of lipids, purines, and amino acids. Analyses of receiver-operating characteristic curves showed that the preoperative alterations of choline, cytidine, glycerophosphocholine, L-phenylalanine, oleamide, and inosine may be associated with adult EA. Conclusion: Multiple metabolic abnormalities (including those for lipids, purines, and amino acids) and other pathological processes (e.g., neurotransmitter imbalance and oxidative stress) may contribute to EA. Several altered metabolites in serum before surgery may have predictive value for EA diagnosis. This study might afford new metabolic clues for the understanding of EA pathogenesis.

Cholecystokinin octapeptide improves hippocampal glutamatergic synaptogenesis and postoperative cognition by inhibiting induction of A1 reactive astrocytes in aged mice.

AIMS: Delayed neurocognitive recovery (dNCR) is a common postoperative complication in geriatric surgical patients for which there is no efficacious therapy. Cholecystokinin octapeptide (CCK-8), an immunomodulatory peptide, regulates memory and learning. Here, we explored the effects and mechanism of action of CCK-8 on dNCR. METHODS: We applied laparotomy to establish a model of dNCR in aged mice. Morris water maze and fear conditioning tests were used to evaluate cognition. Immunofluorescence was used to detect the density of CCK-8, A1 reactive astrocytes, glutamatergic synapses, and activation of microglia in the hippocampus. Quantitative PCR was performed to determine mRNA levels of synapse-associated factors. A1 reactive astrocytes, activated microglia, and glutamatergic synapse-associated protein levels in the hippocampus were assessed by western blotting. RESULTS: Administration of CCK-8 suppressed the activation of microglia, the induction of A1 reactive astrocytes, and the expression of tumor necrosis factor alpha, complement 1q, and interleukin 1 alpha in the hippocampus. Furthermore, it promoted glutamatergic synaptogenesis and neurocognitive recovery in aged dNCR model mice. CONCLUSION: Our findings indicated that CCK-8 alleviated cognitive impairment and promoted glutamatergic synaptogenesis by inhibiting the induction of A1 reactive astrocytes and the activation of microglia. CCK-8 is, therefore, a potential therapeutic target for dNCR.

Inhibition of α-Synuclein Accumulation Improves Neuronal Apoptosis and Delayed Postoperative Cognitive Recovery in Aged Mice.

Delayed neurocognitive recovery (dNCR) is a major complication after anesthesia and surgery in older adults. Alpha-synuclein (α-syn; encoded by the gene, SNCA) has recently been shown to play an important role in hippocampus-dependent working memory. Aggregated forms of α-syn are associated with multiple neurotoxic mechanisms, such as mitochondrial dysfunction and cell death. In this study, we found that blocking α-syn improved both mitochondrial function and mitochondria-dependent neuronal apoptosis in a mouse model of dNCR. Various forms of α-syn (including total α-syn, phosphorylated-Ser129-α-syn, and oligomers) were upregulated in hippocampal tissue and extracted mitochondria after surgical challenge. Clenbuterol is a novel transcription modulator of Scna. Clenbuterol significantly attenuated surgery-induced progressive accumulation of various toxic α-syn forms in the hippocampus, as well as mitochondrial damage and memory deficits in aged mice following surgery. We also observed excessive mitochondrial α-syn accumulation and increased mitochondria-mediated apoptosis in vitro using nerve growth factor-differentiated PC12 cells and primary hippocampal neurons exposed to lipopolysaccharide. To further validate the neuroprotective effect of α-syn inhibition, we used a lentiviral Snca-shRNA (Lv-shSnca) to knockdown Snca. Of note, Lv-shSnca transfection significantly inhibited neuronal apoptosis mediated by the mitochondrial apoptosis pathway in neurons exposed to lipopolysaccharide. This α-syn inhibition improved the disruption to mitochondrial morphology and function, as well as decreased levels of apoptosis. Our results suggest that targeting pathological α-syn may achieve neuroprotection through regulation of mitochondrial homeostasis and suppression of apoptosis in the aged hippocampus, further strengthening the therapeutic potential of targeting α-syn for dNCR.

Full-Endoscopic Foraminotomy with a Novel Large Endoscopic Trephine for Severe Degenerative Lumbar Foraminal Stenosis at L5 S1 Level: An Advanced Surgical Technique.

