Molecular mechanism of human ISG20L2 for the ITS1 cleavage in the processing of 18S precursor ribosomal RNA.

The exonuclease ISG20L2 has been initially characterized for its role in the mammalian 5.8S rRNA 3' end maturation, specifically in the cleavage of ITS2 of 12S precursor ribosomal RNA (pre-rRNA). Here, we show that human ISG20L2 is also involved in 18S pre-rRNA maturation through removing the ITS1 region, and contributes to ribosomal biogenesis and cell proliferation. Furthermore, we determined the crystal structure of the ISG20L2 nuclease domain at 2.9 Å resolution. It exhibits the typical αßα fold of the DEDD 3'-5' exonuclease with a catalytic pocket located in the hollow near the center. The catalytic residues Asp183, Glu185, Asp267, His322 and Asp327 constitute the DEDDh motif in ISG20L2. The active pocket represents conformational flexibility in the absence of an RNA substrate. Using structural superposition and mutagenesis assay, we mapped RNA substrate binding residues in ISG20L2. Finally, cellular assays revealed that ISG20L2 is aberrantly up-regulated in colon adenocarcinoma and promotes colon cancer cell proliferation through regulating ribosome biogenesis. Together, these results reveal that ISG20L2 is a new enzymatic member for 18S pre-rRNA maturation, provide insights into the mechanism of ISG20L2 underlying pre-rRNA processing, and suggest that ISG20L2 is a potential therapeutic target for colon adenocarcinoma.

Successful ageing is associated with falls among older adults in India: a large population based across-sectional study based on LASI.

BACKGROUND: Falls are common in the elderly and can lead to adverse consequences, like injuries, hospitalization, disability even mortality. Successful ageing emerged in sight to assess physical, psychological and social status of older adults. This study is conducted to explore the association between them in a large Indian community-dwelling population. METHODS: Data were based on the wave 1 survey of the Longitudinal Ageing Study in India (LASI). People aged 60 and above with complete information were included. The elderly met five standards including absence of chronic diseases, freedom from disability, high cognitive ability, free from depressive symptoms and active social engagement, were classified into successful agers. The assessment of falls, fall-related injuries and multiple falls depended on interview. Multivariate logistic regression was conducted to find the associations between falls, fall-injury, multiple falls and successful ageing after adjusting both socio-demographic and biological covariates. The log-likelihood ratio test was calculated interactions in subgroups. RESULTS: 31,345 participants in LASI were finally included in our study. Of them, 20.25% reported fall, and 25% were classified into successful agers. After full adjustment, successful ageing was negatively associated with falls (OR 0.70; 95%CI 0.65-0.76) and multiple falls (OR 0.70; 95%CI 0.63-0.78). And the association did not show the significance in older adults with fall-related injuries (OR 0.86; 95%CI 0.72-1.04). CONCLUSIONS: Successful ageing was negatively associated with falls and multiple falls, but not fall-related injuries in older people in India. Future studies are demanded to explore the causal relationship and to reveal the underlying mechanism.

Elevated high-sensitivity C-reactive protein levels increase the risk of new-onset cardiac conduction disorders.

BACKGROUND: Previous studies have reported that inflammatory responses can promote the onset of cardiovascular diseases; however, its association with cardiac conduction disorders remains unclear. The present community-based cohort study aimed to elucidate the effects of inflammatory responses on the risk of developing cardiac conduction disorders. METHODS: After the exclusion of participants failing to meet the inclusion criteria, 86,234 eligible participants (mean age: 50.57 ± 11.88 years) were included. The participants were divided into high-sensitivity C-reactive protein (hsCRP) ≤ 3 mg/L, and hsCRP > 3 mg/L groups based on hsCRP values. Multivariate Cox proportional hazard model was used to analyze the relationship between inflammatory responses and various cardiac conduction disorders. RESULTS: After adjusting for confounding factors, we observed that compared with the hsCRP ≤ 3 mg/L group, the hsCRP > 3 mg/L group exhibited increased risks of atrioventricular block (hazard ratio [HR]:1.64, 95%confidence interval [CI] 1.44-1.87) and left (HR:1.25, 95% CI 1.07-1.45) and right bundle branch block (HR:1.31, 95% CI 1.17-1.47). Moreover, the risk of various cardiac conduction disorders increased for every 1 standard deviation increase in log (hsCRP). The restricted cubic spline function confirmed a linear relationship between log (hsCRP) and the risk of developing cardiac conduction disorders (All nonlinearity P > 0.05). CONCLUSIONS: High hsCRP levels are an independent risk factor for cardiac conduction disorders, and hsCRP levels are dose-dependently associated with the risk of conduction disorders. Our study results may provide new strategies for preventing cardiac conduction disorders.

