Choline metabolism reprogramming mediates an immunosuppressive microenvironment in non-small cell lung cancer (NSCLC) by promoting tumor-associated macrophage functional polarization and endothelial cell proliferation.

INTRODUCTION: Lung cancer is a prevalent malignancy globally, and immunotherapy has revolutionized its treatment. However, resistance to immunotherapy remains a challenge. Abnormal cholinesterase (ChE) activity and choline metabolism are associated with tumor oncogenesis, progression, and poor prognosis in multiple cancers. Yet, the precise mechanism underlying the relationship between ChE, choline metabolism and tumor immune microenvironment in lung cancer, and the response and resistance of immunotherapy still unclear. METHODS: Firstly, 277 advanced non-small cell lung cancer (NSCLC) patients receiving first-line immunotherapy in Sun Yat-sen University Cancer Center were enrolled in the study. Pretreatment and the alteration of ChE after 2 courses of immunotherapy and survival outcomes were collected. Kaplan-Meier survival and cox regression analysis were performed, and nomogram was conducted to identify the prognostic and predicted values. Secondly, choline metabolism-related genes were screened using Cox regression, and a prognostic model was constructed. Functional enrichment analysis and immune microenvironment analysis were also conducted. Lastly, to gain further insights into potential mechanisms, single-cell analysis was performed. RESULTS: Firstly, baseline high level ChE and the elevation of ChE after immunotherapy were significantly associated with better survival outcomes for advanced NSCLC. Constructed nomogram based on the significant variables from the multivariate Cox analysis performed well in discrimination and calibration. Secondly, 4 choline metabolism-related genes (MTHFD1, PDGFB, PIK3R3, CHKB) were screened and developed a risk signature that was found to be related to a poorer prognosis. Further analysis revealed that the choline metabolism-related genes signature was associated with immunosuppressive tumor microenvironment, immune escape and metabolic reprogramming. scRNA-seq showed that MTHFD1 was specifically distributed in tumor-associated macrophages (TAMs), mediating the differentiation and immunosuppressive functions of macrophages, which may potentially impact endothelial cell proliferation and tumor angiogenesis. CONCLUSION: Our study highlights the discovery of ChE as a prognostic marker in advanced NSCLC, suggesting its potential for identifying patients who may benefit from immunotherapy. Additionally, we developed a prognostic signature based on choline metabolism-related genes, revealing the correlation with the immunosuppressive microenvironment and uncovering the role of MTHFD1 in macrophage differentiation and endothelial cell proliferation, providing insights into the intricate workings of choline metabolism in NSCLC pathogenesis.

Cdc42-driven endosomal cholesterol transport promotes collateral resistance in HER2-positive gastric cancer.

Resistance to trastuzumab and the poor efficacy of subsequent chemotherapy have become major challenges for HER2-positive gastric cancer (GC). As resistance evolves, tumor cells may acquire a new drug susceptibility profile, profoundly impacting the subsequent treatment selection and patient survival. However, the interplay between trastuzumab and other types of drugs in HER2-positive GC remains elusive. In our study, we utilized resistant cell lines and tissue specimens to map the drug susceptibility profile of trastuzumab-resistant GC, discovering that resistance to trastuzumab induces collateral resistance to commonly used chemotherapeutic agents. Additionally, patients with collateral resistance distinguished by a 13-gene scoring model in HER2-positive GC cohorts are predicted to have a poor prognosis and may be sensitive to cholesterol-lowering drugs. Mechanistically, endosomal cholesterol transport is further confirmed to enrich cholesterol in the plasma membrane, contributing to collateral resistance through the Hedgehog-ABCB1 axis. As a driver for cholesterol, Cdc42 is activated by the formation of the NPC1-TßRI-Cdc42 complex to facilitate endosomal cholesterol transport. We demonstrated that inhibiting Cdc42 activation with ZCL278 reduces cholesterol levels in the plasma membrane and reverses collateral resistance between trastuzumab and chemotherapy in vitro and in vivo. Collectively, our findings verify the phenomena and mechanism of collateral resistance between trastuzumab and chemotherapy, and propose a potential therapeutic target and strategy in the second-line treatment for trastuzumab-resistant HER2-positive GC.