To (i) introduce the technical notes of a novel full-endoscopic foraminotomy with a large endoscopic trephine for the treatment of severe degenerative lumbar foraminal stenosis at L5 S1 level; (ii) assess the primary clinical outcomes of this technique; (iii) compare the effectiveness of this full-endoscopic foraminotomy technique and other previous techniques for lumbar foraminal stenosis. From January 2019 to August 2019, a retrospective study of L5 S1 severe degenerative lumbar foraminal stenosis was performed in our center. All patients who were diagnosed with severe foraminal stenosis at L5 S1 level and failed conservative treatment for at least 6 weeks were identified. Patients with segmental instability or other coexisting contraindications were excluded. A total of 21 patients were enrolled in the study. All patients were treated by full-endoscopic foraminotomy using large endoscopic trephine. The visual analogue scale (VAS) and Oswestry disability index (ODI) were evaluated preoperatively and at 1, 3, 6 months, and 1 year after the surgery, and the modified MacNab criteria were used to evaluate clinical outcomes at the last follow-up. There were 10 males and 11 females with a mean age of 66.38 ± 9.51 years. Five patients had a history of lumbar surgery. The mean operative time was 63.57 ± 25.74 min. The mean follow-up time was 13.29 ± 1.38 months. The mean postoperative hospital stay time was 1.29 ± 0.56 days. The mean preoperative VAS score significantly decreased from 7.38 ± 1.02 to 2.76 ± 1.09 (t = 19.759, P < 0.01), 2.25 ± 1.02 (t = 21.508, P < 0.01), 1.60 ± 1.05 (t = 31.812, P < 0.01), and 1.45 ± 1.10 (t = 25.156, P < 0.01) at 1 month, 3 months, 6 months, and 1 year after the operation. The mean preoperative ODI score significantly decreased from 64.66% ± 4.91% to 30.69% ± 4.59% (t = 33.724, P < 0.01), 29.44% ± 4.50% (t = 32.117, P < 0.01), 24.22% ± 4.14% (t = 33.951, P < 0.01), and 22.44% ± 4.94% (t = 30.241, P < 0.01) at 1 month, 3 months, 6 months, and 1 year after the operation. At the last follow-up, 19 patients (90.48%) got excellent or good outcomes. One patient suffered postoperative dysesthesia, and the symptoms were controlled by conversion treatment. One patient took revision surgery due to the incomplete decompression. There were no other major complications. Percutaneous endoscopic decompression is minimally invasive spine surgery. However, the application of endoscopic decompression for L5 S1 foraminal stenosis is relatively difficult due to the high iliac crest and narrow foramen. Full-endoscopic foraminotomy with the large endoscopic trephine is an effective and safe technique for the treatment of degenerative lumbar foraminal stenosis.

A Meta-Analysis of Proteomic Blood Markers of Colorectal Cancer.

BACKGROUND: Early diagnosis will significantly improve the survival rate of colorectal cancer (CRC); however, the existing methods for CRC screening were either invasive or inefficient. There is an emergency need for novel markers in CRC's early diagnosis. Serum proteomics has gained great potential in discovering novel markers, providing markers that reflect the early stage of cancer and prognosis prediction of CRC. In this paper, the results of proteomics of CRC studies were summarized through a meta-analysis in order to obtain the diagnostic efficiency of novel markers. METHODS: A systematic search on bibliographic databases was performed to collect the studies that explore blood-based markers for CRC applying proteomics. The detection and validation methods, as well as the specificity and sensitivity of the biomarkers in these studies, were evaluated. Newcastle- Ottawa Scale (NOS) case-control studies version was used for quality assessment of included studies. RESULTS: Thirty-four studies were selected from 751 studies, in which markers detected by proteomics were summarized. In total, fifty-nine proteins were classified according to their biological function. The sensitivity, specificity, or AUC varied among these markers. Among them, Mammalian STE20-like protein kinase 1/ Serine threonine kinase 4 (MST1/STK4), S100 calcium-binding protein A9 (S100A9), and Tissue inhibitor of metalloproteinases 1 (TIMP1) were suitable for effect sizes merging, and their diagnostic efficiencies were recalculated after merging. MST1/STK4 obtained a sensitivity of 68% and a specificity of 78%. S100A9 achieved a sensitivity of 72%, a specificity of 83%, and an AUC of 0.88. TIMP1 obtained a sensitivity of 42%, a specificity of 88%, and an AUC of 0.71. CONCLUSION: MST1/STK4, S100A9, and TIMP1 showed excellent performance for CRC detection. Several other markers also presented optimized diagnostic efficacy for CRC early detection, but further verification is still needed before they are suitable for clinical use. The discovering of more efficient markers will benefit CRC treatment.

