Risk factors for diaphragmatic injury in subxiphoid video-assisted thoracoscopic surgery.

BACKGROUND: Subxiphoid video-assisted thoracoscopic surgery (VATS) is considered a safe and feasible operation for anterior mediastinal mass resection. However, diaphragmatic injury, presented as tearing or puncturing, may occur during subxiphoid VATS despite of low incidence. This study aims to explore risk factors for diaphragmatic injury in subxiphoid VATS, as well as strategies to reduce occurrence of the injury. METHODS: We retrospectively reviewed clinical records of 44 consecutive adult patients who underwent subxiphoid VATS. These patients were divided into two groups: diaphragmatic injury group and non-injury group. Perioperative outcomes and anatomic features derived from 3D CT reconstructions were compared between the two groups. RESULTS: Significant differences were observed in operation time (223.25 ± 92.57 vs. 136.28 ± 53.05, P = 0.006), xiphoid length (6.47 ± 0.85 vs. 4.79 ± 1.04, P = 0.001) and length of the xiphoid below the attachment point on the diaphragm (24.86 ± 12.02 vs. 14.61 ± 9.25, P = 0.029). Odds ratio for the length of the xiphoid below the attachment point on the diaphragm was 1.09 (1.001-1.186), P = 0.048 by binary logistic regression analysis. CONCLUSIONS: We identified the length of the xiphoid below the attachment point on the diaphragm as an independent risk factor for diaphragm injury during subxiphoid VATS. Prior to subxiphoid VATS, a 3D chest CT reconstruction is recommended to assess the patients' anatomic variations within the xiphoid process. For patients with longer xiphoid process, a higher incision at the middle and upper part of the xiphoid process, and partial xiphoid process resection or xiphoidectomy is preferred.

Delivering synaptic protein mRNAs via extracellular vesicles ameliorates cognitive impairment in a mouse model of Alzheimer's disease.

BACKGROUND: Synaptic dysfunction with reduced synaptic protein levels is a core feature of Alzheimer's disease (AD). Synaptic proteins play a central role in memory processing, learning, and AD pathogenesis. Evidence suggests that synaptic proteins in plasma neuronal-derived extracellular vesicles (EVs) are reduced in patients with AD. However, it remains unclear whether levels of synaptic proteins in EVs are associated with hippocampal atrophy of AD and whether upregulating the expression of these synaptic proteins has a beneficial effect on AD. METHODS: In this study, we included 57 patients with AD and 56 healthy controls. We evaluated their brain atrophy through magnetic resonance imaging using the medial temporal lobe atrophy score. We measured the levels of four synaptic proteins, including synaptosome-associated protein 25 (SNAP25), growth-associated protein 43 (GAP43), neurogranin, and synaptotagmin 1 in both plasma neuronal-derived EVs and cerebrospinal fluid (CSF). We further examined the association of synaptic protein levels with brain atrophy. We also evaluated the levels of these synaptic proteins in the brains of 5×FAD mice. Then, we loaded rabies virus glycoprotein-engineered EVs with messenger RNAs (mRNAs) encoding GAP43 and SNAP25 and administered these EVs to 5×FAD mice. After treatment, synaptic proteins, dendritic density, and cognitive function were evaluated. RESULTS: The results showed that GAP43, SNAP25, neurogranin, and synaptotagmin 1 were decreased in neuronal-derived EVs but increased in CSF in patients with AD, and the changes corresponded to the severity of brain atrophy. GAP43 and SNAP25 were decreased in the brains of 5×FAD mice. The engineered EVs efficiently and stably delivered these synaptic proteins to the brain, where synaptic protein levels were markedly upregulated. Upregulation of synaptic protein expression could ameliorate cognitive impairment in AD by promoting dendritic density. This marks the first successful delivery of synaptic protein mRNAs via EVs in AD mice, yielding remarkable therapeutic effects. CONCLUSIONS: Synaptic proteins are closely related to AD processes. Delivery of synaptic protein mRNAs via EVs stands as a promising effective precision treatment strategy for AD, which significantly advances the current understanding of therapeutic approaches for the disease.

