A simulation study on the antiarrhythmic mechanisms of established agents in myocardial ischemia and infarction.

Patients with myocardial ischemia and infarction are at increased risk of arrhythmias, which in turn, can exacerbate the overall risk of mortality. Despite the observed reduction in recurrent arrhythmias through antiarrhythmic drug therapy, the precise mechanisms underlying their effectiveness in treating ischemic heart disease remain unclear. Moreover, there is a lack of specialized drugs designed explicitly for the treatment of myocardial ischemic arrhythmia. This study employs an electrophysiological simulation approach to investigate the potential antiarrhythmic effects and underlying mechanisms of various pharmacological agents in the context of ischemia and myocardial infarction (MI). Based on physiological experimental data, computational models are developed to simulate the effects of a series of pharmacological agents (amiodarone, telmisartan, E-4031, chromanol 293B, and glibenclamide) on cellular electrophysiology and utilized to further evaluate their antiarrhythmic effectiveness during ischemia. On 2D and 3D tissues with multiple pathological conditions, the simulation results indicate that the antiarrhythmic effect of glibenclamide is primarily attributed to the suppression of efflux of potassium ion to facilitate the restitution of [K+]o, as opposed to recovery of IKATP during myocardial ischemia. This discovery implies that, during acute cardiac ischemia, pro-arrhythmogenic alterations in cardiac tissue's excitability and conduction properties are more significantly influenced by electrophysiological changes in the depolarization rate, as opposed to variations in the action potential duration (APD). These findings offer specific insights into potentially effective targets for investigating ischemic arrhythmias, providing significant guidance for clinical interventions in acute coronary syndrome.

Single-cell RNA sequencing reveals tumor heterogeneity within salivary gland pleomorphic adenoma: A preliminary study.

BACKGROUND: Salivary gland pleomorphic adenoma (SPA) is a common neoplasm of salivary glands that displays remarkable histological diversity. Previous studies have demonstrated the involvement of gene rearrangements and cytoskeleton-remodeling-related myoepithelial cells in SPA tumorigenesis. Cytoskeleton remodeling is necessary for epithelial-mesenchymal transition (EMT), a key process in tumor progression. However, the heterogeneity of tumor cells and cytoskeleton remodeling in SPA has not been extensively investigated. METHODS: An analysis of single-cell RNA sequencing (scRNA-seq) was performed on 27 810 cells from two donors with SPA. Bioinformatic tools were used to assess differentially expressed genes, cell trajectories, and intercellular communications. Immunohistochemistry and double immunofluorescence staining were used to demonstrate FOXC1 and MYLK expression in SPA tissues. RESULTS: Our analysis revealed five distinct cell subtypes within the tumor cells of SPA, indicating a high level of intra-lesional heterogeneity. Cytoskeleton-remodeling-related genes were highly enriched in subtype 3 of the tumor cells, which showed a close interaction with mesenchymal cells. We found that tumoral FOXC1 expression was closely related to MYLK expression in the tumor cells of SPA. CONCLUSION: Tumor cells enriched with cytoskeleton-remodeling-related genes play a crucial role in SPA development, and FOXC1 may partially regulate this process.

Long Non-Coding RNA Dancr Affects Myocardial Fibrosis in Atrial Fibrillation Mice via the MicroRNA-146b-5p/Smad5 Axis.

Objectives: Atrial fibrillation (AF) is the most frequent arrhythmia, and myocardial fibrosis (MF) has a close association with atrial remodeling and leads to AF. This study aimed to explore the function of the long non-coding RNA (lncRNA) differentiation antagonizing non-protein coding RNA (Dancr)/microRNA (miR)-146b-5p/Smad5 axis on MF in AF mice. Methods: AF mouse models were established. Overexpression Dancr lentivirus was injected into AF mice to increase Dancr expression in myocardial tissues. LncRNA Dancr, miR-146b-5p, and Smad5 expression levels and inflammatory factors (IL-18 and TNF-α) in the myocardial tissues were measured. MF was measured and the expression levels of MF-related genes (COL1A1, α-SMA, and FN1) were detected. In addition, in vitro HL-1 cell rapid pacing models were constructed, and after lncRNA Dancr and miR-146b-5p-related construct transfection, cell viability and cell apoptosis were determined. Results: LncRNA Dancr up-regulation ameliorated MF in the AF mice, reduced IL-18 and TNF-α expression levels in myocardial tissues, and decreased COL1A1, α-SMA, and FN1 expression levels. The in vitro HL-1 cell rapid pacing models suggested that miR-146b-5p overexpression reversed the inhibitory effects of lncRNA Dancr overexpression on MF in HL-1 cells, and Smad5 interference reversed the ameliorative effects of miR-146b-5p interference on MF in HL-1 cells. Conclusions: LncRNA Dancr can sponge miR-146b-5p to promote Smad5 expression, thereby delaying MF in AF mice.