Correlation between decreased plasma miR-29a and vascular endothelial injury induced by hyperlipidemia.

BACKGROUND: Hyperlipidemia is a major risk factor for vascular endothelial injury and atherosclerosis leading to cardiovascular diseases. Early diagnosis of vascular endothelial injury is important for the prevention and prognosis of cardiovascular diseases. This study aimed to investigate sensitive circulating microRNA (miRNA) as a potential diagnostic biomarker of vascular endothelial injury in a hyperlipidemic rat model. METHODS: The miRNA expression profile was detected by miRNA microarray. The hyperlipidemic rat model was established by intraperitoneal injection of vitamin D3 combined with a high-fat diet. Plasma miRNA levels were measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). RESULTS: No significant difference was found in the types of highly expressed miRNAs between human umbilical artery endothelial cells (HUAEC) and human umbilical vein endothelial cells (HUVEC). A total of 10 highly expressed miRNAs in endothelial cells were selected as candidate miRNAs, including miR-21, miR-126, let-7a, miR-23a, miR-221, miR-125b, miR-26a, miR-29a, miR-16, and miR-100. The plasma levels of let-7a, miR-126, miR-21, and miR-26a were significantly elevated in hyperlipidemic rats at 30 and 50 days after modeling, while the plasma level of miR-29a was significantly decreased. No significant change was found in the plasma levels of miR-125b, miR-23a, miR-221, miR-100, and miR-16. Interestingly, a significant reduction in plasma miR-29 level was detected as early as 20 days after modeling, which was earlier than for soluble intercellular adhesion molecule­1 (sICAM-1). CONCLUSION: The plasma levels of endothelial cell-enriched miRNAs were correlated with vascular endothelial injury induced by hyperlipidemia. miR-29a might serve as a potential early diagnostic biomarker of endothelial injury-related diseases.

GRIN2B Gene Polymorphism in Chronic Ketamine Users.

BACKGROUND AND OBJECTIVES: We examined the allelic variants of N-methyl- d-aspartate receptor 2B (GRIN2B) and analyzed the associations between GRIN2B gene polymorphism with ketamine use conditions and psychopathological symptoms in chronic ketamine users. METHODS: A total of 231 subjects were recruited. Four single nucleotide polymorphisms of GRIN2B, rs1805502, rs7301328, rs890, and rs1806201 were examined in 151 male chronic ketamine users and 80 controls. Psychopathological symptoms in chronic ketamine users were evaluated using the Positive and Negative Syndrome Scale, the Beck Depression Inventory, and the Beck Anxiety Inventory. RESULTS: The genotype CC of rs1806201 had a lower frequency in ketamine users than that in control subjects (χ2 = 8.167, P = .004) and the T allele frequency of rs1806201 in ketamine users was higher than that in the control subjects (P = .009, odds ratio = 2.019 [1.196-3.410]). Ketamine users of genotype TT and CC of rs1806201 had an earlier onset of ketamine use than subjects of genotype TC (P = .038, P = .049, respectively). The dose of ketamine consumption per day of use was higher in genotype GG of rs7301328 than that in those with CG in ketamine users (P = .026). There were no significant differences of the severity of psychopathologic symptoms among different genotypes tested. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: GRIN2B gene polymorphism may play a role in ketamine abuse. (Am J Addict 2020;29:105-110).

The yellow specialist: dronefly Eristalis tenax prefers different yellow colours for landing and proboscis extension.

Droneflies, imagoes of the hoverfly Eristalis tenax, are known to possess a preference for yellow flowers, i.e. they prefer to visit yellow flowers and prefer to extend the proboscis to yellow colours. In this study we disentangle these colour preferences by investigating the landing reaction and proboscis reflex with particular reference to intensity, spectral purity and dominant wavelength of colour stimuli and their UV reflection properties. In multiple-choice tests, naïve and non-trained flies prefer to land on yellow colours independent of their UV reflection characteristics, but also accept blue, white and pink colours if they absorb UV and are of sufficient brightness. Flies trained to land on colours other than yellow still prefer yellow colours to some extent. Moreover, the flies prefer bright over dark yellow colours even if trained to dark yellow ones. The flies refuse to land on dark colours of all hues. Naïve flies exhibit the proboscis reflex only to pure yellow pollen. These experiments show for the first time that landing in droneflies is triggered by a yellow colour independent of its UV reflection properties, but proboscis extension is triggered by yellow colours strongly absorbing blue and UV. The ability to discriminate colours is better than predicted by the categorical colour vision model. The colour preferences in E. tenax represent a fine-tuned ability to visit yellow flowers displaying a UV bull's-eye pattern.