Start codon-associated ribosomal frameshifting mediates nutrient stress adaptation.

A translating ribosome is typically thought to follow the reading frame defined by the selected start codon. Using super-resolution ribosome profiling, here we report pervasive out-of-frame translation immediately from the start codon. Start codon-associated ribosomal frameshifting (SCARF) stems from the slippage of ribosomes during the transition from initiation to elongation. Using a massively paralleled reporter assay, we uncovered sequence elements acting as SCARF enhancers or repressors, implying that start codon recognition is coupled with reading frame fidelity. This finding explains thousands of mass spectrometry spectra that are unannotated in the human proteome. Mechanistically, we find that the eukaryotic initiation factor 5B (eIF5B) maintains the reading frame fidelity by stabilizing initiating ribosomes. Intriguingly, amino acid starvation induces SCARF by proteasomal degradation of eIF5B. The stress-induced SCARF protects cells from starvation by enabling amino acid recycling and selective mRNA translation. Our findings illustrate a beneficial effect of translational 'noise' in nutrient stress adaptation.

Plasma biomarkers predict Alzheimer's disease before clinical onset in Chinese cohorts.

Plasma amyloid-ß (Aß)42, phosphorylated tau (p-tau)181, and neurofilament light chain (NfL) are promising biomarkers of Alzheimer's disease (AD). However, whether these biomarkers can predict AD in Chinese populations is yet to be fully explored. We therefore tested the performance of these plasma biomarkers in 126 participants with preclinical AD and 123 controls with 8-10 years of follow-up from the China Cognition and Aging Study. Plasma Aß42, p-tau181, and NfL were significantly correlated with cerebrospinal fluid counterparts and significantly altered in participants with preclinical AD. Combining plasma Aß42, p-tau181, and NfL successfully discriminated preclinical AD from controls. These findings were validated in a replication cohort including 51 familial AD mutation carriers and 52 non-carriers from the Chinese Familial Alzheimer's Disease Network. Here we show that plasma Aß42, p-tau181, and NfL may be useful for predicting AD 8 years before clinical onset in Chinese populations.

Aberrant palmitoylation caused by a ZDHHC21 mutation contributes to pathophysiology of Alzheimer's disease.

BACKGROUND: The identification of pathogenic mutations in Alzheimer's disease (AD) causal genes led to a better understanding of the pathobiology of AD. Familial Alzheimer's disease (FAD) is known to be associated with mutations in the APP, PSEN1, and PSEN2 genes involved in Aß production; however, these genetic defects occur in only about 10-20% of FAD cases, and more genes and new mechanism causing FAD remain largely obscure. METHODS: We performed exome sequencing on family members with a FAD pedigree and identified gene variant ZDHHC21 p.T209S. A ZDHHC21T209S/T209S knock-in mouse model was then generated using CRISPR/Cas9. The Morris water navigation task was then used to examine spatial learning and memory. The involvement of aberrant palmitoylation of FYN tyrosine kinase and APP in AD pathology was evaluated using biochemical methods and immunostaining. Aß and tau pathophysiology was evaluated using ELISA, biochemical methods, and immunostaining. Field recordings of synaptic long-term potentiation were obtained to examine synaptic plasticity. The density of synapses and dendritic branches was quantified using electron microscopy and Golgi staining. RESULTS: We identified a variant (c.999A > T, p.T209S) of ZDHHC21 gene in a Han Chinese family. The proband presented marked cognitive impairment at 55 years of age (Mini-Mental State Examination score = 5, Clinical Dementia Rating = 3). Considerable Aß retention was observed in the bilateral frontal, parietal, and lateral temporal cortices. The novel heterozygous missense mutation (p.T209S) was detected in all family members with AD and was not present in those unaffected, indicating cosegregation. ZDHHC21T209S/T209S mice exhibited cognitive impairment and synaptic dysfunction, suggesting the strong pathogenicity of the mutation. The ZDHHC21 p.T209S mutation significantly enhanced FYN palmitoylation, causing overactivation of NMDAR2B, inducing increased neuronal sensitivity to excitotoxicity leading to further synaptic dysfunction and neuronal loss. The palmitoylation of APP was also increased in ZDHHC21T209S/T209S mice, possibly contributing to Aß production. Palmitoyltransferase inhibitors reversed synaptic function impairment. CONCLUSIONS: ZDHHC21 p.T209S is a novel, candidate causal gene mutation in a Chinese FAD pedigree. Our discoveries strongly suggest that aberrant protein palmitoylation mediated by ZDHHC21 mutations is a new pathogenic mechanism of AD, warranting further investigations for the development of therapeutic interventions.