Phthalocyanine-Triggered Helical Dipeptide Nanotubes with Intense Circularly Polarized Luminescence.

Nanotubes with circularly polarized luminescence (CPL) are attracting much attention due to many potential applications, such as chiroptical materials, displays, and sensing. However, it remains a challenge to change the assemblies of ordinarily molecular building blocks into CPL supramolecular nanotubes. Herein, the regulation of quite common dipeptide (Fmoc-FF) assemblies into unprecedented helical nanotubes exhibiting intense CPL is reported by simply doping a few phthalocyanine (octakis(carboxyl)phthalocyaninato zinc complex (Pc)) molecules. Interestingly, altering the Fmoc-FF/Pc molar ratios over a wide range cannot change the nanotubes structures according to transmission electron microscopy (TEM) and atomic force microscope (AFM) measurements. Although molecular dynamics simulations suggest that the noncovalent interactions between Fmoc-FF and Pc are quite weak, few Pc molecules can still change the secondary structures of a large number of Fmoc-FF assemblies, which hierarchically form helical supramolecular nanotubes with long-range ordered molecular packing, leading to intense CPL signals with large luminescence dissymmetry factor (glum  = 0.04). Consequently, the chiral reorganization of Fmoc-FF assemblies is dependent on the coassembly between Pc molecule and Fmoc-FF supramolecular architectures. These results open the possibility for the fine-tuning of helix and supramolecular nanotubes with CPL properties by using a small number of cofactors.

Room temperature chiral reorganization of interfacial assembly of achiral double-decker phthalocyanine.

The modulation of solid-state supramolecular assemblies at room temperature is still challenging even though it potentially has very important application prospects. Herein, based on the possibility of overall conformational changes in double-decker phthalocyanine, the room temperature chiral reorganization of solid-state assemblies was investigated. LS (Langmuir-Schaefer) films of achiral double-decker cerium phthalocyanine were fabricated via air-water interfacial assembly and the dependence of supramolecular chirality on the assembly of the achiral double-decker molecules was identified. Interestingly, the corresponding supramolecular chirality in the solid-state can be reorganized with amplification of the Cotton effect and formation of helical nanostructures upon storage at room temperature and atmospheric pressure. These results open new perspectives for the regulation of supramolecular assemblies.

The O-antigen structure of bacterium Comamonas aquatica CJG.

Genus Comamonas is a group of bacteria that are able to degrade a variety of environmental waste. Comamonas aquatica CJG (C. aquatica) in this genus is able to absorb low-density lipoprotein but not high-density lipoprotein of human serum. Using 1H and 13C NMR spectroscopy, we found that the O-polysaccharide (O-antigen) of this bacterium is comprised of a disaccharide repeat (O-unit) of d-glucose and 2-O-acetyl-l-rhamnose, which is shared by Serratia marcescens O6. The O-antigen gene cluster of C. aquatica, which is located between coaX and tnp4 genes, contains rhamnose synthesis genes, glycosyl and acetyl transferase genes, and ATP-binding cassette transporter genes, and therefore is consistent with the O-antigen structure determined here.

Fluorescent Phthalocyanine Assembly Distinguishes Chiral Isomers of Different Types of Amino Acids and Sugars.

