Atrial fibrillation increases the risk of all-cause dementia, Alzheimer's disease, and vascular dementia: A cohort study of 373, 415 participants in the UK Biobank.

BACKGROUND: Accumulated evidence has highlighted the association between atrial fibrillation and the risk of developing dementia. METHODS: This current cohort study utilized data from the UK Biobank to explore the association between atrial fibrillation (AF) and all-cause dementia (ACD), encompassing its main subtypes (Alzheimer's disease (AD), and vascular dementia (VD)). Cox proportional hazards models were applied to examine the association of AF and dementia with its primary subtypes after adjusting for different sets of covariates. Hazard ratios (HRs) with 95 % confidential intervals (CIs) were estimated to quantify the associated risks. Competing risk model was applied in sensitivity analysis. RESULTS: After exclusion, 373, 415 participants entered the primary analysis. Among these, 27, 934 (7.48 %) were with a history AF at baseline, while 345, 481 (92.52 %) were without. During a mean follow-up of 13.45 years, ACD was diagnosed in 1215 individuals with AF and 3988 individuals without AF. Participants with AF had higher risks of ACD (1.79 [1.67-1.91]), AD (1.48 [1.32-1.65]), and VD (2.46 [2.17-2.80]) in the fully adjusted Cox regression models. Results of subgroup and sensitivity analyses predominantly aligned with the positive associations in primary analysis. LIMITATIONS: The applicability of our findings to diverse ethnicities might require careful consideration and the behind biological mechanisms need to be further revealed. CONCLUSIONS: It indicated that people with atrial fibrillation had an increased future risk of all-cause dementia, Alzheimer's disease, vascular dementia. Atrial fibrillation screening and prevention strategies should take into account to prevent and delay the onset of dementia.

Prevalence and risk factors of anal human papillomavirus infection among men with anal condyloma acuminata by HIV status in ShenZhen, Southeast China: A retrospective cohort study.

Patients with anal condyloma acuminatum (CA) are at risk of developing anal cancer which is associated with oncogenic human papillomavirus (HPV) infection. Investigation of anal HPV prevalence and risk factors can provide effective strategies for the prevention of anal cancer. A retrospective study was conducted among 549 patients with anal CA in the Third People's Hospital of Shenzhen between January 2019 and October 2021. HPV prevalence and HIV antibodies were detected by fluorescent PCR and ELISA, respectively. Logistic regression model and structural equation modeling (SEM) were conducted to analyzed the risk factors of oncogenic HPV infection. The overall prevalence of HPV was 96.72%. Both HPV6 (N = 285, 51.91%) and HPV11 (N = 300, 54.64%) were more than half infected and the most frequent Hr-HPV genotype was HPV16 (N = 138, 25.14%). HIV-positive (AOR: 5.02, 95% CI: 2.98-8.60, p < 0.0001) and history of syphilis (AOR: 4.24, 95% CI: 2.31-8.46, p < 0.0001) were independent risk factors statistically associated with oncogenic HPV infection. Ever had anal sex (AOR: 3.40, 95% CI: 1.28-11.81, p = 0.0267) and age 35 years and older (AOR: 2.79, 95% CI: 1.53-5.15, p = 0.0009) were associated with HPV16 and HPV52, respectively. SEM analyses showed that HIV-positive (b = 1.549, p < 0.001) and history of syphilis (b = 1.450, p < 0.001) had significant positive effects on oncogenic HPV infection. Ever had anal sex (b = 1.243, p = 0.025) and Age (b = 0.043, p = 0.002) positively drived HPV16 and HPV52 infection, respectively. Anal CA patients who are HIV-positive, have a history of syphilis, or at least 35 years old should be considered for Hr-HPV, cytology and other anal cancer related tests to reduce the risk of cancer development.

Risk factors of oncogenic HPV infection in HIV-positive men with anal condyloma acuminata in Shenzhen, Southeast China: a retrospective cohort study.