Akkermansia muciniphila inhibits nonalcoholic steatohepatitis by orchestrating TLR2-activated γδT17 cell and macrophage polarization.

Current evidence indicates that the next-generation probiotic Akkermansia muciniphila (A. muciniphila) has therapeutic potential for nonalcoholic fatty liver disease (NAFLD), especially its inflammatory stage known as nonalcoholic steatohepatitis (NASH). However, the mechanisms of A. muciniphila in NASH prevention remain unknown. Here, A. muciniphila supplementation prevented hepatic inflammation in high-fat diet-induced NASH mice, characterized by reduced hepatic proinflammatory macrophages (M1) and γδT and γδT17 cells. Consistently, hepatic M1 and γδT cells were enriched in biopsy-proven NASH patients and high-fat/high-carbohydrate diet-induced NASH mice. Antibiotics reduced hepatic M1, γδT and γδT17 cells in NASH mice. Furthermore, A. muciniphila inhibited intestinal barrier disruption and accordingly downregulated hepatic Toll-like receptor 2 (TLR2) expression in NASH mice. The activation of TLR2 by lipoteichoic acid enriched hepatic γδT17 cells (not M1) in normal diet-fed mice and neutralized the γδT cell-lowering and liver inflammation-protecting effects of A. muciniphila in NASH mice. Additionally, activated γδT cells could promote macrophage polarization via IL-17. Our study first supported that A. muciniphila prevented NASH by modulating TLR2-activated γδT17 cells and further macrophage polarization, facilitating clinical therapeutic applications.

DRMY1 promotes robust morphogenesis by sustaining translation of a hormone signaling protein.

Robustness is the invariant development of phenotype despite environmental changes and genetic perturbations. In the Arabidopsis flower bud, four sepals initiate at robust positions and times and grow to equal size to enclose and protect the inner floral organs. We previously characterized the mutant development related myb-like1 (drmy1), where 3-5 sepals initiate at irregular positions and variable times and grow to different sizes, compromising their protective function. The molecular mechanism underlying this loss of robustness was unclear. Here, we show that drmy1 has reduced TARGET OF RAPAMYCIN (TOR) activity, ribosomal content, and translation. Translation reduction decreases the protein level of ARABIDOPSIS RESPONSE REGULATOR7 (ARR7), a rapidly synthesized and degraded cytokinin signaling inhibitor. The resultant upregulation of cytokinin signaling disrupts the robust positioning of auxin signaling, causing variable sepal initiation. Our work shows that the homeostasis of translation, a ubiquitous cellular process, is crucial for the robust spatiotemporal patterning of organogenesis.

Shared and unique effects of ApoEε4 and pathogenic gene mutation on cognition and imaging in preclinical familial Alzheimer's disease.