Screening of Candidate Effectors from Magnaporthe oryzae by In Vitro Secretomic Analysis.

Magnaporthe oryzae is the causal agent of rice blast, one of the most serious diseases of rice worldwide. Secreted proteins play essential roles during a M. oryzae-rice interaction. Although much progress has been made in recent decades, it is still necessary to systematically explore M. oryzae-secreted proteins and to analyze their functions. This study employs a shotgun-based proteomic analysis to investigate the in vitro secretome of M. oryzae by spraying fungus conidia onto the PVDF membrane to mimic the early stages of infection, during which 3315 non-redundant secreted proteins were identified. Among these proteins, 9.6% (319) and 24.7% (818) are classified as classically or non-classically secreted proteins, while the remaining 1988 proteins (60.0%) are secreted through currently unknown secretory pathway. Functional characteristics analysis show that 257 (7.8%) and 90 (2.7%) secreted proteins are annotated as CAZymes and candidate effectors, respectively. Eighteen candidate effectors are selected for further experimental validation. All 18 genes encoding candidate effectors are significantly up- or down-regulated during the early infection process. Sixteen of the eighteen candidate effectors cause the suppression of BAX-mediated cell death in Nicotiana benthamiana by using an Agrobacterium-mediated transient expression assay, suggesting their involvement in pathogenicity related to secretion effectors. Our results provide high-quality experimental secretome data of M. oryzae and will expand our knowledge on the molecular mechanisms of M. oryzae pathogenesis.

FoCupin1, a Cupin_1 domain-containing protein, is necessary for the virulence of Fusarium oxysporum f. sp. cubense tropical race 4.

Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) is an important soilborne fungal pathogen that causes the most devastating banana disease. Effectors secreted by microbes contribute to pathogen virulence on host plants in plant-microbe interactions. However, functions of Foc TR4 effectors remain largely unexplored. In this study, we characterized a novel cupin_1 domain-containing protein (FoCupin1) from Foc TR4. Sequence analysis indicated that the homologous proteins of FoCupin1 in phytopathogenic fungi were evolutionarily conserved. Furthermore, FoCupin1 could suppress BAX-mediated cell death and significantly downregulate the expression of defense-related genes in tobacco by using the Agrobacterium-mediated transient expression system. FoCupin1 was highly induced in the early stage of Foc TR4 infection. The deletion of FoCupin1 gene did not affect Foc TR4 growth and conidiation. However, FoCupin1 deletion significantly reduced Foc TR4 virulence on banana plants, which was further confirmed by biomass assay. The expression of the defense-related genes in banana was significantly induced after inoculation with FoCupin1 mutants. These results collectively indicate FoCupin1 is a putative effector protein that plays an essential role in Foc TR4 pathogenicity. These findings suggest a novel role for cupin_1 domain-containing proteins and deepen our understanding of effector-mediated Foc TR4 pathogenesis.

[Chinese Expert Consensus on Management of Special Adverse Effects 
Associated with Lorlatinib].

Anaplastic lymphoma kinase (ALK) fusions represent the second most common oncogenic driver mutation in non-small cell lung cancer (NSCLC). As the new class of 3rd generation of ALK tyrosine kinase inhibitor (TKI), lorlatinib has shown robust potency and brain-penetrant clinical activity against a wide spectrum of multiple resistance mutations within the ALK domain detected during crizotinib and 2nd generation ALK TKI treatment. Lorlatinib is generally well-tolerated with unique adverse drug reaction/adverse event, including hyperlipidemia and central nervous system effects, which are mostly mild to moderate severity and manageable through dosage modifications and/or standard medical intervention. For advanced NSCLC with ALK positivity, patients should be evaluated for baseline characteristics and pre-existing medication, informed of the potential toxicities, and periodically monitored to balance benefits and risks. Moreover, a multidisciplinary group of experts is essential to establish a comprehensive diagnostic and therapeutic strategy.
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Pharmacological induction of AMFR increases functional EAAT2 oligomer levels and reduces epileptic seizures in mice.