Effect of a real-time tele-transmission system of 12-lead electrocardiogram on the first-aid for athletes with ST-elevation myocardial infarction.

To study the effect of a real-time tele-transmission system of 12-lead electrocardiogram on door-to-balloon time in athletes with ST-elevation myocardial infarction. A total of 60 athletes with chest pain diagnosed as ST-elevation myocardial infarction (STEMI) from our hospital were randomly divided into group A (n=35) and group B (n=25), the patients in group A transmitted the real-time tele-transmission system of 12-lead electrocardiogram to the chest pain center before arriving in hospital, however, the patients in group B not. The median door-to-balloon time was significant shorter in-group A than group B (38min vs 94 min, p<0.01) and the ratio of door-to-balloon time below 90 min was remarkable higher in-group A (94.2% vs 60%, p<0.01). The rate of catheter laboratory occupied was 5.7% in-group A and 40% in group B respectively (p=0.001). There was no statistically difference in mortality between the two groups (5.7% vs 4%, p>0.05). The median length of stay was significant reduced in-group A (5 days vs 7 days, p<0.01). Real-time tele-transmission system of 12 lead electrocardiogram is beneficial to the pre-hospital diagnosis of STEMI.

Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation through activating the NR2B subunits of NMDA receptors.

Corticosterone inhibits the proliferation of hippocampal neural stem cells (NSCs). The removal of corticosterone-induced inhibition of NSCs proliferation has been reported to contribute to neural regeneration. Leptin has been shown to regulate brain development, improve angiogenesis, and promote neural regeneration; however, its effects on corticosterone-induced inhibition of NSCs proliferation remain unclear. Here we reported that leptin significantly promoted the proliferation of hippocampal NSCs in a concentration-dependent pattern. Also, leptin efficiently reversed the inhibition of NSCs proliferation induced by corticosterone. Interestingly, pre-treatment with non-specific NMDA antagonist MK-801, specific NR2B antagonist Ro 25-6981, or small interfering RNA (siRNA) targeting NR2B, significantly blocked the effect of leptin on corticosterone-induced inhibition of NSCs proliferation. Furthermore, corticosterone significantly reduced the protein expression of NR2B, whereas pre-treatment with leptin greatly reversed the attenuation of NR2B expression caused by corticosterone in cultured hippocampal NSCs. Our findings demonstrate that leptin reverses the corticosterone-induced inhibition of NSCs proliferation. This process is, at least partially mediated by increased expression of NR2B subunits of NMDA receptors.

Causal Associations Between Gut Microbiota, Gut Microbiota-Derived Metabolites, and Alzheimer's Disease: A Multivariable Mendelian Randomization Study.

Background: Multiple studies have demonstrated that the gut microbiome is closely related to the onset of Alzheimer's disease, but the causal relationship between the gut microbiome and AD, as well as potential mediating factors, have not been fully explored. Objective: Our aim is to validate the causal relationship between the gut microbiome and the onset of AD and determine the key mechanism by which the gut microbiome mediates AD through blood metabolites using Mendelian randomization (MR) analysis methods. Methods: We first conducted bidirectional and mediating MR analyses using gut microbiota, blood amino acid metabolites, and AD-related single nucleotide polymorphisms as research data. In the analysis process, the inverse variance-weighted average method was mainly used as the primary method, with other methods serving as supplementary evidence. Results: Ultimately, we found that six types of gut bacteria and two blood amino acid metabolites have a causal effect on AD. Subsequent mediation analysis proved that decreased glutamine concentration mediates the negative causal effect of Holdemanella bacteria on AD (mediation ratio of 14.5%), and increased serum alanine concentration mediates the positive causal effect of Parabacteroide bacteria on AD (mediation ratio of 9.4%). Conclusions: Our study demonstrates the causality of Holdemanella and Parabacteroides bacteria in the onset of AD and suggests that the reduced glutamine and increased alanine serums concentration may be key nodes in mediating this effect.