Background: Human immunodeficiency virus (HIV)-positive patients with anal condyloma acuminata (CA) present an increased risk of anal cancer progression associated with oncogenic human papillomavirus (HPV) infection. It is essential to explore determinants of anal infection by oncogenic HPV among HIV-positive patients with CA. Methods: A retrospective cohort study was performed in HIV-positive patients with CA between January 2019 to October 2021 in Shenzhen, Southeast China. Exfoliated cells were collected from CA lesions and the anal canal of HPV genotypes detected by fluorescence PCR. Unconditional logistic regression analysis was used to probe associations of independent variables with oncogenic HPV infection. Results: Among HIV-positive patients with CA, the most prevalent oncogenic genotypes were HPV52 (29.43%), HPV16 (28.93%), HPV59 (19.20%), and HPV18 (15.96%). Risk of oncogenic HPV infection increased with age at enrollment (COR: 1.04, 95% CI: 1.01-1.07, p = 0.022). In the multivariable analysis, age ≥ 35 years (AOR: 2.56, 95% CI: 1.20-5.70, p = 0.02) and history of syphilis (AOR: 3.46, 95% CI: 1.90-6.79, p < 0.01) were independent risk factors statistically associated with oncogenic HPV infection. History of syphilis (AOR: 1.72, 95% CI: 1.08-2.73, p < 0.02) was also an independent risk factor statistically associated with HPV16 or HPV18 infection. Conclusion: In clinical practice, HIV-positive CA patients aged ≥35 years or with a history of syphilis should carry out HR-HPV testing and even anal cancer-related examinations to prevent the occurrence of anal cancer.

Sequelae of long COVID, known and unknown: A review of updated information.

Over three years have passed since the COVID-19 pandemic started. The dangerousness and impact of COVID-19 should definitely not be ignored or underestimated. Other than the symptoms of acute infection, the long-term symptoms associated with SARS-CoV-2 infection, which are referred to here as "sequelae of long COVID (LC)", are also a conspicuous global public health concern. Although such sequelae were well-documented, the understanding of and insights regarding LC-related sequelae remain inadequate due to the limitations of previous studies (the follow-up, methodological flaws, heterogeneity among studies, etc.). Notably, robust evidence regarding diagnosis and treatment of certain LC sequelae remain insufficient and has been a stumbling block to better management of these patients. This awkward situation motivated us to conduct this review. Here, we comprehensively reviewed the updated information, particularly focusing on clinical issues. We attempt to provide the latest information regarding LC-related sequelae by systematically reviewing the involvement of main organ systems. We also propose paths for future exploration based on available knowledge and the authors' clinical experience. We believe that these take-home messages will be helpful to gain insights into LC and ultimately benefit clinical practice in treating LC-related sequelae.

Co-exposure of serum calcium, selenium and vanadium is nonlinearly associated with increased risk of type 2 diabetes mellitus in a Chinese population.

BACKGROUND: Metals play an important role in type 2 diabetes mellitus (T2DM). This study aimed to explore the association of T2DM risk with single metal exposure and multi-metal co-exposure. METHODS: A case-control study with 223 T2DM patients and 302 controls was conducted. Serum concentrations of 19 metals were determined by inductively coupled plasma mass spectrometry (ICP-MS). Those metals with greater effects were screened out and co-exposure effects of metals were assessed by least absolute shrinkage and selection operator (LASSO) regression. RESULTS: Serum calcium (Ca), selenium (Se) and vanadium (V) were found with greater effects. Higher levels of Ca and Se were associated with increased T2DM risk (OR = 2.23, 95%CI: 1.38-3.62, Ptrend = 0.002; OR = 3.16, 95%CI: 1.82-5.50, Ptrend < 0.001), but higher V level was associated with decreased T2DM risk (OR = 0.58, 95%CI: 0.34-0.97, Ptrend < 0.001). Serum Ca and V concentrations were nonlinearly associated with T2DM risk (Poverall < 0.001, Pnonliearity < 0.001); however, Se concentration was linearly associated with T2DM risk (Poverall < 0.001, Pnonliearity = 0.389). High co-exposure score of serum Ca, Se and V was associated with increased T2DM risk (OR = 3.50, 95%CI: 2.08-5.89, Ptrend < 0.001) as a non-linear relationship (Poverall < 0.001, Pnonliearity = 0.003). CONCLUSIONS: This study suggest that higher levels of serum Ca and Se were associated with increased T2DM risk, but higher serum V level was associated with decreased T2DM risk. Moreover, co-exposure of serum Ca, Se and V was nonlinearly associated with T2DM risk, and high co-exposure score was positively associated with T2DM risk.

