Age-Related Loss of Innate Immune Antimicrobial Function of Dermal Fat Is Mediated by Transforming Growth Factor Beta.

Dermal fibroblasts (dFBs) resist infection by locally differentiating into adipocytes and producing cathelicidin antimicrobial peptide in response to Staphylococcus aureus (S. aureus). Here, we show that neonatal skin was enriched with adipogenic dFBs and immature dermal fat that highly expressed cathelicidin. The pool of adipogenic and antimicrobial dFBs declined after birth, leading to an age-dependent loss of dermal fat and a decrease in adipogenesis and cathelidicin production in response to infection. Transforming growth factor beta (TGF-ß), which acted on uncommitted embryonic and adult dFBs and inhibited their adipogenic and antimicrobial function, was identified as a key upstream regulator of this process. Furthermore, inhibition of the TGF-ß receptor restored the adipogenic and antimicrobial function of dFBs in culture and increased resistance of adult mice to S. aureus infection. These results provide insight into changes that occur in the skin innate immune system between the perinatal and adult periods of life.

Obesity alters pathology and treatment response in inflammatory disease.

Decades of work have elucidated cytokine signalling and transcriptional pathways that control T cell differentiation and have led the way to targeted biologic therapies that are effective in a range of autoimmune, allergic and inflammatory diseases. Recent evidence indicates that obesity and metabolic disease can also influence the immune system1-7, although the mechanisms and effects on immunotherapy outcomes remain largely unknown. Here, using two models of atopic dermatitis, we show that lean and obese mice mount markedly different immune responses. Obesity converted the classical type 2 T helper (TH2)-predominant disease associated with atopic dermatitis to a more severe disease with prominent TH17 inflammation. We also observed divergent responses to biologic therapies targeting TH2 cytokines, which robustly protected lean mice but exacerbated disease in obese mice. Single-cell RNA sequencing coupled with genome-wide binding analyses revealed decreased activity of nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) in TH2 cells from obese mice relative to lean mice. Conditional ablation of PPARγ in T cells revealed that PPARγ is required to focus the in vivo TH response towards a TH2-predominant state and prevent aberrant non-TH2 inflammation. Treatment of obese mice with a small-molecule PPARγ agonist limited development of TH17 pathology and unlocked therapeutic responsiveness to targeted anti-TH2 biologic therapies. These studies reveal the effects of obesity on immunological disease and suggest a precision medicine approach to target the immune dysregulation caused by obesity.

Antimicrobial peptide-producing dermal preadipocytes defend against Candida albicans skin infection via the FGFR-MEK-ERK pathway.

Dermal fibroblasts (dFBs) defend against deep bacterial skin infections by differentiating into preadipocytes (pAds) that produce the antimicrobial peptide cathelicidin; this differentiation is known as the dermal reactive adipogenesis response. However, the role of dFBs in fungal infection remains unknown. Here, we found that cathelicidin-producing pAds were present in high numbers in skin lesions from patients with cutaneous Candida granulomas. Second, we showed that dermal Candida albicans (C. albicans) infection in mice robustly triggered the dermal reactive adipogenesis response and induced cathelicidin expression, and inhibition of adipogenesis with pharmacological inhibitors of peroxisome proliferator-activated receptor γ (PPARγ) impaired skin resistance to C. albicans. In vitro, C. albicans products induced cathelicidin expression in pAds, and differentiating pAds markedly suppressed the growth of C. albicans by producing cathelicidin. Finally, we showed that C. albicans induced an antimicrobial response in pAds through the FGFR-MEK-ERK pathway. Together, our data reveal a previously unknown role of dFBs in the defense against skin infection caused by C. albicans.

Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-ß Production by Epidermal Keratinocytes during Skin Injury.