Dysregulation of excitatory amino acid transporter 2 (EAAT2) contributes to the development of temporal lobe epilepsy (TLE). Several strategies for increasing total EAAT2 levels have been proposed. However, the mechanism underlying the oligomeric assembly of EAAT2, impairment of which inhibits the formation of functional oligomers by EAAT2 monomers, is still poorly understood. In the present study, we identified E3 ubiquitin ligase AMFR as an EAAT2-interacting protein. AMFR specifically increased the level of EAAT2 oligomers rather than inducing protein degradation through K542-specific ubiquitination. By using tissues from humans with TLE and epilepsy model mice, we observed that AMFR and EAAT2 oligomer levels were simultaneously decreased in the hippocampus. Screening of 2386 FDA-approved drugs revealed that the most common analgesic/antipyretic medicine, acetaminophen (APAP), can induce AMFR transcriptional activation via transcription factor SP1. Administration of APAP protected against pentylenetetrazol-induced epileptogenesis. In mice with chronic epilepsy, APAP treatment partially reduced the occurrence of spontaneous seizures and greatly enhanced the antiepileptic effects of 17AAG, an Hsp90 inhibitor that upregulates total EAAT2 levels, when the 2 compounds were administered together. In summary, our studies reveal an essential role for AMFR in regulating the oligomeric state of EAAT2 and suggest that APAP can improve the efficacy of EAAT2-targeted antiepileptic treatments.

The Nasopharynx Swab Test for Coronavirus Disease-2019 Is Mild and Will Not Cause Significant Pain and Anxiety: A Cross-Sectional Study Based on Psychiatrists.

Background: Laboratory viral nucleic acid testing (NAT), such as the nasopharyngeal swab test, is now recommended as the gold standard for the diagnosis of Coronavirus disease-2019 (COVID-19). However, the nasopharyngeal swab testing process may cause some discomfort. Objective: To investigate the influence of nasopharyngeal swab tests on the anxiety and pain felt by psychiatric medical staff. Methods: A total of 174 psychiatric medical staff (namely 97 doctors, 68 nurses, and nine administrators) and 27 controls were included in the current study. A self-designed questionnaire was used to collect their general demographic information (age, gender, marriage, occupation, profession, smoking history, alcohol consumption history, tea drinking history, previous history of anxiety and depression) as well as their subjective experience, such as nausea, vomiting, coughing, worry, fear, etc, during nasopharyngeal swab collection. The Numerical Rating Scale (NRS) and the State-Trait Anxiety Inventory (STAI) were used to assess the subjects' pain and state anxiety, respectively. Results: There were no statistical differences (p>0.05) in age, marriage, smoking history, a history of anxiety and depression, pain scores, and anxiety scores between different professions and genders. The results of partial correlation analysis (controlled for gender and history of depression or anxiety) indicated that the male gender was negatively correlated with being anxious (r=-0.148, p=0.037) and nervous (r=-0.171 p=0.016), although there was no significant difference in pain and anxiety between men and women. In addition, marriage might help women resist negative emotions. Conclusions: 1) There will be mild discomfort during nucleic acid testing, but not enough to cause pain and anxiety; 2) women are more likely to be anxious and nervous during the nucleic acid testing.

Bioinformatics analysis based on immune-autophagy-related lncRNAs combined with immune infiltration in bladder cancer.