BACKGROUND: Neuropsychology and imaging changes have been reported in the preclinical stage of familial Alzheimer's disease (FAD). This study investigated the effects of APOEε4 and known pathogenic gene mutation on different cognitive domains and circuit imaging markers in preclinical FAD. METHODS: One hundred thirty-nine asymptomatic subjects in FAD families, including 26 APOEε4 carriers, 17 APP and 20 PS1 mutation carriers, and 76 control subjects, went through a series of neuropsychological tests and MRI scanning. Test scores and imaging measures including volumes, diffusion indices, and functional connectivity (FC) of frontostriatal and hippocampus to posterior cingulate cortex pathways were compared between groups and analyzed for correlation. RESULTS: Compared with controls, the APOEε4 group showed increased hippocampal volume and decreased FC of fronto-caudate pathway. The APP group showed increased recall scores in auditory verbal learning test, decreased fiber number, and increased radial diffusivity and FC of frontostriatal pathway. All three genetic groups showed decreased fractional anisotropy of hippocampus to posterior cingulate cortex pathway. These neuropsychological and imaging measures were able to discriminate genetic groups from controls, with areas under the curve from 0.733 to 0.837. Circuit imaging measures are differentially associated with scores in various cognitive scales in control and genetic groups. CONCLUSIONS: There are neuropsychological and imaging changes in the preclinical stage of FAD, some of which are shared by APOEε4 and known pathogenic gene mutation, while some are unique to different genetic groups. These findings are helpful for the early identification of Alzheimer's disease and for developing generalized and individualized prevention and intervention strategies.

Start codon-associated ribosomal frameshifting mediates nutrient stress adaptation.

A translating ribosome is typically thought to follow the reading frame defined by the selected start codon. Using super-resolution ribosome profiling, here we report pervasive out-of-frame translation immediately from the start codon. The start codon-associated ribosome frameshifting (SCARF) stems from the slippage of ribosomes during the transition from initiation to elongation. Using a massively paralleled reporter assay, we uncovered sequence elements acting as SCARF enhancers or repressors, implying that start codon recognition is coupled with reading frame fidelity. This finding explains thousands of mass spectrometry spectra unannotated from human proteome. Mechanistically, we find that the eukaryotic initiation factor 5B (eIF5B) maintains the reading frame fidelity by stabilizing initiating ribosomes. Intriguingly, amino acid starvation induces SCARF by proteasomal degradation of eIF5B. The stress-induced SCARF protects cells from starvation by enabling amino acid recycling and selective mRNA translation. Our findings illustrate a beneficial effect of translational "noise" in nutrient stress adaptation.

Development and validation of a 13-gene signature associated with immune function for the detection of Alzheimer's disease.

Current knowledge of Alzheimer's disease (AD) etiology and effective therapy remains limited. Thus, the identification of biomarkers is crucial to improve the detection and treatment of patients with AD. Using robust rank aggregation method to analyze the microarray data from Gene Expression Omnibus database, we identified 1138 differentially expressed genes in AD. We then explored 13 hub genes by weighted gene co-expression network analysis, least absolute shrinkage, and selection operator, and logistic regression in the training dataset. The detection model, which composed of CD163, CDC42SE1, CECR6, CSF1R, CYP27A1, EIF4E3, H2AFJ, IFIT2, IL10RA, KIAA1324, PSTPIP1, SLA, and TBC1D2 genes, along with APOE gene, showed that the area under the curve for detecting AD was 0.821 (95% confidence interval [CI] = 0.782-0.861) and the model was validated in ADNI dataset (area under the curve = 0.776; 95%CI = 0.686-0.865). Notably, the 13 genes in the model were highly enriched in immune function. These findings have implications for the detection and therapeutic target of AD.

A blood mRNA panel that differentiates Alzheimer's disease from other dementia types.

BACKGROUND: Messenger RNAs (mRNAs) have been reported to be associated with Alzheimer's disease (AD). In this study, we investigated whether plasma-based mRNAs could distinguish AD from cognitively normal controls and other types of dementia, including vascular dementia (VaD), Parkinson's disease dementia (PDD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy body (DLB). METHODS: Plasma mRNA expression was measured in three independent datasets. Dataset 1 (n = 40; controls, 20; AD, 20) was used to identify the differentially expressed mRNAs. Dataset 2 (n = 122; controls: 60; AD: 62) was used to develop a diagnostic AD model using an mRNA panel. Furthermore, we applied the model to Dataset 3 (n = 334; control, 57; AD, 58; VaD, 55; PDD, 54; bvFTD, 55; DLB, 55) to verify its ability to identify AD and other types of dementia. RESULTS: Dataset 1 showed 22 upregulated and 21 downregulated mRNAs. A panel of six mRNAs distinguished AD from the control group in Dataset 2. The panel was used to successfully differentiate AD from other types of dementia in Dataset 3. CONCLUSIONS: An AD-specific panel of six mRNAs was created that can be used for AD diagnosis.