Type 1 interferons (IFNs) promote inflammation in the skin but the mechanisms responsible for inducing these cytokines are not well understood. We found that IFN-ß was abundantly produced by epidermal keratinocytes (KCs) in psoriasis and during wound repair. KC IFN-ß production depended on stimulation of mitochondrial antiviral-signaling protein (MAVS) by the antimicrobial peptide LL37 and double stranded-RNA released from necrotic cells. MAVS activated downstream TBK1 (TANK-Binding Kinase 1)-AKT (AKT serine/threonine kinase 1)-IRF3 (interferon regulatory factor 3) signaling cascade leading to IFN-ß production and then promoted maturation of dendritic cells. In mice, the production of epidermal IFN-ß by LL37 required MAVS, and human wounded and/or psoriatic skin showed activation of MAVS-associated IRF3 and induction of MAVS and IFN-ß gene signatures. These findings show that KCs are an important source of IFN-ß and MAVS is critical to this function, and demonstrates how the epidermis triggers unwanted skin inflammation under disease conditions.

Extraordinary long-stem confers resistance of intrinsic terminators to processive antitermination.

Many prokaryotic operons encode a processive antitermination (P-AT) system. Transcription complexes associated with an antitermination factor can bypass multiple transcription termination signals regardless of their sequences. However, to avoid compromising transcriptional regulation of downstream regions, the terminator at the end of the operon needs to be resistant to antitermination. So far, no studies on the mechanism of resistance to antitermination have been reported. The recently discovered conAn P-AT system is composed of two components that are encoded at the start of many conjugation operons on plasmids of Gram-positive bacteria. Here we report the identification of a conAn-resistant terminator, named TerR, in the conjugation operon of the Bacillus subtilis plasmid pLS20, re-defining the end of the conjugation operon. We investigated the various characteristics of TerR and show that its extraordinary long stem is the determining feature for resistance to antitermination. This is the first P-AT resistance mechanism to be reported.

Chromosome remodelling by SMC/Condensin in B. subtilis is regulated by monomeric Soj/ParA during growth and sporulation.

SMC complexes, loaded at ParB-parS sites, are key mediators of chromosome organization in bacteria. ParA/Soj proteins interact with ParB/Spo0J in a pathway involving adenosine triphosphate (ATP)-dependent dimerization and DNA binding, facilitating chromosome segregation in bacteria. In Bacillus subtilis, ParA/Soj also regulates DNA replication initiation and along with ParB/Spo0J is involved in cell cycle changes during endospore formation. The first morphological stage in sporulation is the formation of an elongated chromosome structure called an axial filament. Here, we show that a major redistribution of SMC complexes drives axial filament formation in a process regulated by ParA/Soj. Furthermore, and unexpectedly, this regulation is dependent on monomeric forms of ParA/Soj that cannot bind DNA or hydrolyze ATP. These results reveal additional roles for ParA/Soj proteins in the regulation of SMC dynamics in bacteria and yet further complexity in the web of interactions involving chromosome replication, segregation and organization, controlled by ParAB and SMC.

Dermal extracellular matrix molecules in skin development, homeostasis, wound regeneration and diseases.

The extracellular matrix (ECM) is a dynamic structure that surrounds and anchors cellular components in tissues. In addition to functioning as a structural scaffold for cellular components, ECMs also regulate diverse biological functions, including cell adhesion, proliferation, differentiation, migration, cell-cell interactions, and intracellular signaling events. Dermal fibroblasts (dFBs), the major cellular source of skin ECM, develop from a common embryonic precursor to the highly heterogeneous subpopulations during development and adulthood. Upon injury, dFBs migrate into wound granulation tissue and transdifferentiate into myofibroblasts, which play a critical role in wound contraction and dermal ECM regeneration and deposition. In this review, we describe the plasticity of dFBs during development and wound healing and how various dFB-derived ECM molecules, including collagen, proteoglycans, glycosaminoglycans, fibrillins and matricellular proteins are expressed and regulated, and in turn how these ECM molecules play a role in regulating the function of dFBs and immune cells. Finally, we describe how dysregulation of ECM matrix is associated the pathogenesis of wound healing related skin diseases, including chronic wounds and keloid.

Photon blockade induced by two-photon absorption in cavity quantum electrodynamics.