BACKGROUND: To construct a prognostic model based on immune-autophagy-related long noncoding RNA (IArlncRNAs), mainly to predict the overall survival rate (OS) of bladder cancer patients and investigate its possible mechanisms. METHODS: Transcriptome and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. We identified the IArlncRNA by co-expression analysis, differential expression analysis, and Venn analysis. Then, we identified the independent prognostic IArlncRNAs by univariate Cox regression, LASSO regression, and multivariate Cox regression analysis. Moreover, we constructed the prognostic model based on the independent prognostic IArlncRNAs and clinical features. The proportion of 22 immune cell subtypes was analyzed by the CIBERSORT algorithm. Besides, we identified the differential proportion of 22 immune cell subtypes between the high- and low-risk groups. In addition, we identified the correlation between immune-infiltrating cells (screened by univariate Cox regression and multivariate Cox regression analysis) and IArlncRNAs by Pearson correlation analysis. Finally, we estimated the half-maximal inhibitory concentration (IC50) of chemotherapeutic drugs in patients with bladder cancer based on the pRRophetic algorithm. RESULTS: Four IArlncRNAs were identified as independent prognostic factors, including AL136084.3, AC006270.1, Z84484.1, and AL513218.1. The OS of patients in the high-risk group was significantly worse compared to the low-risk group. The nomogram showed an excellent predictive effect with the C-index of 0.64. The calibration chart showed a good actual vs. predicted probability. B cells naïve, T cells CD8, T cells CD4 memory resting, T cells follicular helper, macrophages M1, dendritic resting and activated cells had higher infiltrations in the low-risk group and lower infiltration of macrophages M2. The fraction of macrophages M2 was positively associated with AL136084.3. The fraction of T cells CD8 was positively associated with Z84484.1. The fraction of M + macrophages M0 was negatively associated with Z84484.1. Further, we identified the differential IC50 of 24 chemotherapeutic drugs between the high- and low-risk groups. CONCLUSIONS: The prognostic model based on 4 IArlncRNAs showed an excellent predictive effect. Furthermore, we reasonably speculated that IArlncRNAs are directly or indirectly involved in the immune regulation of the tumor microenvironment (TME), as well as autophagy.

A Preliminary Investigation on Plasma Cell Adhesion Molecules Levels by Protein Microarray Technology in Major Depressive Disorder.

Objectives: Major depressive disorder (MDD) is a serious mental disorder, and there is a great difficulty to diagnose and treat. Hitherto, relatively few studies have explored the correlation between the levels of plasma cell adhesion molecules and MDD. Methods: Thirty outpatients with acute episodes of MDD in Shanghai Mental Health Center and 34 healthy volunteers from the community were recruited as subjects. Protein microarray technology was applied to compared the differences in plasma levels of 17 kinds of adhesion molecular proteins between the two groups. Meanwhile, the diagnostic value of different proteins in depression was discussed by using the receiver operating characteristic curve. Results: The levels of Carcinoembryonic Antigen Related Cell Adhesion Molecule-1(CEACAM-1) and Neural Cell Adhesion Molecule (NrCAM) in MDD patients were significantly higher than those in healthy controls (P < 0.05). The area under ROC curve of CEACAM-1 combined with NrCAM was 0.723, with the sensitivity 0.800 and the specificity 0.676. Conclusion: The plasma levels of CEACAM-1 and NrCAM were significantly up-regulated in MDD, and their combined application was of potential diagnostic value, deserving to expand the sample size for further verification.

Immediate psychological distress in quarantined patients with COVID-19 and its association with peripheral inflammation: A mixed-method study.

