Spin-dependent thermoelectric transport properties of Cr-doped blue phosphorene.

We systematically investigate the thermoelectric (TE) properties of the Cr-doped blue phosphorene (blue-P) along the armchair and zigzag directions. First, we find the semiconducting band structure of the blue-P will become spin-polarized due to the Cr-doping, and can be seriously changed by the doping concentration. Then we show the Seebeck coefficient, the electronic conductance, the thermal conductance, and the figures of meritZTs are all dependent on the transport directions and doping concentration. However, two pairs of the peaks of the charge and spinZTs can be always observed with the low-height (high-height) pair on the side of the negative (positive) Fermi energy. In addition, at temperature 300 K the extrema of the charge (spin)ZTs of the blue-P along the two directions are kept to be larger than 22 (90) for the different doping concentrations and will be further enhanced at lower temperature. Therefore, we believe the Cr-doped blue-P should be a versatile high-performance TE material which may be used in the fields of the thermorelectrics and spin caloritronics.

Electronic structures, transport properties, and optical absorption of bilayer blue phosphorene nanoribbons.

Based on first-principles density functional theory and nonequilibrium Green's function, we study the electronic band structures, the electronic transport properties, and the optical absorption of bilayer blue phosphorene nanoribbons (BPNRs). Both bilayer armchair BPNRs (a-BPNRs) and zigzag BPNRs (z-BPNRs) behave as semiconductors in the narrow nanoribbon case and metals in the wide nanoribbon case, sharply different from their monolayer counterparts where the monolayer a-BPNRs (z-BPNRs) are always semiconducting (metallic). This indicates that interlayer couplings or the increasing layer number may induce the switching of the conductivity of the monolayer BPNRs, which is absent in graphene and phosphorene nanoribbons. Furthermore, we explore the edge states of the energy bands near Fermi energy, and find that there are almost no pure edge-state band branches in the bilayer BPNRs, which can be attributed to the interlayer couplings between the edge-states in one layer and the bulk-states in the other. Consequently, the resulting complex band structures cannot be directly analyzed any more in the framework of the two-body coupling picture just according to the simple band structures of the monolayer BPNRs. Finally, we present the current-voltage characteristics and the optical absorption of the bilayer a-BPNRs and z-BPNRs. The influences of the nanoribbon width and the interlayer couplings on the current and the anisotropic optical absorption can be understood based on the complex energy band structures. This research should be an important reference of extending the field of BPNRs from the monolayer to the bilayer case, and deepen the understanding of the difference between the monolayer and bilayer nanoribbons in different materials.

[Regional disparities in trends of global gastric cancer incidence and mortality from 1990 to 2019].

Objective: To depict gastric cancer burden trends globally and analyze geographical and socioeconomic disparities among different countries and territories. Methods: We extracted the data from Global Burden of Disease 2019 Database. We conducted the Joinpoint regression and calculated the average annual percent change (AAPC) and corresponding 95% confidence interval (CI) for age-standardized gastric cancer incidence and mortality from 1990 to 2019. Linear regression was performed to measure the association of sociodemographic index (SDI) with each country's gastric cancer incidence and mortality AAPC. We applied the age-period-cohort analysis to assess the cohort effect on gastric cancer incidence and mortality. Results: The AAPCs for gastric cancer age-standardized incidence and mortality rates from 1990 to 2019 were -1.27% (95% CI: -1.43%, -1.11%) and -1.87% (95% CI: -2.01%, -1.72%), respectively. SDI levels were negatively associated with AAPCs, which means that countries with higher SDI had higher AAPC (P<0.001). The decrease of gastric cancer burden in countries with low or medium SDI levels was slower than that globally. The age-period-cohort analysis indicated that countries with higher SDI levels had more apparent decline in birth cohort effects from 1900 to 1999. Conclusions: Countries with different socioeconomic levels have various decreasing rates for gastric cancer incidence and deaths. Countries with higher SDI levels have higher declining rates for gastric cancer burden.

[A comparative analysis of the distribution of the high-risk population of upper gastrointestinal cancer and endoscopic screening compliance in two urban areas and two rural areas in China].

