Association of Lipid Levels With the Prevalence of Hypertension in Chinese Women: A Cross-Sectional Study Based on 32 Health Check Centers

Background: Dyslipidemia is strongly associated with the development of hypertension. In our previous study, it was shown that elevated TC, LDL-c, and non-HDL-c were associated with the prevalence of hypertension in Chinese men, whereas the relationship between HDL-c and hypertension shifted from no association to a positive association after adjusting for the BMI. To further accumulate epidemiological evidence in Asian women, this study aimed to investigate the relationship between lipid profile and prevalence of hypertension in Chinese adult women. Methods: This is a cross-sectional study including 54,099 Chinese women aged>20 years at 32 health screening centers in 11 cities from 2010-2016. The original data were obtained from DATADRYAD database (www.datadryad.org). Besides, the overall women were classified into non-hypertensive and hypertensive groups based on baseline blood pressure levels. Differences between the two groups were examined by Man-Whitney test or Chi-square test. Spearman’s correlation coefficient was employed to evaluate the correlation between systolic blood pressure (SBP), diastolic blood pressure (DBP) and lipid profiles. Multivariate logistic regression was performed to estimate the relationship between different lipid levels and the prevalence of hypertension. Odds ratios (ORs) and 95% confidence intervals (CIs) indicated the risk of lipid and hypertension. Bayesian model (BN) model was constructed to further assess the relationship between baseline characteristics and the prevalence of hypertension, as well as the importance of each variable for the prevalence of hypertension. Results: Compared to the non-hypertensive population, the hypertensive population was older, and had the higher body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), serum creatinine (Scr), fasting blood glucose (FPG), blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and non-high-density lipoprotein cholesterol (non-HDL-c), but HDL-c and the presence concerning the family history of diabetes were lower. Multivariate logistic regression analysis revealed that TC, LDL-c, and non-HDL-c showed a positive trend with hypertension risk (p for trend < 0.05) whereas TC and HDL-c were not significantly associated with hypertension prevalence. Moreover, each 1 mg/dl increase in TC, LDL, and non-HDL hypertension prevalence increased by 0.2% [1.002 (1.000-1.003)], 0.2% [1.002 (1.000- 1.004)], and 0.2% [1.002(1.001-1.004)], respectively. BN suggested that the importance of age, BMI, FPG, non-HDL-c on the prevalence of hypertension was 52.73%, 24.98%, 11.22%, and 2.34%, respectively. Conclusion: Overall, in Chinese adult women, TC, LDL-c and non-HDL-c levels were higher and HDL-c level was lower in the hypertensive population, whereas TG did not differ significantly from the non-hypertensive population. Meanwhile, TC, LDL-c, and non-HDL-c were positively associated with prevalence of hypertension, and HDL-c was negatively associated with prevalence of hypertension but became nonsignificant after full adjustment for variables. Moreover, BN model suggested that age, BMI, FPG, and non-HDL-c had a greater effect on the development of hypertension

Submarine groundwater discharge in Dongshan Bay, China: A master regulator of nutrients in spring and potential national significance of small bays

Despite over 90% of China’s coastal bays have an area less than 500 km2, the geochemical effects of SGD on those ecosystems are ambiguous. Based on mapping and time-series observations of Ra isotopes and nutrients, a case study of small bays (&lt;500 km2), we revealed that submarine groundwater discharge (SGD) predominately regulated the distribution of nutrients and fueled algal growth in Dongshan Bay, China. On the bay-wide scale, the SGD rate was estimated to be 0.048 ± 0.022 m day−1 and contributed over 95% of the nutrients. At the time-series site where the bay-wide highest Ra activities in the bottom water marked an SGD hotspot with an average rate an order of magnitude greater, the maximum chlorophyll concentration co-occurred, suggesting that SGD may support the algal bloom. The ever-most significant positive correlations between 228Ra and nutrients throughout the water column (P&lt; 0.01, R2 &gt; 0.90 except for soluble reactive phosphorus in the surface) suggested the predominance of SGD in controlling nutrient distribution in the bay. Extrapolated to a national scale, the SGD-carried dissolved inorganic nitrogen flux in small bays was twice as much as those in large bays (&gt;2,000 km2). Thus, the SGD-carried nutrients in small bays merit immediate attention in environmental monitoring and management

Intergenomic and epistatic interactions control free radical mediated pancreatic β-cell damage.