Since the end of 2019, Corona Virus Disease 2019 (COVID-19) has been the cause of a worldwide pandemic. The mental status of patients with COVID-19 who have been quarantined and the interactions between their psychological distress and physiological levels of inflammation have yet to be analyzed. Using a mixed-method triangulation design (QUAN + QUAL), this study investigated and compared the mental status and inflammatory markers of 103 patients who, while hospitalized with mild symptoms, tested positive with COVID-19 and 103 matched controls that were COVID-19 negative. The severity of depression, anxiety, and post-traumatic stress symptoms (PTSS) was measured via an on-line survey. Using a convenience sampling technique, qualitative data were collected until the point of data saturation. In addition, a semi-structured interview was conducted among five patients with COVID-19. Peripheral inflammatory markers were also collected in patients, both at baseline and within ± three days of completing the on-line survey. Results revealed that COVID-19 patients, when compared to non-COVID controls, manifested higher levels of depression (P < 0.001), anxiety (P < 0.001), and post-traumatic stress symptoms (P < 0.001). A gender effect was observed in the score of "Perceived Helplessness", the subscale of PSS-10, with female patients showing higher scores compared to male patients (Z = 2.56, P = 0.010), female (Z = 2.37, P = 0.018) and male controls (Z = 2.87, P = 0.004). Levels of CRP, a peripheral inflammatory indicator, correlated positively with the PHQ-9 total score (R = 0.37, P = 0.003, Spearman's correlation) of patients who presented symptoms of depression. Moreover, the change of CRP level from baseline inversely correlated with the PHQ-9 total score (R = -0.31, P = 0.002), indicative of improvement of depression symptoms. Qualitative analysis revealed similar results with respect to patient reports of negative feelings, including fear, guilt, and helplessness. Stigma and uncertainty of viral disease progression were two main concerns expressed by COVID-19 patients. Our results indicate that significant psychological distress was experienced by hospitalized COVID-19 patients and that levels of depressive features may be related to the inflammation markers in these patients. Thus, we recommend that necessary measures should be provided to address depression and other psychiatric symptoms for COVID-19 patients and attention should be paid to patient perceived stigma and coping strategies when delivering psychological interventions.

Lateral Subcutaneous Locking Compression Plate and Small Incision Reduction for Distal-third Diaphyseal Humerus Fractures.

OBJECTIVE: Iatrogenic radial nerve injury is a great challenge for orthopaedic surgeons who deal with distal-third diaphyseal humerus fractures. Conventional open reduction and internal fixation (ORIF) remains the gold standard, but complications such as nonunion and iatrogenic radial nerve injury still occur. We fixed the fractures with a lateral locking compression plate (LCP) subcutaneously after small incision reduction to protect the radial nerve. This study reports the clinical and radiographic outcomes of our modified method. METHODS: Thirty-eight patients with distal-third diaphyseal humerus fractures were treated with lateral subcutaneous LCP and small incision reduction at our department between September 2013 and August 2016. There were 33 males and 5 females, with an average age of 30.3 years (range, 17 to 49 years). All the cases were types A or B (AO/OTA classification, type A, 24 cases; type B, 14 cases). Among them, 6 cases were combined with preoperative radial nerve palsy. All patients were diagnosed with closed humeral fractures after X-ray examination, and had typical upper limb pain, swelling, and movement disorders. The operations were performed by a single surgeons' team. Union time, range of motion (ROM), University of California, Los Angeles (UCLA) shoulder rating scale, and Mayo Elbow Performance Index (MEPI) scores were assessed to evaluate the postoperative results. RESULTS: All patients were followed up for an average of 11.4 months (range, 3 to 36 months). The average operation time was 75.5 min (range, 60 to 150 min) and average intraoperative radiation exposure was 10.5 s (range, 8 to 18 s). Bony union was achieved in all cases after an average of 16.2 weeks (range, 12 to 25 weeks). No complications such as infection or screw and plate fracture occurred, and no iatrogenic radial nerve injury was observed. According to the UCLA shoulder rating scale, the average score was 33.7 (range, 31 to 35), with 33 excellent (86.8%) and 5 good cases (13.2%). They were all excellent according to their MEPI scores (ranging, 94 to 100, with an average of 97.4). The average operation time for secondary removal of the plate was 15.2 min (range, 10 to 20 min), and no complications such as infection or secondary radial nerve injury occurred. CONCLUSIONS: Lateral subcutaneous LCP and small incision reduction may reduce the risk of iatrogenic radial nerve injury significantly in the treatment of distal-third diaphyseal humerus fractures. It also leads to solid fixation, good postoperative function, and convenient removal of the plate without injuring the radial nerve.