Photon blockade (PB) is an important quantum phenomenon in cavity quantum electrodynamics (QED). Here, we investigate the PB effect in the simplest cavity QED systems (one cavity containing first a single atom and then two atoms), where only the atoms are weakly driven. Via the analytical calculation and numerical simulation, we show that the strong PB can be generated even with the weak-coupling regime at the total resonance. This blockade is ascribed to the two-photon absorption, which is fundamentally different from the conventional and unconventional blockade mechanisms. Therefore, our study provides an alternative approach to produce the PB in the atom-driven cavity QED system.

Two new Nb-oxide indole alkaloids with ß-hematin inhibitory activity from the stems and leaves of Rauvolfia dichotoma.

Rauvolfia dichotoma, a shrub of Apocynaceae, was collected from the Islands of SAO Tome and Principe and cultivated locally for medicinal purpose. Phytochemical investigation of 95% ethanol extract from the stems and leaves of R. dichotoma led to the isolation of two new Nb-oxide indole alkaloids, namely Nb-oxide-mitoridine (1) and Nb-oxide-raucaffricine (2), together with two known alkaloids (3-4) and eleven known lignans (5-15). Their chemical structures were elucidated by extensive NMR and HR-ESI-MS data analysis. All compounds (except 13) were tested for their ß-hematin inhibitory activity. Compounds 2, 4, 14, and 15 showed certain inhibitory activity, indicating that they may have an antimalarial effect.

Exploring the mechanism of Si-Miao-Yong-An decoction on heart failure based on molecular docking and network pharmacology.

The SwissTargetPrediction was employed to predict the potential drug targets of the active component of Si-Miao-Yong-An decoction (SMYAD). The therapeutic targets for HF were searched in the Genecard database, and Cytoscape3.9.1 software was used to construct the "drug-component-target-disease network" diagram. In addition, the String platform was used to construct Protein-Protein Interaction (PPI) network, and the DAVID database was used for GO and KEGG analysis. AutoDockTools-1.5.6 software was used for molecular docking verification. Network pharmacology studies have shown that AKT 1, ALB, and CASP 3 are the key targets of action of SMYAD against heart failure. The active compounds are quercetin and kaempferol.

lncRNA ANRIL accelerates wound healing in diabetic foot ulcers via modulating HIF1A/VEGFA signaling through interacting with FUS.

BACKGROUND: Diabetic foot ulcer (DFU) is a frequently diagnosed complication of diabetes, and remains a heathcare burden worldwide. However, the pathogenesis of DFU is still largely unclear. The objective of this study is to delineate the function and underlying mechanism of lncRNA antisense non coding RNA in the INK4 locus (ANRIL) in endothelial progenitor cells (EPCs) and DFU mice. METHODS: The DFU mouse model was established, and EPCs were subjected to high glucose (HG) treatment to mimic diabetes. qRT-PCR or western blot was employed to detected the expression of ANRIL, HIF1A, FUS and VEGFA. CCK-8 and Annexin V/PI staining were used to monitor cell proliferation and apoptosis. Wound healing, Transwell invasion and tube formation assays were conducted to assess cell migration, invasion and angiogenesis, respectively. The association between ANRIL and FUS was verified by RNA pull-down and RIP assays. Luciferase and ChIP assays were employed to investigate HIF1A-mediated transcriptional regulation of VEGFA and ANRIL. The histological alterations of DFU wound healing were observed by H&E and Masson staining. RESULTS: ANRIL was downregulated in peripheral blood samples of DFU patients, DFU mice and HG-treated EPCs. Mechanistically, ANRIL regulated HIFA mRNA stability via recruiting FUS. VEGFA and ANRIL were transcriptionally regulated by HIF1A. Functional experiments revealed that HG suppressed EPC proliferation, migration, invasion and tube formation, but promoted apoptosis via ANRIL/HIF1A axis. ANRIL accelerated DFU wound healing via modulating HIF1A expression in vivo. CONCLUSION: ANRIL accelerated wound healing in DFU via modulating HIF1A/VEGFA signaling in a FUS-dependent manner.