A 19-Year-Old Adolescent with Probable Alzheimer's Disease.

Alzheimer's disease (AD) primarily affects older adults. In this report, we present the case of a 19-year-old male with gradual memory decline for 2 years and World Health Organization-University of California Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT) results also showing memory impairment. Positron emission tomography-magnetic resonance imaging with 18F fluorodeoxyglucose revealed atrophy of the bilateral hippocampus and hypometabolism in the bilateral temporal lobe. Examination of the patient's cerebrospinal fluid showed an increased concentration of p-tau181 and a decreased amyloid-ß 42/40 ratio. However, through whole-genome sequencing, no known gene mutations were identified. Considering the above, the patient was diagnosed with probable AD.

A Group of Long Non-coding RNAs in Blood Acts as a Specific Biomarker of Alzheimer's Disease.

Long non-coding RNAs (lncRNAs) have been identified to be involved in the pathogenesis of Alzheimer's disease (AD). In this study, we evaluated whether lncRNAs can be used to discriminate AD patients from controls and patients with other dementias, such as vascular, Parkinson's disease, behavioral variant frontotemporal, and dementia with Lewy body. In this study, we used three datasets to measure the blood lncRNA levels. A pilot study (dataset 1, n = 40; controls, 20; AD, 20) was used to screen for differentially expressed lncRNAs. Dataset 2 (n = 174; controls, 86; AD, 88) was used to identify a lncRNA panel for the diagnostic model. Dataset 3 (n = 333; control, 60; AD, 54; vascular dementia, 53; Parkinson's disease dementia, 55; behavioral variant frontotemporal dementia, 56; and dementia with Lewy body, 55) was used to validate the diagnostic model. In dataset 1, 12 upregulated and 15 downregulated lncRNAs were identified. In dataset 2, a panel of seven lncRNAs was found to have the ability to differentiate AD patients from controls. Finally, this panel was applied to dataset 3 to successfully distinguish AD from other dementias. This study proposes a panel of seven lncRNAs as specific and promising biomarker for AD diagnosis.

Proteomic profiling of circulating plasma exosomes reveals novel biomarkers of Alzheimer's disease.

BACKGROUND: Neuronal- and astrocyte-derived exosomes have been identified as an optimal source for screening biomarkers for Alzheimer's disease (AD). However, few studies focus on the bulk exosome population isolated from plasma of AD. This study investigated whether proteins in bulk exosomes can aid in the diagnosis of AD. METHODS: The plasma exosomes were collected by ultracentrifuge. Protein samples were extracted from exosomes. Cerebrospinal fluid levels of amyloid ß (Aß)42 and phosphorylated tau (P-tau)181 were measured for diagnostic purposes. A pilot study (controls, 20; AD, 20) followed by a second dataset (controls, 56; AD, 58) was used to establish a diagnostic model of AD. Mass spectrometry-based proteomics was performed to profile the plasma exosomal proteome. Parallel reaction monitoring was used to further confirm the differentially expressed proteins. RESULTS: In total, 328 proteins in plasma exosomes were quantified. Among them, 31 proteins were altered in AD patients, and 12 were validated. The receiver operating characteristic curve analysis revealed a combination of six proteins (upregulated: Ig-like domain-containing protein (A0A0G2JRQ6), complement C1q subcomponent subunit C (C1QC), complement component C9 (CO9), platelet glycoprotein Ib beta chain (GP1BB), Ras suppressor protein 1 (RSU1); downregulated: disintegrin and metalloproteinase domain 10 (ADA10)) has the capacity to differentiate AD patients from healthy controls with high accuracy. Linear correlation analysis showed that the combination was significantly correlated with cognitive performance. CONCLUSIONS: The combination of plasma exosomal proteins A0A0G2JRQ6, C1QC, CO9, GP1BB, RSU1, and ADA10 acts as a novel candidate biomarker to differentiate AD patients from healthy individuals.