Asymmetry of Hippocampus and Amygdala Defect in Subjective Cognitive Decline Among the Community Dwelling Chinese.

Background: Subjective cognitive decline (SCD) may be the first clinical sign of Alzheimer's disease (AD). SCD individuals with normal cognition may already have significant medial temporal lobe atrophy. However, few studies have been devoted to exploring the alteration of left-right asymmetry with hippocampus and amygdala in SCD. The aim of this study was to compare SCD individuals with amnestic mild cognitive impairment (MCI) patients and the normal population for volume and asymmetry of hippocampus, amygdala and temporal horn, and to assess their relationship with cognitive function in elderly population living in China. Methods: 111 SCD, 30 MCI, and 67 healthy controls (HC) underwent a standard T1-weighted MRI, from which the volumes of the hippocampus and amygdala were calculated and compared. Then we evaluated the pattern and extent of asymmetry in hippocampus and amygdala of these samples. Furthermore, we also investigated the relationship between the altered brain regions and cognitive function. Results: Among the three groups, SCD showed more depressive symptoms (p < 0.001) and higher percentage of heart disease (16.4% vs. 35.1%, p = 0.007) than controls. In terms of brain data, significant differences were found in the volume and asymmetry of both hippocampus and amygdala among the three groups (P < 0.05). In logistic analysis controlled by age, gender, education level, depression symptoms, anxiety symptom, somatic disease and lifestyle in terms of smoking, both SCD and MCI individuals showed significant decreased right hippocampal and amygdala volume than controls. For asymmetry pattern, a ladder-shaped difference of left-larger-than-right asymmetry was found in amygdala with MCI>SCD>HC, and an opposite asymmetry of left-less-than-right pattern was found with HC>SCD>MCI in hippocampus. Furthermore, correlation was shown between the volume of right hippocampus and right amygdala with MMSE and MoCA in SCD group. Conclusion: Our results supported that SCD individuals are biologically distinguishable from HC, and this may relate to cognitive impairment, although more longitudinal studies are need to investigate this further.Moreover, different levels of asymmetry in hippocampus and amygdala might be a potential dividing factor to differentiate clinical diagnosis.

Caregivers' attitude toward disclosure of Alzheimer's disease diagnosis in Urban China.

BACKGROUND: Disclosing the diagnosis of Alzheimer's disease (AD) to a patient is controversial. There is significant stigma associated with a diagnosis of AD or dementia in China, but the attitude of the society toward disclosure of such a diagnosis had not been formally evaluated prior to our study. Therefore, we aimed to evaluate the attitude toward disclosing an AD diagnosis to patients in China with cognitive impairment from their caregivers, and the factors that may affect their attitude. METHODS: We designed a 17-item questionnaire and administered this questionnaire to caregivers, who accompanied patients with cognitive impairment or dementia in three major hospitals in Shanghai, China. The caregiver's attitude toward disclosing the diagnosis of AD as evaluated by the questionnaire was compared to that of disclosing the diagnosis of terminal cancer. RESULTS: A majority (95.7%) of the 175 interviewed participants (mean 14.2 years of education received) wished to know their own diagnosis if they were diagnosed with AD, and 97.6% preferred the doctor to tell their family members if they were diagnosed with AD. If a family member of the participants suffered from AD, 82.9% preferred to have the diagnosis disclosed to the patient. "Cognitive impairment" was the most accepted term by caregivers to disclose AD diagnosis in Chinese. CONCLUSION: This study suggests most of the well-educated individuals in a Chinese urban area favored disclosing the diagnosis when they or their family members were diagnosed with AD.

Application of remifentanil for conscious sedation and analgesia in short-term ERCP and EST surgery.