Alteriqipengyuania flavescens sp. nov., isolated from Pearl River Estuary sediment.

Two Gram-stain-negative, aerobic, rod-shaped, non-motile and golden yellow pigmented bacteria, designated as SCSIO 75105T and SCSIO 75732, were isolated from sediment in the Pearl River Estuary, Guangdong Province, PR China. Cells were positive for catalase and oxidase. Growth occurred at 10-37 °C (optimum, 28 °C), pH 6.0-10.0 (optimum, pH 7.0) and 0-5.0 % (w/v) NaCl (optimum, 2.0-3.0 %). The 16S rRNA gene analysis indicated that these two isolates shared a similarity of 100 % each other. The 16S rRNA gene sequence analysis indicated that these two isolates showed highest similarity to Altererythrobacter ishigakiensis CGMCC 1.14979T (97.3 %). However, a phylogenetic tree based on 288 orthologous clusters indicated that these two isolates were closely related to Alteriqipengyuania halimionae CPA5T. The average nucleotide identity, average amino acid identity, digital DNA-DNA hybridization and evolutionary distance values between the two isolates and Alteriqipengyuania halimionae CPA5T were 73.7-74.0 %, 65.2 %, 19.5 % and 0.24, respectively. The genomic DNA G+C content of both isolates was 65.2 mol%. The major cellular fatty acids were C18 : 1 ω7c, C17 : 1 ω6c and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), and Q-10 was the respiratory quinone. The polar lipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, sphingoglycolipid and one unidentified glycolipid. On the basis of the results of phenotypic, physiological, chemotaxonomic and genotypic characterization, strains SCSIO 75105T and SCSIO 75732 are considered to represent a novel species in the genus Alteriqipengyuania, for which the name Alteriqipengyuania flavescens sp. nov. is proposed. The type strain is SCSIO 75105T (=KCTC 92502T=MCCC 1K07993T).

Seagrass Thalassia hemprichii and associated bacteria co-response to the synergistic stress of ocean warming and ocean acidification.

Seagrass meadows play vital ecological roles in the marine ecosystem. Global climate change poses considerable threats to seagrass survival. However, it is unclear how seagrass and its associated bacteria will respond under future complex climate change scenarios. This study explored the effects of ocean warming (+2 °C) and ocean acidification (-0.4 units) on seagrass physiological indexes and bacterial communities (sediment and rhizosphere bacteria) of the seagrass Thalassia hemprichii during an experimental exposure of 30 days. Results demonstrated that the synergistic effect of ocean warming and ocean acidification differed from that of one single factor on seagrass and the associated bacterial community. The seagrass showed a weak resistance to ocean warming and ocean acidification, which manifested through the increase in the activity of typical oxidoreductase enzymes. Moreover, the synergistic effect of ocean warming and ocean acidification caused a significant decrease in seagrass's chlorophyll content. Although the bacterial community diversity exhibited higher resistance to ocean warming and ocean acidification, further bacterial functional analysis revealed the synergistic effect of ocean warming and ocean acidification led to significant increases in SOX-related genes abundance which potentially supported the seagrass in resisting climate stress by producing sulfates and oxidizing hydrogen sulfide. More stable bacterial communities were detected in the seagrass rhizosphere under combined ocean warming and ocean acidification. While for one single environmental stress, simpler networks were detected in the rhizosphere. In addition, the observed significant correlations between several modules of the bacterial community and the physiological indexes of the seagrass indicate the possible intimate interaction between seagrass and bacteria under ocean warming and ocean acidification. This study extends our understanding regarding the role of seagrass associated bacterial communities and sheds light on both the prediction and preservation of the seagrass meadow ecosystems in response to global climate change.

A novel bipartite antitermination system widespread in conjugative elements of Gram-positive bacteria.