Objective: To analyze and compare the distribution of the high-risk population of upper gastrointestinal (UGI) cancer and the factors influencing the compliance rate of endoscopic screening in urban China and rural China. Methods: From 2015 to 2017, an epidemiological survey was conducted on residents aged 40-69 in two rural areas (Luoshan county of Henan province, Sheyang county of Jiangsu province) and two urban areas (Changsha city of Hunan province, Harbin city of Heilongjiang province). As a result, high-risk individuals were recommended for endoscopic screening. Chi-square χ(2) test was used to compare the high-risk rate of UGI cancer between urban and rural residents. In addition, the multivariate logistic regression model was used to analyze the factors influencing the compliance rate of endoscopic screening. Results: A total of 48, 310 residents aged 40-69 were enrolled in this study, including 22 870 (47.34%) residents from rural areas and 25 440 (52.66%) residents from urban areas. A total of 23 532 individuals were assessed with a high risk of UGI cancer, with an overall risk rate of 48.71%. A higher proportion of participants with high risk was observed in rural China (56.17%, 12 845/22 870) than in urban China (42.01%, 10 687/25 440). A total of 10 971 high-risk individuals with UGI cancer participated in endoscopic screening, with an overall compliance rate of 46.62% (10 971/23 532), 45.15% (5 799/12 845) in rural China, and 48.40% (5 172/10 687) in urban China. In rural population, the compliance rate of endoscopic screening was higher in those of females, aged 50-69 years, primary school education or above, high income, a family history of UGI cancer, history of gastric and duodenal ulcer, history of reflux esophagitis, and history of superficial gastritis, but lower in smokers (P<0.05). Among the urban population, the compliance rate of endoscopic screening was higher in those aged 40-49 years, uneducated, low income, family history of UGI cancer, history of reflux esophagitis, history of superficial gastritis, but lower in smokers (P<0.05). Conclusions: The proportion of participants with high risk of UGI cancer in rural areas is higher than that of urban areas. The compliance rates of endoscopic screening in urban and rural areas are low, and influencing factors of endoscopic screening exhibit some differences in rural China and urban China.

[The relationship between insulin resistance and risk of long-term mortality in people without diabetes: a 30-year follow-up of the Daqing Diabetes Study].

Objective: To determine whether insulin resistance is associated with all-cause mortality in subjects without diabetes. Methods: A total of 505 participants without diabetes, 198 with normal glucose tolerance (NGT) and 307 with impaired glucose tolerance (IGT), were recruited from the Daqing Diabetes Study. The participants were followed up for 30 years. They were stratified into three groups (tertiles) according to baseline homeostasis model assessment of insulin resistance(HOMA-IR) levels, as the HOMA-IR 0, the HOMA-IR 1 and the HOMA-IR 2 groups, to assess the predictive effect of insulin resistance on risk of all-cause mortality. Results: During the 30-year follow-up, 52, 56 and 78 participants died across the three HOMA-IR groups, respectively. The corresponding mortality per 1 000 person-years (95%CI) were 12.12 (9.56-15.01), 13.10 (10.46-16.03) and 19.91 (16.73-23.15), respectively. Participants in the HOMA-IR 2 group had a significantly higher risk of death than those in the HOMA-IR 0 group after adjustment of age, sex and smoking status (HR=1.97,95%CI 1.38-2.81, P<0.001). Cox analyses showed that a one standard deviation increase in HOMA-IR was associated with a 22% increase in the mortality after adjustment of potential confounders (HR=1.22, 95%CI 1.08-1.39, P=0.002). Conclusions: Insulin resistance is associated with increased risk of all-cause death in Chinese people without diabetes, suggesting that improving insulin resistance could be beneficial for people without diabetic in reducing risk of long-term all-cause mortality.

[A multicenter, double-blind, randomized controlled clinical trial comparing ergometrine with oxytocin and oxytocin alone for prevention of postpartum hemorrhage at cesarean section].