This study aims to observe and evaluate the use of remifentanil in conscious sedation and analgesia for the safety and comfort of patients undergoing short-term endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST).Sixty-eight patients who underwent ERCP and EST were randomly divided into two groups: research group and control group. Patients in the research group were intravenously injected with remifentanil (80-2/3* age) for 1 to 2 minutes, combined with the intravenous injection of propofol (20-30 mg) during the course of treatment. ERCP surgery was performed when Ramsay sedation scale (RSS) score reached 2-3. During the surgery, patients were closely monitored for cough symptoms, aspiration, and respiratory and circulatory system performance, and timely treatment was performed. Sedative drugs were not given in patients in the control group.In research group, the circulatory and respiratory depression of patients was mild, only one patient needed to be treated, and there was no arrhythmia requiring treatment. Five patients had respiratory depression (blood oxygen saturation decreased to <90%), which was immediately corrected. There were no interruptions during surgery due to body movement, cough, or aspiration.The use of remifentanil for conscious sedation and analgesia can be broadly applied in short-term ERCP, which greatly improves patient comfort during the surgery. This approach may bear promise for a widespread use in future clinical practice.

Prevalence, Incidence, Risk and Protective Factors of Amnestic Mild Cognitive Impairment in the Elderly in Shanghai.

BACKGROUND: Amnestic MCI (aMCI) has notably increased in Shanghai, China. OBJECTIVE: The study was designed to estimate the prevalence and incidence rates of aMCI and to determine the risk and protective factors for aMCI among persons ≥ 60 years-old and ≥ 70 years-old in Shanghai communities, respectively. METHOD: We carried out this 1-year longitudinal study to survey a random sample of 1,302 individuals ≥ 60 years-old, to collect baseline and follow-up data about lifestyle through self-reports, and vascular and comorbid conditions from medical records and a physical examination. We also analyzed a subgroup of individuals ≥ 70 years-old. RESULTS: The prevalence rate of aMCI in persons ≥ 60 years-old was 22.3%, and the incidence rate (per 1,000 person-years) was 96.9. Being female was a risk factor for aMCI; protective factors included smoking, drinking tea, engaging in intellectual work before retirement, social activities and hobbies, regular reading habits, and surfing the internet. The prevalence rate of aMCI in persons ≥ 70 years was 30.3%, and the incidence rate was 145.6. Smoking, drinking tea, and surfing the internet were not protective factors for this age group (≥ 70 years). CONCLUSION: The present study indicates that aMCI is a considerable health problem in Shanghai. Preventive strategies for aMCI are needed to enhance lifestyle factors that promote brain activity.

The efficacy of plasma biomarkers in early diagnosis of Alzheimer's disease.

BACKGROUND: Early diagnosis of Alzheimer's disease (AD) is imperative for the prevention of disease progression and the development of effective treatments. OBJECTIVE: Clinically, AD diagnosis has been based on adherence to clinical criteria. It has recently been proposed that diagnostic criteria should also incorporate biomarker findings. However, the most studied candidates or group of candidates for AD biomarkers, including pathological processes and proteins, needs further research. The current study aimed to investigate the capabilities of the following plasma proteins in the diagnosis of AD and amnesia mild cognitive impairment (aMCI): peripheral interleukin (IL) 10, IL-6, amyloid-ß (Aß) 40, Aß42, phosphorylated tau 181, and total tau. METHODS: In addition to 122 normal control (NC) group, 97 AD patients and 54 aMCI patients were recruited for this study. An enzyme-linked immunosorbent assay was used to analyze the concentration of the following blood plasma biomarkers: IL-10, IL-6, Aß40, Aß42, phosphorylated tau 181, and total tau. RESULTS: A one-way analysis of variance (one-factor analysis of variance) of Aß40 and IL-10 levels revealed a statistically significant difference between the three groups (p < 0.001 and p = 0.020). Using Aß40 ≥ 42.70 pg/ml as the cut-off point, the sensitivity of the ability of Aß40 to discriminate between AD and NC groups was 80.0%, and specificity was 69.6%. CONCLUSIONS: The plasma Aß40 biomarker was able to distinguish between AD and NC groups. However, the plasma biomarkers in the present research were not able to distinguish between aMCI and NC groups.