High serum uric acid is a risk factor for arterial stiffness in a Chinese hypertensive population: a cohort study.

The prospective cohort study was to explore the association between serum uric acid (SUA) and arterial stiffness in a Chinese hypertensive population. A total of 7444 participants with hypertension who completed two or more measurements of brachial-ankle pulse wave velocity (baPWV) and baseline SUA detection were followed-up in the Kailuan Study from 2010 to 2020. A restricted cubic spline curve was used to verify whether there was a linear association between baseline SUA and arterial stiffness. A Cox proportional hazard regression model was used to explore the association of between baseline SUA and the incidence of arterial stiffness. Our results showed that the restricted cubic spline curve revealed a linear relationship between baseline SUA and arterial stiffness in total participants (p < 0.001). After follow-up 4.6 ± 2.8 years, Kaplan-Meier survival curves indicated that the risk of arterial stiffness was increased in the high level of baseline SUA (Log-rank p = 0.0002). After adjusting for potential confounding factors, the HR (95% CI) for risk of stiffness was 1.33 (1.17-1.52, p < 0.001) in the highest SUA group. Hierarchical analysis showed that the HRs (95% CI) for risk of arterial stiffness were 1.45 (1.25-1.69), 1.38 (1.19-1.60), 1.41 (1.21-1.64), and 1.35 (1.15-1.58) in the highest SUA group of males, <65 years old, not taking antihypertensive drugs, and failure to achieve the control targets of blood pressure respectively (p < 0.001). These results reveal that high SUA is a risk factor for arterial stiffness in the Chinese hypertensive population.

Structural and biochemical insights into the interaction mechanism underlying HORMAD1 and its partner proteins.

The mammalian HORMA domain-containing protein 1 (HORMAD1) regulates DNA mismatch repair and homologous recombination (HR) repair in many cancers. Here, we show that the structure of human HORMAD1 adopts a self-closed conformation and displays an intra-molecular HORMA domain-closure motif interaction mode. Structural and biochemical data suggest that the interaction modes of the peptide motifs from HORMAD2 and MCM9 with HORMAD1 are highly similar to that of HORMAD1 own closure motif. The peptide motifs from diverse binding partners of HORMAD1 share a conserved Ser-Glu-Pro sequence. Additionally, structural comparison unveiled the HORMA-peptide motif interaction mode diversity among HORMA-containing proteins. Finally, cell-based assays revealed that this HORMA-closure motif interaction pattern contributes to DNA mismatch repair and is required for HORMAD1-dependent HR repair. Together, our results provide structural and biochemical insights into the common theme and functional plasticity of the HORMA domain-containing protein family, and also reveal a universal regulation mechanism for HORMAD1.

Efficacy and Safety of Methylprednisolone for Lung Surgery: a Systematic Review and Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: The administration of methylprednisolone (MP) is a component of perioperative multimodal analgesia that mitigates the potentially deleterious effects of postoperative pain and opioid consumption. However, a systematic evaluation of the efficacy and safety of MP is lacking. The present systematic review and meta-analysis was performed to quantify the potential clinical benefits and risks of perioperative MP in lung surgery. METHODS: We searched seven electronic databases for randomized controlled trials (RCTs) comparing MP with placebo. Coprimary outcomes were rest pain scores, dynamic pain scores, and cumulative morphine equivalent consumption within 24 h postoperatively. RESULTS: A total of 11 trials including 643 participants were selected for our meta-analysis. The results demonstrated that the MP group had a significant difference in coprimary outcomes (rest pain scores, dynamic pain scores, and cumulative morphine equivalent consumption) compared with the placebo group; nevertheless, the improvement was not clinically meaningful based on minimum clinically important differences (MCID). Notably, MP administration reduced serum levels of interleukin (IL)-6 at 6 h (weighted mean difference -20.49 pg/mL; 95% CI -29.94 to -11.04), and decreased the incidence rate of acute lung injury (rate ratio 0.18; 95% CI 0.03-0.98) and cognitive dysfunction (rate ratio 0.43; 95% CI 0.21-0.88) compared with the placebo group. CONCLUSIONS: Our findings suggest that the administration of MP contributed to an insignificant relief in acute postoperative pain for lung surgery in a clinical setting. Future studies should focus on exploring the role of MP in reducing pulmonary and surgical-related complications after lung surgery. CLINICAL TRIAL NUMBER: PROSPERO registration number CRD42022314224.