Alloxan (AL)-generated Reactive Oxygen Species (ROS) selectively destroy insulin-producing pancreatic β-cells. A previous genome-wide scan (GWS) using a cohort of 296 F2 hybrids between NOD (AL-sensitive) and ALR (AL-resistant) mice identified linkages contributing to β-cell susceptibility or resistance to AL-induced diabetes on Chromosomes (Chr) 2, 3, 8, and a single nucleotide polymorphism i

Efficacy and safety of PD-1/PD-L1 inhibitor-based immune combination therapy versus sorafenib in the treatment of advanced hepatocellular carcinoma: a meta-analysis

ObjectiveTo systematically evaluate the safety and efficacy of PD-1/PD-L1 inhibitor-based immunotherapy (hereafter referred to as “combination immunotherapy”) compared with that of sorafenib in the treatment of hepatocellular carcinoma (HCC).MethodsDatabases such as PubMed, Embase, and the Cochrane Library were searched from the date of their establishment to September 2023 to identify randomized controlled trials (RCTs) of combination immunotherapy versus sorafenib for the treatment of advanced HCC. Two reviewers independently evaluated the quality of the included studies, extracted the data, and cross-checked the information. The meta-analysis was performed using RevMan 5.3 software.ResultsA total of 5 RCTs were included. The results of the meta-analysis showed the following: (1) Effectiveness. Compared to sorafenib, combination immunotherapy significantly improved overall survival (OS, HR = 0.69, 95% CI: 0.58 ~ 0.82, p &lt; 0.01) and progression-free survival (PFS, HR = 0.62, 95% CI: 0.50 ~ 0.78, p &lt; 0.001) in patients with advanced HCC. (2) Safety. Both groups had comparatively high incidences of adverse events (AEs), but the difference in any treatment-related adverse events was not significant between the two arms (OR = 0.98, 95% CI: 0.95 ~ 1.02, p = 0.34). The difference in the incidence of grade 1–2 adverse reactions was statistically significant (OR = 0.66, 95% CI = 0.49–0.90, p = 0.001). There were no differences in grade 3/4 TRAEs or grade 5 TRAEs (OR = 1.46, 95% CI = 0.78 ~ 2.71, p = 0.24; OR = 1.08, 95% CI = 0.73 ~ 1.58, p = 0.71).ConclusionCombined immunotherapy can significantly prolong the OS and PFS of patients with advanced HCC without increasing the incidence of adverse effects in terms of safety, but the incidence of AEs in different systems is different

Effect of Tryptophan Hydroxylase-2 rs7305115 SNP on suicide attempts risk in major depression

<p>Abstract</p> <p>Background</p> <p>Suicide and major depressive disorders (MDD) are strongly associated, and genetic factors are responsible for at least part of the variability in suicide risk. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2) gene rs7305115 SNP may predispose to suicide attempts in MDD.</p> <p>Methods</p> <p>We genotyped TPH2 gene rs7305115 SNP in 215 MDD patients with suicide and matched MDD patients without suicide. Differences in behavioral and personality traits according to genotypic variation were investigated by logistic regression analysis.</p> <p>Results</p> <p>There were no significant differences between MDD patients with suicide and controls in genotypic (AG and GG) frequencies for rs7305115 SNP, but the distribution of AA genotype differed significantly (14.4% vs. 29.3%, <it>p </it>< 0.001). The G-allele frequency was significantly higher in cases than control group (58.1% vs.45.6%, <it>p </it>< 0.001), but the A-allele carrier indicated a decreased trend in MDD with suicide behaviors than control group (41.9% vs.54.4%, <it>p </it>< 0.001). The multivariate logistic regression analysis indicated that TPH2 rs7305115 AA (OR 0.33, 95% CI 0.22-0.99), family history of suicide (OR 2.98, 95% CI 1.17-5.04), negative life events half year ago (OR 6.64, 95% CI 2.48-11.04) and hopelessness (OR 7.68, 95% CI 5.79-13.74) were significantly associated with the suicide behaviors in MDD patients.</p> <p>Conclusions</p> <p>The study suggested that hopelessness, negative life events and family history of suicide were risk factors of attempted suicide in MDD while the TPH2 rs7305115A remained a significant protective predictor of suicide attempts.</p

Hyperglycemia Induced by Chronic Restraint Stress in Mice Is Associated With Nucleus Tractus Solitarius Injury and Not Just the Direct Effect of Glucocorticoids

Chronic restraint stress (CRS) can affect hypothalamic-pituitary-adrenal (HPA) axis activity and increase glucocorticoid levels. Glucocorticoids are stress hormones that regulate multiple aspects of energy homeostasis. Stress also impairs glucose tolerance. The aim of this study was to investigate the cause of insulin-resistant hyperglycemia during CRS. We produced the CRS models (a 7-day restraint followed by a 3-day free moving procedure, total of 4 cycles for 40 days) in mice, detected the parameters related to glucose metabolism, and compared them to those of the dexamethasone (DEX) injection (0.2 mg/kg i.p., also a 4 cycle procedure as the CRS). The results showed that the CRS induced a moderate (not higher than 11 mmol/L) and irreversible insulin-resistant hyperglycemia in about 1/3 of the individuals, and all the restrained mice had adrenal hypertrophy. CRS induced the apoptosis of neurons in the anterior part of commissural subnucleus of nucleus tractus solitarius (acNTS) in the hyperglycemic mice, and acNTS mechanical damage also led to insulin-resistant hyperglycemia. In contrast, in the DEX-treated mice, adrenal gland atrophy was evident. The glucose and insulin tolerance varied with the delay of determination. DEX exposure in vivo does not induce the apoptosis of neurons in NTS. This study indicates that restraint stress and DEX induce metabolic disorders through different mechanisms. During CRS, injury (apoptosis) of glucose-sensitive acNTS neurons cause dysregulation of blood glucose. This study also suggests the mouse restraint stress model has value as a potential application in the study of stress-induced hyperglycemia