Transcriptional regulation allows adaptive and coordinated gene expression, and is essential for life. Processive antitermination systems alter the transcription elongation complex to allow the RNA polymerase to read through multiple terminators in an operon. Here, we describe the discovery of a novel bipartite antitermination system that is widespread among conjugative elements from Gram-positive bacteria, which we named conAn. This system is composed of a large RNA element that exerts antitermination, and a protein that functions as a processivity factor. Besides allowing coordinated expression of very long operons, we show that these systems allow differential expression of genes within an operon, and probably contribute to strict regulation of the conjugation genes by minimizing the effects of spurious transcription. Mechanistic features of the conAn system are likely to decisively influence its host range, with important implications for the spread of antibiotic resistance and virulence genes.

Lecanicilliums A-F, Thiodiketopiperazine-Class Alkaloids from a Mangrove Sediment-Derived Fungus Lecanicillium kalimantanense.

Six new thiodiketopiperazine-class alkaloids lecanicilliums A-F were isolated from the mangrove sediment-derived fungus Lecanicillium kalimantanense SCSIO41702, together with thirteen known analogues. Their structures were determined by spectroscopic analysis. The absolute configurations were determined by quantum chemical calculations. Electronic circular dichroism (ECD) spectra and the structure of Lecanicillium C were further confirmed by a single-crystal X-ray diffraction analysis. Lecanicillium A contained an unprecedented 6/5/6/5/7/6 cyclic system with a spirocyclic center at C-2'. Biologically, lecanicillium E, emethacin B, and versicolor A displayed significant cytotoxicity against human lung adenocarcinoma cell line H1975, with IC50 values of 7.2~16.9 µM, and lecanicillium E also showed antibacterial activity against four pathogens with MIC values of 10~40 µg/mL. Their structure-activity relationship is also discussed.

Evaluation of the Different Nutritional and Environmental Parameters on Microbial Pyrene Degradation by Mangrove Culturable Bacteria.

Mangrove ecosystems play curial roles in providing many ecological services and alleviating global climate change. However, they are in decline globally, mainly threatened by human activities and global warming, and organic pollutants, especially PAHs, are among the crucial reasons. Microbial remediation is a cost-effective and environmentally friendly way of alleviating PAH contamination. Therefore, understanding the effects of environmental and nutritional parameters on the biodegradation of polycyclic aromatic hydrocarbons (PAHs) is significant for the bioremediation of PAH contamination. In the present study, five bacterial strains, designated as Bp1 (Genus Rhodococcus), Sp8 (Genus Nitratireductor), Sp13 (Genus Marinobacter), Sp23 (Genus Pseudonocardia), and Sp24 (Genus Mycolicibacterium), have been isolated from mangrove sediment and their ring hydroxylating dioxygenase (RHD) genes have been successfully amplified. Afterward, their degradation abilities were comprehensively evaluated under normal cultural (monoculture and co-culture) and different nutritional (tryptone, yeast extract, peptone, glucose, sucrose, and NPK fertilizer) and environmental (cetyl trimethyl ammonium bromide (CTAB), sodium dodecyl sulfate (SDS)) parameters, as well with different co-contaminants (phenanthrene and naphthalene) and heavy metals (Cd2+, Cu2+, Fe3+, Ni2+, Mg2+, Mn2+, and Co2+). The results showed that strain Sp24 had the highest pyrene degradation rate (85%) in the monoculture experiment after being cultured for 15 days. Adding nitrogen- and carbon-rich sources, including tryptone, peptone, and yeast extract, generally endorsed pyrene degradation. In contrast, the effects of carbon sources (glucose and sucrose) on pyrene degradation were distinct for different bacterial strains. Furthermore, the addition of NPK fertilizer, SDS, Tween-80, phenanthrene, and naphthalene enhanced the bacterial abilities of pyrene removal significantly (p < 0.05). Heavy metals significantly reduced all bacterial isolates' degradation potentials (p < 0.05). The bacterial consortia containing high bio-surfactant-producing strains showed substantially higher pyrene degradation. Moreover, the consortia of three and five bacterial strains showed more degradation efficiency than those of two bacterial strains. These results provide helpful microbial resources for mangrove ecological remediation and insight into optimized culture strategies for the microbial degradation of PAHs.