First Report of Leaf Spot Caused by Corynespora cassiicola on Acanthus ilicifolius in China.

Acanthus ilicifolius, also referred to as holly mangrove, usually grows in the coastal areas in southern China. It is not only a pioneer species of mangroves but also an important medicinal mangrove plant. In June 2019, leaf spots on A. ilicifolius with disease incidence of about 30 to 40% were observed in about 150 plants in a field located in Zhanjiang City, Guangdong Province, China. The disease mainly occurred on the leaf margins or tips. Initial symptoms of the disease were dark brown spots (5 to 9 mm) surrounded by a yellow halo, that expanded irregularly or semicircularly, until finally the leaves turned chlorotic and defoliated. Six samples of symptomatic leaves were excised, surface sterilized with 75% ethanol 30 s, 0.1% HgCl2 30 s, and rinsed three times with sterile water, and cut into small pieces (5 mm × 5 mm), placed on potato dextrose agar (PDA) at 25°C and darkness, and two isolates with different morphological characteristics were obtained after 3 days. For pathogenicity tests of the isolates, wounded and non-wounded leaves were inoculated. Fresh wounds were made with a sterile needle. Mycelial plugs from 8-day-old cultures of two isolates, ALY1 and ALY2, on PDA were inoculated on adaxial surface of wounded and non-wounded healthy young leaves of the A. ilicifolius seedlings (2 years old, 4 leaves per plant, 2 replicate plants per isolate), covered with wet cotton and kept in moist chambers at 25 ± 1°C, 80% relative humidity. Leaves inoculated with sterile PDA plugs were used as the control. After 3-5 days, the wounded and non-wounded leaves inoculated with ALY1 showed symptoms of leaf spots, similar to those observed in the field, while leaves inoculated with ALY2 and the control leaves remained symptomless. The pathogenicity tests were repeated three times under the same conditions and similar results were observed. ALY1 was confirmed as the pathogen causing the leaf spot. On PDA, ALY1 produced a gray to grayish brown colony. The conidia were obclavate to cylindrical, straight to slightly curved, pale brown, with 6 to 18 pseudosepta, 62.5 to 225.0×3.8 to 14.8 µm (n=17). According to the morphological characteristics, ALY1 was preliminarily identified as Corynespora cassiicola (Zhang et al.2018). For molecular identification, the internal transcribed spacer (ITS), the actin gene (ACT), the ß-tubulin gene (TUB2) and translation elongation factor 1-alpha gene (TEF1-α) of the three single-spore isolates from ALY1 (ALY1-1 to ALY1-3) were amplified and sequenced with primers ITS4/ITS5 (White et al.1990), ACT512F/ACT783R(Carbone and Kohn 1999), T1/T2 (Glass and Donaldson 1995), and EF1-728F/EF1-986R (O'Donnell et al.1998) respectively. The ITS region of ALY1 (-1, -2, -3) (GenBank accession number MN860006, -07, -08) was 99-100% identical (579/585, 586/586, 581/584 base pairs) to a corresponding ITS (MH255527) of C. cassiicola. Similarly, the ACT (MN887504, -05, -06), TUB2 (MN887507, -08, -09) and TEF1-α (MN887501, -02, -03) were 100% (342/342, 342/342, 342/342 base pairs), 100% (664/664, 662/662, 664/664 base pairs) and 100% (290/290, 290/290, 290/290 base pairs) to corresponding genes FJ853033, MH763700, and MK589886 sequences of C. cassiicola in GenBank, respectively. Phylogenetic tree generated with MEGA7 by the neighbor-joining analysis revealed that the isolate's ITS, ACT, TUB2 and TEF1-α sequences were grouped in the same clade to C. cassiicola. Based on both the morphological characteristics and sequences analyses, the pathogen causing leaf spot of A. ilicifolius was identified as C. cassiicola. This species had been reported on the A. ilicifolius in Guam America and Hong Kong China (Lu et al. 2000; Zhuang 2001; Dixon et al. 2009; Sumabat et al. 2018). The best of our knowledge, it is the first report of C. cassiicola causing leaf spot of A. ilicifolius in China. This disease may a potential threat to A. ilicifolius along the coastal regions of southern China.

Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension.

The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease (COVID-19) patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are associated with clinical outcomes remains unknown. COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors. We observed that patients receiving ACEI or ARB therapy had a lower rate of severe diseases and a trend toward a lower level of IL-6 in peripheral blood. In addition, ACEI or ARB therapy increased CD3 and CD8 T cell counts in peripheral blood and decreased the peak viral load compared to other antihypertensive drugs. This evidence supports the benefit of using ACEIs or ARBs to potentially contribute to the improvement of clinical outcomes of COVID-19 patients with hypertension.

Association of UCP1 polymorphisms with type 2 diabetes mellitus and their interaction with physical activity and sedentary behavior.

BACKGROUND: Uncoupling protein 1 (UCP1) has been reported to be associated with type 2 diabetes mellitus (T2DM) in different populations, however, little is reported in Chinese population. The present study aimed to explore the association between some polymorphisms of UCP1 with T2DM and the interactions between UCP1 and physical activity/sedentary behavior (PA/SB) lifestyle in Chinese population. METHODS: Three polymorphisms (rs1472268, rs3811790 and rs3811791) were genotyped in 929 T2DM patients and 1044 nondiabetic controls. The data of PA and SB were acquired. Logistic regression and linear regression were conducted to assess the association of UCP1 and T2DM and related traits. RESULTS: The CC genotype of rs3811791 was significantly associated with an increased risk of T2DM [odds ratio (OR) = 1.42, P = 0.042] and a higher level of triglyceride (TG) (ß = 0.048, P = 0.034). This association still existed in the group of SB ≥ 3 h/d (OR = 1.66, P = 0.009) and the group of PA ≥ 150 min/week and SB ≥ 3 h/d (OR = 1.60, P = 0.034). In the group of PA < 150 min/week and SB < 3h/d, CC genotype was associated with a higher level of homeostatic model assessment of insulin resistance (HOMA-IR) index, and in the group of PA < 150 min/week and SB ≥ 3 h/d, CC genotype was associated with increased level of TG and decreased high-density lipoprotein cholesterol (HDL-C). CONCLUSION: This study suggests that rs3811791 of UCP1 may be associated with T2DM and TG. Moreover, we demonstrate that SB interacted with rs3811791 of UCP1 was associated with T2DM, and PA interacted with rs3811791 of UCP1 was associated with the level of HOMA-IR, HDL-C, and TG.

Exploring the mechanism of clear cell renal cell carcinoma metastasis and key genes based on multi-tool joint analysis.

Clear cell renal cell carcinoma (ccRCC) is a highly invasive urological malignant tumor that results in shorter patient survival. At present, the mechanism of ccRCC metastasis is not clear. We explored the possible mechanisms of ccRCC metastasis by analyzing the transcriptome of ccRCC patients from the Cancer Genome Atlas (TCGA) database. Comparing the differences in transcriptome in patients with and without metastasis, we found 323 differential genes (|log2FoldChange| > 1 and P < 0.001). KEGG and GO enrichment analyses of differentially expressed genes (DEGs) suggest that the transfer mechanism of ccRCC may be related to complement and coagulation cascades and cholesterol metabolism. To explore the key genes affecting tumor metastasis, we analyzed the association of these genes with patient survival time and found that 16 genes were significantly associated (P < 0.05). We compared the differences in expression of these 16 genes between ccRCC patients and the normal population, and the results showed that TF and B4GALNT1 were overexpressed in patients. Co-expression gene analysis indicated that TF may participate in the metastasis of cancer through the complement system and mucopolysaccharide biosynthesis. B4GALNT1 may affect metastasis through focal adhesion, calcium signaling pathways, and Hippo signaling pathways. Our studies suggest that the complement system and the coagulation cascade, cholesterol metabolism, calcium pathway and iron transport may be associated in the mechanism of metastasis. TF and B4GALNT1 may be the key genes for metastasis, and they may be potential diagnostic markers and therapeutic targets for ccRCC.