Objective: To compare oxytocin combined with ergometrine with oxytocin alone in terms of primary prophylaxis for postpartum hemorrhage (PPH) at the time of cesarean section (CS). Methods: This was a multicenter double-blind randomized controlled interventional study comparing ergometrine combined with oxytocin and oxytocin alone administered at CS. From December 2018 to November 2019, a total of 298 parturients were enrolled in 16 hospitals nationwide. They were randomly divided into experimental group (ergometrine intra-myometrial injection following oxytocin intravenously; 148 cases) and control group (oxytocin intra-myometrial injection following oxytocin intravenously; 150 cases) according to 1∶1 random allocation. The following indexes were compared between the two groups: (1) main index: blood loss 2 hours (h) after delivery; (2) secondary indicators: postpartum blood loss at 6 h and 24 h, placental retention time, incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution; (3) safety indicators: nausea, vomiting, dizziness and other adverse reactions, and blood pressure at each time point of administration. Results: (1) The blood loss at 2 h after delivery in the experimental group [(402±18) ml] was less than that in the control group [(505±18) ml], and the difference was statistically significant (P<0.05). (2) The blood loss at 6 h and 24 h after delivery in the experimental group were less than those in the control group, and the differences were statistically significant (all P<0.05). There were no significant differences between the two groups in the incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution (all P>0.05). (3) Adverse reactions occurred in 2 cases (1.4%, 2/148) in the experimental group and 1 case (0.7%, 1/150) in the control group. There was no significant difference between the two groups (P>0.05). The systolic blood pressure within 2.0 h and diastolic blood pressure within 1.5 h of drug administration in the experimental group were higher than those in the control group, and the differences were statistically significant (P<0.05), but the blood pressure of the two groups were in the normal range. Conclusion: The use of ergometrine injection in CS could reduce the amount of PPH, which is safe and feasible.

[Research advances in the relationship of dietary factors and prostate cancer risk].

Prostate cancer is the second most common malignancy in men worldwide. An increasing trend for prostate cancer incidence was observed in China. Enormous studies have been conducted to investigate the association between dietary factors and prostate cancer, however conflicted results were obtained. Red meat, processed meat, and dairy products consumption were reported to be associated with the increased prostate cancer risk, while tomatoes, soybeans and green tea might reduce the risk of prostate cancer occurance. However, no consensus could be reached without strong evidence. Furthermore, further studies are needed to investigate the association between vitamin and mineral supplements and prostate cancer risk. Some studies reported that men with higher dietary inflammatory index scores increased prostate cancer risk. There may be a long susceptible period when dietary factors affect prostate cancer risk, which poses challenges for collecting exposure and the follow-up. Measure bias and detection bias are the main reasons which impair the authenticity of studies on the relationship of dietary factors and prostate cancer risk. Researchers should apply various methods to measure participants' dietary consumption levels and ascertain essential outcomes, such as prostate cancer death. This article reviews updated epidemiological evidences on the association of dietary factors and prostate cancer, aims to benefit future nutritional epidemiology studies focus on the prostate cancer prevention.

[Analysis of Dimethyltryptamine in Captured Suspicious Substances：Three Case Reports].

ABSTRACT: Abstract.

[Identification of New Psychoactive Tryptamines 4-OH-MET and 4-AcO-DMT Using High Resolution Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy].

ABSTRACT: Objective To detect the uncontrolled new psychoactive tryptamines involved in drug-related cases with high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Methods White and brown powder obtained in actual cases were extracted and analyzed by gas chromatography-quadrupole time-of-flight mass spectrometry （GC-QTOF-MS）, ultra-high performance liquid chromatography-linear ion trap quadrupole-orbitrap mass spectrometry （UPLC-LTQ-Orbitrap MS） and 1H-nuclear magnetic resonance spectroscopy （1H-NMR）. Results After detection by GC-QTOF-MS, the components of white powder showed main characteristic fragment ion peaks at m/z 218.141 0 （molecular ion peak）, 72.080 6 （base peak）, etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 219.149 4. The main ions in the secondary mass spectrum under the collision-induced dissociation （CID） mode were m/z 160.076 3 and 72.080 8. After detection by GC-QTOF-MS, the components of brown powder showed main characteristic fragment ion peaks at m/z 246.135 7 （molecular ion peak）, 58.065 1 （base peak）, etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 247.145 0. The main ions in the secondary mass spectrum under CID mode were m/z 202.087 1, 160.076 3 and 134.060 5. NIST 17 library retrieval and 1H-NMR confirmed that the white powder and brown powder contained new psychoactive tryptamines 4-OH-MET and 4-AcO-DMT, respectively. Conclusion GC-QTOF-MS, UPLC-LTQ-Orbitrap MS and 1H-NMR can be used together to identify unknown new psychoactive substances.

Determination of Azide Ions in Blood by Pentafluorobenzyl Derivation Followed by GC-MS.