[New method of processing on Rhei Radix Et Rhizoma and study on quality control of its processing products].

OBJECTIVE: To establish a simple, rapid and usable new method of processing on Rhei Radix Et Rhizoma and the quality control standard on its processing products. METHODS: The studies of processing on Rhei Radix Et Rhizoma were proceed using yellow rice wine as solvent, through spray, soften and dry at 60-70 degrees C. The contents of total and uncombined chrysophanol and emodin in multi-Rhei Radix Et Rhizoma and its processing products were determined by HPLC. RESULTS: The new method of processing on Rhei Radix Et Rhizoma was simple, rapid and usable. The contents of uncombined chrysophanol and emodin in its processing products was 80%. CONCLUSION: This study provides a new method of processing on Rhei Radix Et Rhizoma and quality control standard on its processing products.

Comprehensive analysis of an autophagy-related prognostic model for predicting survival based on TCGA and ICGC database in hepatocellular carcinoma patients.

Background: There is accumulating evidence that autophagic activity is crucial to the development of hepatocellular carcinoma (HCC). Thus, we sought to develop a predictive model based on autophagy-related genes (ARGs) to forecast the prognosis of HCC patients. Methods: Based on expression data from The Cancer Genome Atlas (TCGA) and ARGs from Human Autophagy Database (HADb), the differentially expressed ARGs were screened. The prognosis-related ARGs were identified using a univariate Cox regression analysis. Using multivariate Cox regression analysis, a prognostic model was developed. To assess the predictive value of the model, receiver operating characteristic (ROC) curve, Kaplan-Meier curve, and multivariable Cox regression analyses were conducted. A data cohort gathered independently from the International Cancer Genome Consortium (ICGC) database further verified the model's predictive accuracy. The immune landscape was generated using the TIMER and CIBERSORT algorithms. Finally, the correlation between the prognostic signature and gene mutation status was analyzed by employing "maftools" package. Results: We identified a novel prediction model based on the ARGs of PLD1 and SLC36A1 with significant prognostic values for HCC in both univariate and multivariate Cox regression analysis, and patients were classified into high- or low-risk groups based on their risk scores. High-risk patients had significantly shorter overall survival (OS) times than low-risk patients (P=5e-4). According to the ROC curve analysis, the risk score had a higher predictive value than the other clinical characteristics. Prognostic nomograms were also performed to visualize the relationship between individual predictors and survival rates in patients with HCC. Further, an external independent cohort of ICGC patients provided additional confirmation of the predictive efficacy of the model. We subsequently analyzed the differential immune densities of the two groups and discovered that various immune cells, including naïve B cells, resting memory cluster of differentiation (CD)4 T cells, regulatory T cells, M2 macrophages, and neutrophils, had considerably larger infiltrating densities in the high-risk group than the low-risk group. Conclusions: We established a robust autophagy-related risk model having a certain prediction accuracy for predicting the prognosis of HCC patients. Our findings will contribute to the definition of prognosis and establishment of personalized treatment interventions for HCC patients.

The Choice of Anesthetic Drugs in Outpatient Hysteroscopic Surgery: A Systematic Review and Network Meta-Analysis.