The functions of some natural supramolecular architectures, such as ribosomes, are dependent on the recognition of different types of chiral biomolecules. However, the recognition of different types of chiral molecules (multiobject chiral recognition), such as amino acids and sugars, by independent and identically artificial supramolecular assembly, was rarely achieved. In this article, simple amphiphilic achiral phthalocyanine was found to form supramolecular chiral assemblies with charged water-soluble polymers upon host-guest interactions at the air/water interface. Among these systems, one identical phthalocyanine/poly(l-lysine) assembly not only can distinguish enantiomers of different amino acids but also can recognize several epimers of monose. The chiral recognitions were achieved by comparing either the steady-state fluorescence intensity or fluorescence quenching rate of phthalocyanine/poly(l-lysine) assemblies, before and after interaction with different small chiral molecules. It was demonstrated that the interactions between poly(l-lysine) and different small chiral molecules could change the aggregation of phthalocyanines. And the sensitivity of fluorescence and the excellent multiobject chiral recognition properties of the phthalocyanine/poly(l-lysine) assembly are dependent on the subtle molecular packing mode and the cooperation of different noncovalent interactions.

Syngnathia Between the Palate and Mouth Floor, Cleft Palate, and Funnel Chest.

Syngnathia is a rare malformation involving soft tissue and/or bony adhesions between the maxilla and mandible. Less than 40 patients have been reported in the literature. Here the authors report a 6-month-old infant diagnosed as syngnathia of the palate and mouth floor combined with cleft palate and funnel chest in the Department of Oral and Maxillofacial Surgery at Henan Provincial People's Hospital in January 2015. The authors discussed and evaluated the diagnostic and treatment difficulties on surgical and anesthetic procedure. There is no standard treatment protocol, but early treatment is necessary to improve airway functions and infant feeding, and to support proper nutrition for the growth of maxillofacial region.

Inhibition of Mer and Axl receptor tyrosine kinases leads to increased apoptosis and improved chemosensitivity in human neuroblastoma.

Ectopic expression of Mer and Axl receptor tyrosine kinases (RTKs) are frequently found in various cancers as known to promote oncogenesis by activating antiapoptotic signaling pathways. However, the roles of these receptors in neuroblastoma remain unclear. We found Mer and Axl was co-expressed in neuroblastoma patient samples and cell lines. Ligand-dependent Mer or Axl activation led to an increase in phosphorylated ERK1/2, AKT and FAK indicating roles for these RTKs in multiple oncogenic processes. Furthermore, Mer and Axl knockdown led to apoptosis and inhibition of migration as well as a significant increase in chemosensitivity in response to cisplatin and vincristine treatment. Taken together, our results demonstrated that inhibition of Mer and Axl improved apoptotic response and chemosensitivity in neuroblastoma, providing new insights into development of novel therapeutic strategies by targeting these oncogenes.

Drug-Coated Balloons for De Novo Coronary Artery Lesions: A Meta-Analysis of Randomized Clinical Trials.

PURPOSE: Through meta-analysis, we aimed to assess the efficacy and safety of drug-coated balloons (DCB), compared with drug-eluting stents (DES) or uncoated devices, in the treatment of de novo coronary lesions. MATERIALS AND METHODS: Only randomized controlled trials were included. The primary outcomes were late lumen loss (LLL), target lesion revascularization (TLR), and major adverse cardiac events (MACEs). Subgroup analyses were conducted based on clinical indications, whether DCBs were used with a systematic or bailout stent, and types of DESs. RESULTS: The present meta-analysis demonstrated that DCBs elicit significantly lower incidences of TLR, MACE, and LLL, compared with uncoated devices, and similar incidences, compared with DESs, in the treatment of de novo coronary lesions. Subgroup analysis indicated that DCBs used with a bailout stent achieved lower incidences of binary restenosis and myocardial infarction, compared with uncoated devices, and provided less LLL than DESs. DCBs showed similar rates of TLR and MACE, with significantly less LLL, than DESs in treating de novo small-vessel diseases. The clinical efficacy of DCBs was similar to that of second-generation DES. CONCLUSION: Overall, DCB is favored over bare metal stent alone in treating de novo coronary lesions. DCBs appear to be a promising alternative to DESs in the treatment of de novo coronary lesions.

Mandibular Reconstruction With the Contralateral Vascularized Iliac Flap Using Individual Design: Iliac Crest Used to Reconstruct the Ramus and the Anterior Border of the Iliac Wing Used to Reconstruct the Inferior Border: A Case Report.

Mandible defects resulting from resection of benign or malignant lesions, trauma, or radionecrosis are commonly encountered in the oral and maxillofacial department. Vascularized bone flaps, in general, provide the best functional and aesthetic outcome. The iliac crest provides a large piece of curved cortico-cancellous bone, measuring 6-16 cm in length. It has a natural curvature that complements the curve of the lateral and sometimes anterior mandible and can be placed accordingly to fill defects. In the paper, we report a mandibular reconstruction with a vascularized iliac flap using individual virtual preoperative planning and 3D printing technology. We want to offer a new design idea for mandibular defect reconstruction.