ABSTRACT: Objective To establish a method for determination of the azide ions in blood by gas chromatography-mass spectrometry （GC-MS） following pentafluorobenzyl derivatization. Methods A blood sample of 0.2 mL was placed into a 10 mL glass test tube, and the internal standard sodium cyanide, derivatization reagent pentafluorobenzyl bromide and catalyst tetradecyl benzyl dimethyl ammonium chloride were added in turn. After vortex mixing, the mixture was heated with low-power microwave for 3 min. After centrifugation, the organic phase was taken for GC-MS analysis. Results The azide ions in blood had a good linear relationship in the mass concentration range of 0.5 to 20 µg/mL. The lowest detection limit was 0.25 µg/mL and the relative recovery was 91.36%-94.58%. The method was successfully applied to a case of death from sodium azide poisoning. The mass concentration of azide ions in the blood of the dead was 11.11 µg/mL. Conclusion The method developed in this paper has strong specificity and is easy to operate, which is suitable for the rapid detection of azide ions in blood.

[Course of Revision of the Diagnosis and Treatment Protocol for COVID-19 and the Forensic Contribution].

ABSTRACT: From January 15 to March 3, 2020, seven editions of the guidelines for the diagnosis and treatment of COVID-19 have been issued successively by the National Health Commission of the People's Republic of China, and the guidelines' name was changed from Guidelines for Diagnosis and Treatment of Novel Coronavirus Pneumonia to Diagnosis and Treatment for COVID-19. It optimized and perfected the etiology, clinical manifestations and types, diagnostic procedures and specific treatment measures of the disease, so that the clinical management of the cases was more scientific. In the revision process of guidelines for diagnosis and treatment, forensic medicine experts have also made some positive suggestions on clinical diagnosis and treatment. Especially regarding the pathological changes of COVID-19, they have repeatedly called for rapid autopsy at different levels. With the support, understanding and cooperation of all parties, pathological examination of more than ten cases of the remains were carried out, which made an important contribution to the understanding of the clinical characteristics and pathological characteristics of the disease and the improvement of treatment plans.

Identification of Tiletamine, Zolazepam and Their Metabolites in Drug Facilitated Sexual Assault by GC-QTOF-MS.

ABSTRACT: Objective To identify tiletamine, zolazepam and their metabolites in samples from drug facilitated sexual assault by gas chromatography-quadrupole time of flight mass spectrometry （GC-QTOF-MS）. Methods Urine samples of victims were collected, and detected by GC-QTOF-MS after liquid-liquid extraction and concentration. The molecular formula of fragments ions was identified by determination of accurate mass numbers, to detect related substances. Results Tiletamine, zolazepam, three metabolites of tiletamine and two metabolites of zolazepam were identified in urine samples from actual cases. Conclusion GC-QTOF-MS provides abundant and accurate information of fragment ions mass numbers, which can be used for qualitative identification of tiletamine, zolazepam and their metabolites in drug facilitated sexual assault.

Draft genome of the fungicidal biological control agent Burkholderia anthina strain XXVI.

Burkholderia anthina XXVI is a rhizosphere bacterium isolated from a mango orchard in Mexico. This strain has a significant biological control activity against the causal agent of mango anthracnose, Colletotrichum gloeosporioides, likely through the production of siderophores and other secondary metabolites. Here, we present a draft genome sequence of B. anthina XXVI (approximately 7.7 Mb; and G + C content of 67.0%), with the aim of gaining insight into the genomic basis of antifungal modes of action, ecological success as a biological control agent, and full biosynthetic potential.

[Data mining of esophageal squamous cell carcinoma from The Cancer Genome Atlas database].

Objective: To deeply investigate the gene expression profiles of esophageal squamous cell carcinoma (ESCC) and the relationship of gene expression levels with prognosis from The Cancer Genome Atlas (TCGA) database. Methods: RNA-seq V2 data of 11 normal samples and 81 esophageal squamous cell carcinoma patients, and their corresponding clinical data were downloaded from The Cancer Genome Atlas database. Differentially expressed genes between normal and tumor samples were identified by using edgeR package. Gene function enrichment analyses of differentially expressed genes were conducted. A protein-protein interaction network based on differentially expressed genes was constructed by using STRING database and the hub genes were identified based on the created gene co-expression network. In addition, survival analysis was performed. Results: Totally, 2 788 genes were identified as differential expression. Among these, 1 168 genes were up-regulated and 1 620 genes were down-regulated in tumor cases compared with normal samples. Up-regulated genes were enriched in cell cycle, DNA replication and mismatch repair pathways, while down-regulated genes were enriched in metabolic pathways. 707 genes and their 3 428 interactions were identified by protein-protein interaction analysis. Genes with copy number amplifications were considered to interact with other crucial genes. 10 co-expression modules were identified based on the gene co-expression network analysis and the ribosomal protein genes were illustrated to be correlated with tumor locations of ESCC patients (P=0.003). The 3-years survival rates of high and low expression of TNFRSF10B groups were 82.5% and 15.1%, respectively. Similarly, the 3-years survival rates of high and low expression of DDX18 groups were 82.4% and 15.2%, respectively. The survival differences stratified by these two genes were statistically significant (both P<0.1). Conclusions: The analysis results of TCGA database showed that ribosomal protein genes are correlated with tumor locations of ESCC patients. Low expressions of TNFRSF10B and DDX18 are associated with poor prognose of ESCC patients. Consequently, TNFRSF10B and DDX18 may serve as predictive markers for ESCC patients.