Pleiotropy of glycogen synthase kinase-3 inhibition by CHIR99021 promotes self-renewal of embryonic stem cells from refractory mouse strains.

BACKGROUND: Inhibition of glycogen synthase kinase-3 (GSK-3) improves the efficiency of embryonic stem (ES) cell derivation from various strains of mice and rats, as well as dramatically promotes ES cell self-renewal potential. ß-catenin has been reported to be involved in the maintenance of self-renewal of ES cells through TCF dependent and independent pathway. But the intrinsic difference between ES cell lines from different species and strains has not been characterized. Here, we dissect the mechanism of GSK-3 inhibition by CHIR99021 in mouse ES cells from refractory mouse strains. METHODOLOGY/PRINCIPAL FINDINGS: We found that CHIR99021, a GSK-3 specific inhibitor, promotes self-renewal of ES cells from recalcitrant C57BL/6 (B6) and BALB/c mouse strains through stabilization of ß-catenin and c-Myc protein levels. Stabilized ß-catenin promoted ES self-renewal through two mechanisms. First, ß-catenin translocated into the nucleus to maintain stem cell pluripotency in a lymphoid-enhancing factor/T-cell factor-independent manner. Second, ß-catenin binds plasma membrane-localized E-cadherin, which ensures a compact, spherical morphology, a hallmark of ES cells. Further, elevated c-Myc protein levels did not contribute significantly to CH-mediated ES cell self-renewal. Instead, the role of c-Myc is dependent on its transformation activity and can be replaced by N-Myc but not L-Myc. ß-catenin and c-Myc have similar effects on ES cells derived from both B6 and BALB/c mice. CONCLUSIONS/SIGNIFICANCE: Our data demonstrated that GSK-3 inhibition by CH promotes self-renewal of mouse ES cells with non-permissive genetic backgrounds by regulation of multiple signaling pathways. These findings would be useful to improve the availability of normally non-permissive mouse strains as research tools.

Relationships between distributions of longevous population and trace elements in the agricultural ecosystem of Rugao County, Jiangsu, China.

Soil, plant, and water, as well as trace elements they contain, can influence human health through the food chain. A survey was conducted on distributions of trace elements in soils, plants, and drinking water in Rugao County, Jiangsu Province, China, an agricultural area with a high level of centenarians and nonagenarians. The ratio of people over 90 years old per 100,000 inhabitants (90-rate) based on village (about 4,000 residents in 4 km(2)) was correlated with trace elements in soil, drinking water, and rice by means of correlation analysis and/or principal component analysis. Although the average 90-rate in the whole area was as high as 277, the rates were not uniform across the entire region. The 90-rate in the area of loamy and strongly-developed Anthrosols and Cambosols was about 330, significantly higher than the 255 in the areas of sandy and strongly-developed Cambosols and of clayey and weakly-developed Cambosols. The concentrations of available Se, B, Ni, and Mo in soils of the area with the high 90-rate were markedly greater than those in the area with the low 90-rate. This was demonstrated by highly positive correlations between the 90-rate and available Se (r = 0.33), B (r = 0.21), Ni (r = 0.17) and Mo (r = 0.17) at the p < 0.01 level and high loadings of available Se (0.851), B (0.535), Ni (0.594) and Mo (0.394) in the longevous factor. Similar relationships between the available elements in soils and elements in water and rice were found. These results suggest that: (1) the available forms of elements in soil were more crucial to elemental bio-availability in the ecosystem and human health than total elements in soil; and (2) the element association above might have affected the 90-rate positively and could be an important environmental geochemical factor influencing the longevity of humans.