Radiological indicators to predict the application of assistant intubation techniques for patients undergoing cervical surgery.

BACKGROUND: We aimed to distinguish the preoperative radiological indicators to predict the application of assistant techniques during intubation for patients undergoing selective cervical surgery. METHODS: A total of 104 patients were enrolled in this study. According to whether intubation was successfully accomplished by simple Macintosh laryngoscopy, patients were divided into Macintosh laryngoscopy group (n = 78) and Assistant technique group (n = 26). We measured patients' radiographical data via their preoperative X-ray and MRI images, and compared the differences between two groups. Binary logistic regression model was applied to distinguish the meaningful predictors. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to describe the discrimination ability of indicators. The highest Youden's index corresponded to an optimal cut-off value. RESULTS: Ten variables exhibited significant statistical differences between two groups (P <  0.05). Based on logistic regression model, four further showed correlation with the application of assistant techniques, namely, perpendicular distance from hard palate to tip of upper incisor (X2), atlanto-occipital gap (X9), angle between a line passing through posterior-superior point of hard palate and the lowest point of the occipital bone and a line passing through the anterior-inferior point and the posterior-inferior point of the second cervical vertebral body (Angle E), and distance from skin to hyoid bone (MRI 7). Angle E owned the largest AUC (0.929), and its optimal cut-off value was 19.9° (sensitivity = 88.5%, specificity = 91.0%). the optimal cut-off value, sensitivity and specificity of other three variables were X2 (30.1 mm, 76.9, 76.9%), MRI7 (16.3 mm, 69.2, 87.2%), and X9 (7.3 mm, 73.1, 56.4%). CONCLUSIONS: Four radiological variables possessed potential ability to predict the application of assistant intubation techniques. Anaesthesiologists are recommended to apply assistant techniques more positively once encountering the mentioned cut-off values.

Building block osteotomy, a new back muscle-preserving laminoplasty for lumbar spinal stenosis.

In order to preserve paravertebral muscles and posterior ligaments complex (PLC), this paper proposes a new lumbar laminoplasty surgery for lumbar spinal stenosis (LSS). According to the anatomy of back muscles insertions, building block osteotomy (BBO) which aimed to achieve precise osteotomy and reconstruction based on modular design theory was firstly put forward, and supposed to be achieved by an ultrasound bone scalpel (UBS). In details, lumbar spinous processes are longitudinally split, then supraspinous and interspinous ligaments are sharply cut off longitudinally. After converting to lumbar flexion, lamina osteotomy is innovatively finished by an UBS through interspinous space. After decompression, hollow screws are firstly suggested to be used on each side to fix lamina and spinous processes, and PLC is reconstructed by interrupted suture. Feasibility of this method is evaluated in details. Challenges, advantages and disadvantages are also discussed.

Neurological manifestations of patients with COVID-19: potential routes of SARS-CoV-2 neuroinvasion from the periphery to the brain.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), has caused a global pandemic in only 3 months. In addition to major respiratory distress, characteristic neurological manifestations are also described, indicating that SARS-CoV-2 may be an underestimated opportunistic pathogen of the brain. Based on previous studies of neuroinvasive human respiratory coronaviruses, it is proposed that after physical contact with the nasal mucosa, laryngopharynx, trachea, lower respiratory tract, alveoli epithelium, or gastrointestinal mucosa, SARS-CoV-2 can induce intrinsic and innate immune responses in the host involving increased cytokine release, tissue damage, and high neurosusceptibility to COVID-19, especially in the hypoxic conditions caused by lung injury. In some immune-compromised individuals, the virus may invade the brain through multiple routes, such as the vasculature and peripheral nerves. Therefore, in addition to drug treatments, such as pharmaceuticals and traditional Chinese medicine, non-pharmaceutical precautions, including facemasks and hand hygiene, are critically important.