Research gaps in the management and prevention of cutaneous squamous cell carcinoma in organ transplant recipients.

Although tremendous progress has been made in recent years in skin cancer care for organ transplant recipients, significant gaps remain in data-driven clinical guidelines, particularly for the treatment and prevention of cutaneous squamous cell carcinoma (cSCC), the most common malignancy among this population. In this review, we aim to summarize current knowledge around the management of cSCC and highlight the most significant gaps in knowledge that continue to pose challenges in the delivery of skin cancer care for organ transplant recipients. We suggest future directions for research that will bridge existing gaps and establish evidence-driven guidelines for primary prevention, screening and treatment of cSCC in this high-risk patient population.

Practice variation in Aspergillus prophylaxis and treatment among lung transplant centers: a national survey.

BACKGROUND: Fungal infections remain a substantial cause of mortality in lung transplant (LTx) recipients, yet no comprehensive consensus guidelines have been established for antifungal prophylaxis and treatment of Aspergillus infection in these patients. METHODS: A cross-sectional study surveyed the directors from 27 of 64 (45.5%) active LTx centers in the United States to examine clinical practice variations in Aspergillus prophylaxis and treatment of colonization and invasive aspergillosis (IA) in LTx recipients. RESULTS: Antifungal prophylaxis increased from 52.3% in 2011 to 77.8% in 2013, with the most common agent being inhaled amphotericin B (61.9%), followed by oral voriconazole (51.9%). A total of 74.1% of centers treat Aspergillus airway colonization, with 80.0% of centers using oral voriconazole. All centers treat IA, with 92.6% using oral voriconazole. The duration of Aspergillus prophylaxis and treatment of colonization or IA varied widely across centers from 3 months to >1 year. A total of 51.9% of centers reported internal practice variations in the treatment of IA. Factors guiding treatment decisions included microbiologic culture and sensitivity (74.1%), ease of administration (59.3%), interaction with other medications (55.5%), side effect profile (51.8%), and center guidelines (48.1%). Although 85.2% of LTx centers recommended routine skin cancer screening for LTx recipients, only 44.4% of LTx centers reported having a dedicated transplant dermatologist. CONCLUSION: Most active US LTx centers currently employ antifungal prophylaxis and treat Aspergillus colonization and IA, although choice of agent, route of administration, and duration of therapy across and within centers continue to differ substantially. The number of transplant dermatologists available among US LTx centers is limited. Overall, a strong need exists for more comprehensive consensus guidelines to direct antifungal prophylaxis and treatment of Aspergillus infection in LTx recipients.

Areas of potential suitability and survival of Dendroctonus valens in China under extreme climate warming scenario.

The areas in China with climates suitable for the potential distribution of the pest species red turpentine beetle (RTB) Dendroctonus valens LeConte (Coleoptera: Scolytidae) were predicted by CLIMEX based on historical climate data and future climate data with warming estimated. The model used a historical climate data set (1971-2000) and a simulated climate data set (2010-2039) provided by the Tyndall Centre for Climate Change (TYN SC 2.0). Based on the historical climate data, a wide area was available in China with a suitable climate for the beetle in which every province might contain suitable habitats for this pest, particularly all of the southern provinces. The northern limit of the distribution of the beetle was predicted to reach Yakeshi and Elunchun in Inner Mongolia, and the western boundary would reach to Keerkezi in Xinjiang Province. Based on a global-warming scenario, the area with a potential climate suited to RTB in the next 30 years (2010-2039) may extend further to the northeast. The northern limit of the distribution could reach most parts of south Heilongjiang Province, whereas the western limit would remain unchanged. Combined with the tendency for RTB to spread, the variation in suitable habitats within the scenario of extreme climate warming and the multiple geographical elements of China led us to assume that, within the next 30 years, RTB would spread towards the northeast, northwest, and central regions of China and could be a potentially serious problem for the forests of China.