A circular RNA blood panel that differentiates Alzheimer's disease from other dementia types.

BACKGROUND: Circular RNAs (circRNAs) have been demonstrated to be associated with Alzheimer's disease (AD). Here, we conducted a study to explore whether circRNAs have the ability to differentiate AD from cognitively normal controls and other types of dementia, such as vascular dementia (VaD), Parkinson's disease dementia (PDD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy body (DLB). METHODS: Three datasets were included in this study to measure blood circRNAs. The pilot study (Dataset 1, n = 40; controls, 20; AD, 20) was used to screen differentially expressed circRNAs. Dataset 2 (n = 124; controls, 61; AD, 63) was recruited for the establishment of the diagnostic model using a circRNA panel. Further, the Dataset 3 (n = 321; control, 58; AD, 60; VaD, 50; PDD, 51; bvFTD, 52; DLB, 50) was used to verify the diagnostic model. RESULTS: In Dataset 1, 22 upregulated and 19 downregulated circRNAs were revealed. In Dataset 2, a six-circRNA panel was found to be able to distinguish patients with AD from controls. Then this panel was applied to Dataset 3 and successfully differentiated AD from other types of dementia. CONCLUSION: This study suggested that a six-circRNA panel is AD-specific and a promising biomarker of AD.

Clinical Practice Guidelines for the Management of Behavioral and Psychological Symptoms of Dementia: A Systematic Review With AGREE II.

Background: High-quality clinical practice guidelines (CPGs) are important for the effective treatment of behavioral and psychological symptoms of dementia (BPSD). However, recommendations provided by different quality guidelines may lead to varied clinical practice outcomes. Objective: To assess the quality of available CPGs for the management of BPSD and summarize the best recommendations for treating BPSD. Methods: This was a systematic review of CPGs for the management of BPSD with data obtained from electronic databases and evaluated using the Appraisal of Guidelines for Research and Evaluation II instrument, consisting of six domains: "Scope and purpose", "Stakeholder involvement", "Rigor of development", "Clarity of presentation", "Applicability", and "Editorial independence". The criteria for high-quality guidelines were set as: the score of high-quality guidelines in the "Rigor of development" domain should be ≥60% and as well as a score of >60% in at least three other domains. High-quality guidelines were selected for recommendation extraction, and the final recommendations were formed in combination with the latest meta-analysis and randomized clinical-trial results. Results: In term of median scores in each domain for the six included CPGs, "Scope and purpose" (87.5%) scored better than all others, whereas "Applicability" (46.5%) was the domain with the lowest score. Four CPGs (2015 APA, 2018 NICE, 2018 CANADA, 2020 EAN) met the criteria of high-quality guidelines and were used to extract recommendations. From these four CPGs, nine specific recommendations related to the management of BPSD were summarized, of which seven were related to pharmacological treatment and two to non-pharmacological treatment. These recommendations covered the applicability of antipsychotic drugs, medication recommendations, withdrawal times, and several suitable non-pharmacological therapies. Conclusion: The quality of CPGs for the management of BPSD requires improvement, especially for the "Applicability" domain. For psychotic-like symptoms in dementia, the use of antipsychotics should be based on the individual's risk-benefit ratio, and the use of atypical antipsychotics seems to be a better choice. Non-pharmacological treatments may be suitable for emotional symptoms and sleep disorders. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020209204.

Phosphorylated Tau 181 Serum Levels Predict Alzheimer's Disease in the Preclinical Stage.