A Genome-Wide Analysis of StTGA Genes Reveals the Critical Role in Enhanced Bacterial Wilt Tolerance in Potato During Ralstonia solanacearum Infection

TGA is one of the members of TGACG sequence-specific binding protein family, which plays a crucial role in the regulated course of hormone synthesis as a stress-responsive transcription factor (TF). Little is known, however, about its implication in response to bacterial wilt disease in potato (Solanum tuberosum) caused by Ralstonia solanacearum. Here, we performed an in silico identification and analysis of the members of the TGA family based on the whole genome data of potato. In total, 42 StTGAs were predicted to be distributed on four chromosomes in potato genome. Phylogenetic analysis showed that the proteins of StTGAs could be divided into six sub-families. We found that many of these genes have more than one exon according to the conserved motif and gene structure analysis. The heat map inferred that StTGAs are generally expressed in different tissues which are at different stages of development. Genomic collinear analysis showed that there are homologous relationships among potato, tomato, pepper, Arabidopsis, and tobacco TGA genes. Cis-element in silico analysis predicted that there may be many cis-acting elements related to abiotic and biotic stress upstream of StTGA promoter including plant hormone response elements. A representative member StTGA39 was selected to investigate the potential function of the StTGA genes for further analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) assays indicated that the expression of the StTGAs was significantly induced by R. solanacearum infection and upregulated by exogenous salicylic acid (SA), abscisic acid (ABA), gibberellin 3 (GA3), and methyl jasmonate (MeJA). The results of yeast one-hybrid (Y1H) assay showed that StTGA39 regulates S. tuberosum BRI1-associated receptor kinase 1 (StBAK1) expression. Thus, our study provides a theoretical basis for further research of the molecular mechanism of the StTGA gene of potato tolerance to bacterial wilt

Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis

Colorectal cancer (CRC) metastasizes mainly to the liver, which accounts for the majority of CRC-related deaths. Here it is shown that metastatic cells undergo specific chromatin remodeling in the liver. Hepatic growth factor (HGF) induces phosphorylation of PU.1, a pioneer factor, which in turn binds and opens chromatin regions of downstream effector genes. PU.1 increases histone acetylation at the DPP4 locus. Precise epigenetic silencing by CRISPR/dCas9KRAB or CRISPR/dCas9HDAC revealed that individual PU.1-remodeled regulatory elements collectively modulate DPP4 expression and liver metastasis growth. Genetic silencing or pharmacological inhibition of each factor along this chromatin remodeling axis strongly suppressed liver metastasis. Therefore, microenvironment-induced epimutation is an important mechanism for metastatic tumor cells to grow in their new niche. This study presents a potential strategy to target chromatin remodeling in metastatic cancer and the promise of repurposing drugs to treat metastasis

Immunosuppressive potential of human amnion epithelial cells in the treatment of experimental autoimmune encephalomyelitis

BACKGROUND: Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). In recent years, it has been found that cells such as human amnion epithelial cells (hAECs) have the ability to modulate immune responses in vitro and in vivo and can differentiate into multiple cell lineages. Accordingly, we investigated the immunoregulatory effects of hAECs as a potential therapy in an MS-like disease, EAE (experimental autoimmune encephalomyelitis), in mice. METHODS: Using flow cytometry, the phenotypic profile of hAECs from different donors was assessed. The immunomodulatory properties of hAECs were examined in vitro using antigen-specific and one-way mixed lymphocyte proliferation assays. The therapeutic efficacy of hAECs was examined using a relapsing-remitting model of EAE in NOD/Lt mice. T cell responsiveness, cytokine secretion, T regulatory, and T helper cell phenotype were determined in the peripheral lymphoid organs and CNS of these animals. RESULTS: In vitro, hAECs suppressed both specific and non-specific T cell proliferation, decreased pro-inflammatory cytokine production, and inhibited the activation of stimulated T cells. Furthermore, T cells retained their naïve phenotype when co-cultured with hAECs. In vivo studies revealed that hAECs not only suppressed the development of EAE but also prevented disease relapse in these mice. T cell responses and production of the pro-inflammatory cytokine interleukin (IL)-17A were reduced in hAEC-treated mice, and this was coupled with a significant increase in the number of peripheral T regulatory cells and naïve CD4+ T cells. Furthermore, increased proportions of Th2 cells in the peripheral lymphoid organs and within the CNS were observed. CONCLUSION: The therapeutic effect of hAECs is in part mediated by inducing an anti-inflammatory response within the CNS, demonstrating that hAECs hold promise for the treatment of autoimmune diseases like MS