Comprehensive analysis of 65 patients with Castleman disease in a single center in China.

This study aimed to investigate the epidemiologic, clinical, pathological characteristics, and treatment of patients with Castleman disease (CD) in a single center in China. We retrospectively analyzed the data of 65 Chinese CD patients, divided into unicentric CD (UCD) and multicentric CD (MCD) groups, and also microscopic subtypes as hypervascular (HV), plasmacytic (PC) and Mixed. Based on whether HHV-8 infection existed, MCD was subdivided into HHV-8-associated MCD and idiopathic Castleman disease (iMCD). Detailed epidemiologic, clinicopathological, and treatment data were analyzed and discussed. Of total 65 patients (UCD 33, MCD 32), HV (81.8%) accounted for the most of UCD and total. More females in UCD (60.6%) and more males in MCD (65.6%) were observed. CD occurred in all age groups, most commonly in 40-49 years. The mean age of onset of total was 38.5 years with PC higher than HV (45.5 vs. 35.1 years, P = 0.0413). The median diagnosis delay of MCD was longer than that of UCD (3.00 vs. 1.25 months, P = 0.0436). Abdomen (39.4%) and neck (30.3%) were the most-seen locations of lymphadenopathy in UCD, with neck (65.6%) being predominant in MCD. Mean major diameter of specimens of UCD was greater than MCD (6.4 vs. 3.1 cm, P < 0.0001). These results provided the featured and detailed profile of Castleman disease in Henan province in China with a considerable number of cases, which presented distinct evidence with other studies.

Assembled small organic molecules for photodynamic therapy and photothermal therapy.

As a worldwide major public health problem, cancer is one of the leading causes of death. Effective treatment of cancer is an important challenge. Therefore, photodynamic therapy (PDT) and photothermal therapy (PTT) have been widely applied as anti-tumour strategies due to their high-performance and limited side effects. Inspired by natural supramolecular architectures, such as cytochromes and photosystems, the hierarchical supramolecular assembly of small organic molecules has been developed for their use as photosensitizers or photothermal agents for PDT and PTT, respectively. In this manuscript, we will summarize the recent progress of PDT and PTT based on the assembly of small organic molecules.

Novel Hybrid Manufacturing Process of CM247LC and Multi-Material Blisks.

The study on CM247LC used the traditional approach for Near-Netshape Hot Isostatic Pressing (NNSHIP) with sacrificial low carbon steel tooling, which was built using Selective Laser Melting (SLM), to produce a shaped CM247LC blisk. The assessment of the microstructure focused on both the exterior components in order to determine the depth of the Fe-diffusion layer and on the interior microstructure. Samples were extracted from the Hot Isostatic Pressed (HIPped) components for tensile testing at both room and elevated temperatures. The components were scanned to assess the geometrical shrinkages due to Hot Isostatic Pressing (HIPping). An oversized blisk was also produced based on the measurements as a demonstrator component. In addition, a further study was carried out on a novel idea that used a solid IN718 disk in the centre of the blisk to create a multi-material component.

Internal Jugular Vein Fenestration and Duplication: Anatomical Findings, Prevalence, and Literature Review.

Background: Comprehensive knowledge of the internal jugular vein (IJV) regarding its anatomical variations and the pattern of its course is valuable for preventing unexpected injuries during surgical procedures or central venous access. IJV anatomical anomalies such as fenestration and duplication are rare, mainly represented by case reports, and intraoperative findings. Objective: To present two additional cases of IJV anomalies and highlight its clinical presentation, anatomical characteristics, management, and prevalence through an extensive literature review. Methods and Case Reports: From January 2017 to December 2018, we retrospectively collected data of 221 patients undergoing neck dissection (ND) procedures and identified two patients with IJV anomalies (fenestration and duplication) providing a clinical prevalence of ~0.9%. The IJV fenestration referred to an IJV bifurcation that reunites proximal to the subclavian vein, whereas in the IJV duplication both branches remain separated. In both of our cases, the spinal accessory nerve (SAN) crossed the window between the IJV branches. Conclusion: Anatomical variations are more likely to be identified intraoperatively or incidentally, and due to the risk of SAN and vascular injury, special attention should be taken to identify them preoperatively in order to reduce the risk of iatrogenic injury and unexpected complications.

Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China.

BACKGROUND: Studies have reminded that cardiovascular metabolic comorbidities made patients more susceptible to suffer 2019 novel corona virus (2019-nCoV) disease (COVID-19), and exacerbated the infection. The aim of this analysis is to determine the association of cardiovascular metabolic diseases with the development of COVID-19. METHODS: A meta-analysis of eligible studies that summarized the prevalence of cardiovascular metabolic diseases in COVID-19 and compared the incidences of the comorbidities in ICU/severe and non-ICU/severe patients was performed. Embase and PubMed were searched for relevant studies. RESULTS: A total of six studies with 1527 patients were included in this analysis. The proportions of hypertension, cardia-cerebrovascular disease and diabetes in patients with COVID-19 were 17.1%, 16.4% and 9.7%, respectively. The incidences of hypertension, cardia-cerebrovascular diseases and diabetes were about twofolds, threefolds and twofolds, respectively, higher in ICU/severe cases than in their non-ICU/severe counterparts. At least 8.0% patients with COVID-19 suffered the acute cardiac injury. The incidence of acute cardiac injury was about 13 folds higher in ICU/severe patients compared with the non-ICU/severe patients. CONCLUSION: Patients with previous cardiovascular metabolic diseases may face a greater risk of developing into the severe condition and the comorbidities can also greatly affect the prognosis of the COVID-19. On the other hand, COVID-19 can, in turn, aggravate the damage to the heart.

A deep learning algorithm for detection of oral cavity squamous cell carcinoma from photographic images: A retrospective study.

BACKGROUND: The overall prognosis of oral cancer remains poor because over half of patients are diagnosed at advanced-stages. Previously reported screening and earlier detection methods for oral cancer still largely rely on health workers' clinical experience and as yet there is no established method. We aimed to develop a rapid, non-invasive, cost-effective, and easy-to-use deep learning approach for identifying oral cavity squamous cell carcinoma (OCSCC) patients using photographic images. METHODS: We developed an automated deep learning algorithm using cascaded convolutional neural networks to detect OCSCC from photographic images. We included all biopsy-proven OCSCC photographs and normal controls of 44,409 clinical images collected from 11 hospitals around China between April 12, 2006, and Nov 25, 2019. We trained the algorithm on a randomly selected part of this dataset (development dataset) and used the rest for testing (internal validation dataset). Additionally, we curated an external validation dataset comprising clinical photographs from six representative journals in the field of dentistry and oral surgery. We also compared the performance of the algorithm with that of seven oral cancer specialists on a clinical validation dataset. We used the pathological reports as gold standard for OCSCC identification. We evaluated the algorithm performance on the internal, external, and clinical validation datasets by calculating the area under the receiver operating characteristic curves (AUCs), accuracy, sensitivity, and specificity with two-sided 95% CIs. FINDINGS: 1469 intraoral photographic images were used to validate our approach. The deep learning algorithm achieved an AUC of 0·983 (95% CI 0·973-0·991), sensitivity of 94·9% (0·915-0·978), and specificity of 88·7% (0·845-0·926) on the internal validation dataset (n = 401), and an AUC of 0·935 (0·910-0·957), sensitivity of 89·6% (0·847-0·942) and specificity of 80·6% (0·757-0·853) on the external validation dataset (n = 402). For a secondary analysis on the internal validation dataset, the algorithm presented an AUC of 0·995 (0·988-0·999), sensitivity of 97·4% (0·932-1·000) and specificity of 93·5% (0·882-0·979) in detecting early-stage OCSCC. On the clinical validation dataset (n = 666), our algorithm achieved comparable performance to that of the average oral cancer expert in terms of accuracy (92·3% [0·902-0·943] vs 92.4% [0·912-0·936]), sensitivity (91·0% [0·879-0·941] vs 91·7% [0·898-0·934]), and specificity (93·5% [0·909-0·960] vs 93·1% [0·914-0·948]). The algorithm also achieved significantly better performance than that of the average medical student (accuracy of 87·0% [0·855-0·885], sensitivity of 83·1% [0·807-0·854], and specificity of 90·7% [0·889-0·924]) and the average non-medical student (accuracy of 77·2% [0·757-0·787], sensitivity of 76·6% [0·743-0·788], and specificity of 77·9% [0·759-0·797]). INTERPRETATION: Automated detection of OCSCC by deep-learning-powered algorithm is a rapid, non-invasive, low-cost, and convenient method, which yielded comparable performance to that of human specialists and has the potential to be used as a clinical tool for fast screening, earlier detection, and therapeutic efficacy assessment of the cancer.