Objective: Hysteroscopy is a minimally invasive gynecologic technique that is widely practiced in outpatient procedures. The choice of anesthesia is a key factor for the surgical outcome and postoperative recovery. This study was conducted to assess the effects of different anesthetic modalities based on dexmedetomidine in outpatient hysteroscopic surgery anesthesia. Methods: We did a systematic review and network meta-analysis of outpatient hysteroscopic surgery anesthesia. We searched Pubmed, Embase, and Cochrane-Library from database inception to December 31, 2021. Duplicate literature was excluded and screened separately for initial screening at three tiers: article title, abstract, and full text before deciding whether to include in this study against the above criteria. Results after analysis of categorical variables were expressed as ORR Ratio (95% CI) and continuous variables were expressed as Mean Difference (95% CI). Data collation and analyses were performed using the gemtc package in the R language. Results: Four trials were finally included with data for 301 participants, three anesthetic drugs, and five anesthetic modalities. A fixed-effects model was used for the different anesthesia modalities without significant heterogeneity (all I2<20%) in the analysis of adverse events (AEs), the incidence of respiratory depression, operative time, and time in the post-anesthesia care unit (PACU). Remimazolam tosylate was associated with a lower incidence of AEs versus dexmedetomidine, and significant differences between dexmedetomidine and propofol were absent. Propofol and various doses of remimazolam tosylate resulted in a lower incidence of respiratory depression versus dexmedetomidine, with an absence of differences between propofol and dexmedetomidine. The operative time for different anesthetic modalities was, in descending order, dexmedetomidine < remimazolam tosylate (0.60 mg/kg/h <0.48 mg/kg/h) < propofol < remimazolam tosylate (1.00 mg/kg/h), despite the absence of intergroup differences. Propofol was associated with a longer time in PACU versus dexmedetomidine and remimazolam tosylate (1.00 mg/kg/h); those of dexmedetomidine and remimazolam tosylate (1.00 mg/kg/h) were similar. The time in PACU for different anesthetic modalities, in descending order, was dexmedetomidine < remimazolam tosylate (1.00 mg/kg/h) < propofol. Propofol was associated with a longer time in PACU versus dexmedetomidine and remimazolam tosylate. Conclusion: In outpatient hysteroscopic surgery anesthesia, dexmedetomidine was associated with a higher incidence of AEs and respiratory depression and a shorter operative time and time in PACU versus remimazolam tosylate and propofol. Remimazolam tosylate showed safety benefits with a similar duration of PACU stay versus dexmedetomidine. Therefore, the choice of anesthetic drugs in outpatient surgery requires consideration of the patient's conditions and preferences.

Chinese expert consensus on assessment of cognitive impairment in the elderly.

Cognitive impairment is a term that refers to the impairment of one or more cognitive domains to varying degrees caused by a variety of reasons. It is under a high prevalence, many risk factors, complex etiology, and great harm to the elderly population. Early screening, diagnosis, and intervention for cognitive impairment in the elderly are of great importance. However, at present, the recognition rate of cognitive impairment for the elderly in China is low, the rate of missed diagnosis is high, and the evaluation is not standardized. This consensus integrates the commonly used cognitive function assessment scales in China and abroad, and aims to popularize the screening of cognitive impairment, standardize the evaluation methods and procedures of cognitive impairment in the elderly, and establish clinical diagnoses, interventions, and follow-up plans in a timely manner.

Association between Perceived Salt Intake and Arterial Stiffness.

To explore the association of perceived salt intake (SI) level with arterial stiffness in the community population in northern China. We enrolled participants who completed the health questionnaire, physical examination, and brachial-ankle pulse wave velocity (baPWV) test during 2010-2019 and divided them into <6 g (low SI), 6-10 g (medium SI), and >10 g (high SI) groups based on their daily SI. The influence of SI on baPWV was analyzed using the multivariate logistic regression model. A total of 36324 subjects, aged (49.10 ± 12.57) years with a male to female ratio of 25934 : 10390, met the inclusion criteria and were enrolled. The average baPWV was (1527.73 ± 355.61) cm/s. Logistic regression analysis showed that after adjusting for other confounders, daily SI>10 g (high SI) was a risk factor for arterial stiffness (baPWV ≥1400 cm/s), with the odds ratio (95% confidence interval [CI]) of 1.17 (1.04-1.31). High SI is independently associated with arterial stiffness.

The Hubei Memory and Aging Cohort Study: Study Design, Baseline Characteristics, and Prevalence of Cognitive Impairments.

BACKGROUND: Despite the improved access to health services in China, inadequate diagnosis and management of dementia are common issues, especially in rural regions. OBJECTIVE: The Hubei Memory & Aging Cohort Study was designed as a prospective study in Central China to determine the prevalence, incidence, and risk factors for dementia and mild cognitive impairment (MCI) among urban and rural older adults. METHODS: From 2018-2020, participants aged ≥65 years were screened, and data regarding their life behaviors, families, socio-economic status, physical and mental health, social and psychological factors, and cognition were collected. Diagnoses of MCI and dementia were made via consensus diagnosis using the Diagnostic and Statistical Manual of Mental Disorders fourth edition criteria. RESULTS: Of 8,221 individuals who completed their baseline clinical evaluation, 4,449 (54.1%) were women and 3,164 (38.4%) were from remote rural areas (average age: 71.96 years; mean education period: 7.58 years). At baseline, 25.98%(95%confidence interval [CI]: 24.99-26.96) and 7.24%(95%CI: 6.68-7.80) of the participants were diagnosed with MCI and dementia, respectively. Prevalence showed a strong relationship with age. The substantial disparities between rural and urban regions in MCI and dementia prevalence and multiple dementia-related risk factors were revealed. Especially for dementia, the prevalence rate in rural areas was 2.65 times higher than that in urban regions. CONCLUSION: Our results suggested that public health interventions are urgently needed to achieve equitable diagnosis and management for people living with dementia in the communities across urban and rural areas.