Coordinated Patient Care via Mobile Phone-Based Telemedicine in Secondary Stroke Prevention: A Propensity Score-Matched Cohort Study.

BACKGROUND: To prevent recurrent stroke, patients need to follow evidence-based practices following discharge; however, adherence to these practices is suboptimal. PURPOSE: To evaluate whether a smartphone mobile application can improve medication adherence and stroke awareness in secondary stroke prevention. METHODS: A retrospective study design was used. Patients with ischemic stroke registered in a database between August 2018 and January 2019 were enrolled. Propensity score matching was used to match patients managed with the mobile application compared with regular practice in a 1:2 ratio. RESULTS: Sixty-five patients were paired with 123 controls. Three-month medication adherence was 93.8% in the application group versus 82.9% in the control group ( P = .036). Patients in the application group were more likely to know stroke warning signs ( P = .003) and when to call an ambulance for stroke symptoms (87.7% vs 72.4%, P = .016). CONCLUSIONS: Using a mobile application may increase medication adherence and stroke awareness in secondary stroke prevention.

[Associations Between Insulin Resistance Indexes and Hyperuricemia in Hypertensive Population].

Objective To explore the relationship between insulin resistance (IR) indexes and hyperuricemia (HUA) among the people with hypertension. Methods From July to August in 2018,hypertension screening was carried out in Wuyuan county,Jiangxi province,and the data were collected through questionnaire survey,physical measurement,and biochemical test.Logistic regression was performed to analyze the relationship between HUA and IR indexes including metabolic score for IR (METS-IR),triglyceride-glucose (TyG) index,TyG-body mass index (BMI),TyG-waist circumference (WC),visceral adiposity index (VAI),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and lipid accumulation product (LAP).The penalty spline method was used for the curve fitting between IR indexes and HUA.The area under the receiver operating characteristic curve (AUC) was employed to reveal the correlation between each index and HUA. Results The 14 220 hypertension patients included 6 713 males and 7 507 females,with the average age of (63.8±9.4) years old,the average uric acid level of (418.9±120.6) mmol/L,and the HUA detection rate of 44.4%.The HUA group had higher proportions of males,current drinking,current smoking,diabetes,and using antihypertensive drugs,older age,higher diastolic blood pressure,WC,BMI,homocysteine,total cholesterol,TG,low-density lipoprotein cholesterol,blood urea nitrogen,creatinine,aspartate aminotransferase,alanine aminotransferase,total protein,albumin,total bilirubin,direct bilirubin, METS-IR, TyG, TyG-BMI, TyG-WC, VAI, TG/HDL-C, and LAP, and lower systolic blood pressure and HDL-C than the normal uric acid group (all P<0.05).Multivariate Logistic regression showed that METS-IR (OR=1.049,95%CI=1.038-1.060, P<0.001), TyG (OR=1.639,95%CI=1.496-1.797, P<0.001), TyG-BMI (OR=1.008,95%CI=1.006-1.010, P<0.001), TyG-WC (OR=1.003,95%CI=1.002-1.004, P<0.001), lnVAI (OR=1.850, 95%CI=1.735-1.973, P<0.001), ln(TG/HDL-C) (OR=1.862,95%CI=1.692-2.048, P<0.001),and lnLAP (OR=1.503,95%CI=1.401-1.613,P<0.001) were associated with the risk of HUA.Curve fitting indicated that METS-IR,TyG,TYG-BMI,TYG-WC,lnVAI,ln(TG/HDL-C),and lnLAP were positively correlated with HUA (all P<0.001),and the AUC of TyG index was higher than that of other IR indexes (all P<0.05). Conclusion Increased IR indexes,especially TyG,were associated with the risk of HUA among people with hypertension.

[Predictive Effects of Different Insulin Resistance Indexes on Diabetes Risk in Hypertensive Population].