Elucidating J-Aggregation Effect in Boosting Singlet-Oxygen Evolution Using Zirconium-Porphyrin Frameworks: A Comprehensive Structural, Catalytic, and Spectroscopic Study.

Metal-organic frameworks (MOFs) are powerful toolkits to directly correlate structure-function relationships due to their well-defined structures. In this work, 5,15-di(3,4,5-trihydroxyphenyl)porphyrin (DTPP) and 5,10,15,20-tetra(3,4,5-trihydroxyphenyl)porphyrin (TTPP) are reacted with zirconium ions to afford two MOFs (Zr-DTPP and Zr-TTPP) with acid and base tolerance in the pH range of 1.0-14.0. Powder X-ray diffraction investigation combined with Rietveld refinement reveals the J-aggregated porphyrin building blocks confined by benzene-1,2,3-trisolate-zirconium chains in the newly prepared Zr-DTPP. Electron spin-resonance, singlet-oxygen determination, and sulfides oxidation experiments demonstrate a much better singlet-oxygen evolution of J-aggregated Zr-DTPP than that of unaggregated Zr-TTPP reported previously, in good contrast to the weaker photocatalytic capability disclosed for DTPP than that for TTPP in solution, consummating the theory of photosensitizer J-aggregation in boosting heterogeneous photoinduced singlet-oxygen generation.

Functional Supramolecular Gels Based on the Hierarchical Assembly of Porphyrins and Phthalocyanines.

Supramolecular gels containing porphyrins and phthalocyanines motifs are attracting increased interests in a wide range of research areas. Based on the supramolecular gels systems, porphyrin or phthalocyanines can form assemblies with plentiful nanostructures, dynamic, and stimuli-responsive properties. And these π-conjugated molecular building blocks also afford supramolecular gels with many new features, depending on their photochemical and electrochemical characteristics. As one of the most characteristic models, the supramolecular chirality of these soft matters was investigated. Notably, the application of supramolecular gels containing porphyrins and phthalocyanines has been developed in the field of catalysis, molecular sensing, biological imaging, drug delivery and photodynamic therapy. And some photoelectric devices were also fabricated depending on the gelation of porphyrins or phthalocyanines. This paper presents an overview of the progress achieved in this issue along with some perspectives for further advances.

Gender- and Age-Specific Differences in the Association of Hyperuricemia and Hypertension: A Cross-Sectional Study.

OBJECTIVE: Both hyperuricemia and hypertension have important clinical implications, but their relationship in terms of gender and age is still a matter of debate. In this study, we aimed to explore gender- and age-specific differences in this association between hyperuricemia and hypertension in a Chinese population. METHODS: A total of 78596 ostensibly healthy subjects (47781 men and 30815 women) were recruited. The association between hyperuricemia and hypertension was analyzed by multivariate logistic regression, and the analyses were stratified by gender and age. RESULTS: Overall prevalence of hypertension and hyperuricemia was significantly higher in males than in females. Increasing trends of hypertension prevalence in both genders as well as hyperuricemia prevalence in females were found along with aging. However, males showed a reduced trend in hyperuricemia prevalence with aging. Higher hypertension and hyperuricemia prevalence was found in young and middle-aged men than in women, but not in elderly people older than 70 years. Significantly increased risk of hypertension from hyperuricemia was found only in men with an adjusted odds ratio of 1.131 (P < 0.01), especially in the middle-aged male participants. However, such significant results were not found in women. Similarly, hyperuricemia was also an independent risk factor of increased systolic blood pressure and diastolic blood pressure in males, but not in females. CONCLUSION: We observed significantly higher overall prevalence of hyperuricemia and hypertension in men than in women. Men with hyperuricemia (particularly in middle age) had a significantly increased susceptibility of hypertension, while this significant association was not observed in women.