Background: There is an urgent need for cost-effective, easy-to-measure biomarkers to identify subjects who will develop Alzheimer's disease (AD), especially at the pre-symptomatic stage. This stage can be determined in autosomal dominant AD (ADAD) which offers the opportunity to observe the dynamic biomarker changes during the life-course of AD stages. This study aimed to investigate serum biomarkers during different AD stages and potential novel protein biomarkers of presymptomatic AD. Methods: In the first stage, 32 individuals [20 mutation carriers including 10 with AD, and 10 with mild cognitive impairment (MCI), and 12 healthy controls] from ADAD families were analyzed. All subjects underwent a complete clinical evaluation and a comprehensive neuropsychological battery. Serum samples were collected from all subjects, and antibody arrays were used to analyze 170 proteins in these samples. The most promising biomarkers were identified during this screening and were then measured in serum samples of 12 subjects with pre-MCI and 20 controls. Results: The serum levels of 13 proteins were significantly different in patients with AD or MCI compared to controls. Of the 13 proteins, cathepsin D, immunoglobulin E, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9 (MMP-9), von Willebrand factor (vWF), haptoglobin, and phosphorylated Tau-181 (p-Tau181) correlated with all cognitive measures (R2 = -0.69-0.76). The areas under the receiver operating characteristic curve of these seven proteins were 0.71-0.93 for the classification of AD and 0.57-0.95 for the classification of MCI. Higher levels of p-Tau181 were found in the serum of pre-MCI subjects than in the serum of controls. The p-Tau181 serum level might detect AD before symptoms occur (area under the curve 0.85, sensitivity 75%, specificity 81.67%). Conclusions: A total of 13 serum proteins showed significant differences between subjects with AD and MCI and healthy controls. The p-Tau181 serum level might be a broadly available and cost-effective biomarker to identify individuals with preclinical AD and assess the severity of AD.

Elucidating the anatomy of the quadrivial pattern of the right upper lobe bronchus using 3D-CT images.

Background: A preoperative understanding of the thoracic anatomy of the patients with the quadrivial pattern of branching of the right upper lobe is key to successful surgery. We analyzed the quadrivial pattern of division of the right upper lobe bronchus of patients using three-dimensional (3D) computed tomography (CT) angiography and bronchography. Methods: A total of 212 consecutive adult patients who had undergone thoracic CT scans before surgery at the Zhujiang Hospital of the Southern Medical University from August 2020 to August 2021 was used for retrospective study. The 3D-CT images were taken using Mimics software. Radiology technicians processed all the 3D images, and thoracic surgeons confirmed the validity of all the reconstructions. Results: Six (2.83%) were identified as having a quadrivial pattern of division of the right upper lobe bronchus with 1 female, and 5 males. Based on the number of pulmonary artery branches, 5 (83.3%) and 1 (16.7%) were classified as "trunk superior (Tr.sup) + ascending artery (A.asc) and Tr.sup + trunk inferior (Tr.inf) + ascending artery (A.asc) (1/6, 16.7%). Based on the number of ascending artery branches, the patients were also divided into type A (3/6, 50%) and type B (3/6, 50%). The patients were also divided into 1 of the following three types based on the origins of the A2: (I) A2 originates from A6 (1/6, 16.7%); (II) A2 originates from the pulmonary trunk (4/6, 66.7%); and (III) A2a originates from A3, and A2b originates from the pulmonary artery stem (1/6, 16.7%). According to the number of A1b branches, patients were divided into two types: (I) 1 branch (4/6, 66.7 %); and (II) 2 branches (2/6, 33.3 %). In the present study, anterior + central type was observed which classified into two types: (I) type Iab, the anterior vein ran from V1a to V1b (4/6, 66.7%); and (II) type Ib, the anterior vein ran from V1b only (2/6, 33.3%). Conclusions: 3D-CT was successfully used for analyzing the quadrivial bronchovascular patterns of the right upper lobe bronchus. Our study provides certain references to perform anatomical pulmonary segmentectomy, which should improve the success rate of operations.