Objective To explore the roles of different insulin resistance indexes[triglyceride-glucose (TyG),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and metabolic score for insulin resistance (METS-IR)]and combinations of two indexes in predicting diabetes risk in hypertensive population. Methods The survey of hypertension was conducted for the residents in Wuyuan county,Jiangxi province from March to August in 2018.The basic information of hypertensive residents was collected by interview.Blood was drawn on an empty stomach in the morning and physical measurements were carried out.Logistic regression model was employed to analyze the relationship between different insulin resistance indexes and diabetes,and the area under the receiver operating characteristic curve was used for evaluating the predictive effects of each index on diabetes risk. Results A total of 14 222 hypertensive patients with an average age of (63.8±9.4) years old were included in this study,including 2616 diabetic patients.The diabetic hypertensive population had higher TyG (t=50.323,P<0.001),TG/HDL-C (Z=17.325,P<0.001),and METS-IR (t=28.839,P<0.001) than the non-diabetic hypertensive population.Multivariate analysis showed that each insulin resistance index was positively correlated with diabetes risk.The area under curve of each insulin index was in a descending order of TyG (0.770)> METS-IR (0.673)> TG/HDL-C (0.620).The difference in the area under curve between two indexes was statistically significant[TyG vs.TG/HDL-C (Z=42.325,P<0.001);TyG vs.METS-IR(Z=17.517,P<0.001);METS-IR vs.TG/HDL-C (Z=10.502,P<0.001)]. Conclusions Elevated insulin resistance indexes can increase the risk of diabetes.TyG and the combination of indexes outperform TG/HDL-C and METS-IR in the prediction of diabetes.

[Relationship of Cognitive Function With Menarche Age,Menopause Age, and Reproductive Period in Female Patients With Hypertension].

Objective To explore the relationship of menarche age,menopause age,and reproductive period with cognitive function in the female patients with hypertension.Methods Hypertension screening was carried out in Wuyuan county of Jiangxi province from July to August in 2018.Data were collected through a face-to-face questionnaire survey,physical measurement,and biochemical tests.The cognitive function was scored according to the mini-mental state examination(MMSE)scale.Multiple linear regression and Logistic regression were employed to analyze the effects of menarche age,menopause age,and reproductive period on cognitive function,and the penalized spline regression to fit the curves.Results A total of 4595 postmenopausal women with hypertension were included in the analysis,with the mean age of(65.1±8.4)years,mean menarche age of(16.6±2.2)years,mean menopause age of(48.2±5.0)years,mean reproductive period of(31.7±5.5)years,mean MMSE score of(19.0±6.3)points,and total cognitive impairment detection rate of 40.4%(1859/4595).The detection rates of cognitive impairment were 28.4%,39.1%,and 45.8% in the females with the menarche ages of <15,15-16,and ≥17 years,47.9%,39.7%,and 38.3% in the females with the menopausal ages of <45,45-49,and ≥50 years,and 56.0%,44.4%,40.6%,and 32.6% in the females with the reproductive periods of <25,25-29,30-34,and ≥35 years,respectively.Moreover,the detection rates of cognitive impairment among different age groups were statistically significant(all P<0.05).Compared with the group with the menarche age <15 years,the groups with the menarche ages of 15-16 years and ≥17 years showed increased detection rates of cognitive impairment(OR=1.45,95%CI=1.19-1.75,P<0.001;OR=1.65,95%CI=1.37-1.98,P<0.001).Compared with the group with the menopausal age <45 years,the groups with the menopausal ages of 45-49 years and ≥50 years showed decreased detection rates of cognitive impairment(OR=0.80,95%CI=0.66-0.95,P=0.013;OR=0.78,95%CI=0.65-0.93,P<0.001).Compared with the group with the reproductive period <25 years,the groups with the reproductive periods of 25-29,30-34,and ≥35 years showed decreased detection rates of cognitive impairment(OR=0.66,95%CI=0.52-0.84,P<0.001;OR=0.62,95%CI=0.50-0.76,P<0.001;OR=0.51,95%CI=0.41-0.63,P<0.001).Conclusion The detection rate of cognitive impairment had a positive correlation with menarche age and negative correlations with menopause age and reproductive period in the female patients with hypertension.