Population-attributable fractions of risk factors for all-cause dementia in China rural and urban areas: a cross-sectional study.

BACKGROUND: The prevalence of dementia in China, particularly in rural areas, is consistently increasing; however, research on population-attributable fractions (PAFs) of risk factors for dementia is scarce. METHODS: We conducted a cross-sectional survey, namely, the China Multicentre Dementia Survey (CMDS) in selected rural and urban areas from 2018 to 2020. We performed face-to-face interviews and neuropsychological and clinical assessments to reach a consensus on dementia diagnosis. Prevalence and weighted PAFs of eight modifiable risk factors (six classical: less childhood education, hearing impairment, depression, physical inactivity, diabetes, and social isolation, and two novels: olfactory decline and being unmarried) for all-cause dementia were estimated. RESULTS: Overall, CMDS included 17,589 respondents aged ≥ 65 years, 55.6% of whom were rural residents. The age- and sex-adjusted prevalence for all-cause dementia was 9.11% (95% CI 8.96-9.26), 5.19% (5.07-5.31), and 11.98% (11.8-12.15) in the whole, urban, and rural areas of China, respectively. Further, the overall weighted PAFs of the eight potentially modifiable risk factors were 53.72% (95% CI 52.73-54.71), 50.64% (49.4-51.89), and 56.54% (55.62-57.46) in the whole, urban, and rural areas of China, respectively. The eight risk factors' prevalence differed between rural and urban areas. Lower childhood education (PAF: 13.92%) and physical inactivity (16.99%) were primary risk factors in rural and urban areas, respectively. CONCLUSIONS: The substantial urban-rural disparities in the prevalence of dementia and its risk factors exist, suggesting the requirement of resident-specific dementia-prevention strategies.

Comprehensive Analysis to Identify the Epithelial-Mesenchymal Transition-Related Immune Signatures as a Prognostic and Therapeutic Biomarkers in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous disease with the high rates of the morbidity and mortality due to the lack of the effective prognostic model for prediction. Aim: To construct a risk model composed of the epithelial-mesenchymal transition (EMT)-related immune genes for the assessment of the prognosis, immune infiltration status, and chemosensitivity. Methods: We obtained the transcriptome and clinical data of the HCC samples from The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) databases. The Pearson correlation analysis was applied to identify the differentially expressed EMT-related immune genes (DE-EMTri-genes). Subsequently, the univariate Cox regression was introduced to screen out the prognostic gene sets and a risk model was constructed based on the least absolute shrinkage and selection operator-penalized Cox regression. Additionally, the receiver operating characteristic (ROC) curves were plotted to compare the prognostic value of the newly established model compared with the previous model. Furthermore, the correlation between the risk model and survival probability, immune characteristic, and efficacy of the chemotherapeutics were analyzed by the bioinformatics methods. Results: Six DE-EMTri-genes were ultimately selected to construct the prognostic model. The area under the curve (AUC) values for 1-, 2-, and 3- year were 0.773, 0.721, and 0.673, respectively. Stratified survival analysis suggested that the prognosis of the low-score group was superior to the high-score group. Moreover, the univariate and multivariate analysis indicated that risk score [hazard ratio (HR) 5.071, 95% CI 3.050, 8.432; HR 4.396, 95% CI 2.624, 7.366; p < 0.001] and stage (HR 2.500, 95% CI 1.721, 3.632; HR 2.111, 95% CI 1.443, 3.089; p < 0.001) served as an independent predictive factors in HCC. In addition, the macrophages, natural killer (NK) cells, and regulatory T (Treg) cells were significantly enriched in the high-risk group. Finally, the patients with the high-risk score might be more sensitive to cisplatin, doxorubicin, etoposide, gemcitabine, and mitomycin C. Conclusion: We established a reliable EMTri-genes-based prognostic signature, which may hold promise for the clinical prediction.