Effect of curcumin on p38MAPK expression in DSS-induced murine ulcerative colitis.

The aim of this study was to determine the therapeutic effect of curcumin on dextran sulfate sodium-induced ulcerative colitis (UC) and to explore the related mechanism. Sixty mice were randomly divided into 6 groups. A group was the normal control group; B group was the model group; C group was the 1.5 mg/kg dexamethasone group based on the B group; and D, E and F groups were 15, 30, and 60 mg/kg curcumin groups, respectively, based on the B group. The mice were killed 7 days after treatment; the expression of TNF-α and MPO in colon tissue was determined with ELISA, and colon p-p38MAPK and p38MAPK mRNA expression was evaluated by immunohistochemistry and RT-PCR, respectively. In the C, D, E, and F groups, TNF-α and MPO levels significantly decreased (P < 0.05), and the expression of p-p38MAPK also significantly decreased (P < 0.01). The expression of p38MAPK mRNA in the C, D, E, and F groups decreased (P < 0.01), and there was a statistically significant difference between the E and F groups (P < 0.01). Curcumin had a therapeutic effect, which probably played a role in UC treatment by inhibiting the p38MAPK signaling pathway, thereby reducing the release of TNF-α.

Roles of Fas/Fasl, Bcl-2/Bax, and Caspase-8 in rat nonalcoholic fatty liver disease pathogenesis.

The aim of this study was to investigate the roles of Fas/FasL, Bcl-2/Bax, and Caspase-8 mRNA expressions in nonalcoholic fatty liver disease (NAFLD). The apoptosis percentage was measured by flow cytometry, the immunohistochemical assay was performed for the determination of Fas, FasL, Bcl-2, and Bax expressions, and a real-time polymerase chain reaction (PCR) assay was performed to detect Caspase-8 mRNA expression. Flow cytometry showed that the apoptosis percentage of the rat liver in the experimental group increased, which increased more obviously with the extension of modeling time. Immunohistochemistry showed that with increasing hepatic steatosis, Fas and FasL protein staining intensified and the number of positive cells increased; the number of positive cells for Bcl-2 and Bax gradually increased on the 4th, 8th, and 12th weeks in the experimental group, whereas the Bcl-2/Bax ratio decreased. The real-time PCR assay showed that Caspase-8 mRNA expression increased with increasing hepatic steatosis and inflammation, exhibiting a progressively rising trend. Hepatocyte apoptosis could promote NAFLD progression; Fas, FasL, and Caspase-8 mRNA activation were important contributing factors to NAFLD. The upregulation of Bax and Bcl-2 expression might be one important mechanism of the apoptosis in NAFLD.

Non-Genetic Risk Factors of Alzheimer's Disease: An Updated Umbrella Review.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by intricate genetic and environmental etiology. The objective of this study was to identify robust non-genetic risk factors for AD through an updated umbrella review. METHODS: We conducted a comprehensive search of meta-analyses and systematic reviews on non-genetic risk factors associated with AD in PubMed, Cochrane, Embase, and Ovid Medline up to June 30, 2023. After collecting data, we estimated the summary effect size and their 95% confidence intervals. The degree of heterogeneity between studies was assessed using I2 statistics and a 95% prediction interval was determined. Additionally, we evaluated potential excess significant bias and small study effects within the selected candidate studies. RESULTS: The umbrella review encompassed a total of 53 eligible papers, which included 84 meta-analyses covering various factors such as lifestyle, diet, environmental exposures, comorbidity or infections, drugs, and biomarkers. Based on the evidence classification criteria employed in this study, two factors as convincing evidence (Class I), including rheumatoid arthritis (RA), potentially reduced the risk of AD, but diabetes significantly increased the risk of AD. Furthermore, three factors as highly suggestive evidence (Class II), namely depression, high homocysteine, and low folic acid level, potentially increased the risk of AD. CONCLUSION: Our findings highlight several risk factors associated with AD that warrant consideration as potential targets for intervention. However, it is crucial to prioritize the identified modifiable risk factors, namely rheumatoid arthritis, diabetes, depression, elevated homocysteine levels, and low folic acid levels to effectively address this complex neurodegenerative disorder.