Predictive model for totally implanted venous access ports­related long­term complications in patients with lung cancer.

Totally implanted venous access ports (TIVAPs), which are typically used in oncological chemotherapy and parenteral nutritional support, are convenient and safe, and thus offer patients a higher quality of life. However, insertion or removal of the device requires a minor surgical operation. Long-term complications (>30 days post insertion), such as catheter migration, catheter-related thrombosis and infection, are major reasons for TIVAP removal and are associated with a number of factors such as body mass index and hemoglobin count. Since management of complications is typically time-consuming and costly, a predictive model of such events may be of great value. Therefore, in the present study, a predictive model for long-term complications following TIVAP implantation in patients with lung cancer was developed. After excluding patients with a large amount of missing data, 902 patients admitted to The First Affiliated Hospital with Nanjing Medical University (Nanjing, China) were ultimately included in the present study. Of the included patients, 28 had complications, indicating an incidence rate of 3.1%. Patients were randomly divided into training and test cohorts (7:3), and three machine learning-based anomaly detection algorithms, namely, the Isolation Forest, one-class Support Vector Machines (one-class SVM) and Local Outlier Factor, were used to construct a model. The performance of the model was initially evaluated by the Matthew's correlation coefficient (MCC), area under curve (AUC) and accuracy. The one-class SVM model demonstrated the highest performance in classifying the risk of complications associated with the use of the intracavitary electrocardiogram method for TIVAP implantation in patients with lung cancer (MCC, 0.078; AUC, 0.62; accuracy, 66.0%). In conclusion, the predictive model developed in the present study may be used to improve the early detection of TIVAP-related complications in patients with lung cancer, which could lead to the conservation of medical resources and the promotion of medical advances.

The diagnostic efficiency of artificial intelligence based 2 hours Holter monitoring in premature ventricular and supraventricular contractions detection.

BACKGROUND: Electrocardiography (ECG) and 24 hours Holter monitoring (24 h-Holter) provided valuable information for premature ventricular and supraventricular contractions (PVC and PSVC). Currently, artificial intelligence (AI) based 2 hours single-lead Holter (2 h-Holter) monitoring may provide an improved strategy for PSVC/PVC diagnosis. HYPOTHESIS: AI combined with single-lead Holter monitoring improves PSVC/PVC detection. METHODS: In total, 170 patients were enrolled between August 2022 and 2023. All patients wore both devices simultaneously; then, we compared diagnostic efficiency, including the sensitivity/specificity/positive predictive-value (PPV) and negative predictive-value (NPV) in detecting PSVC/PVC by 24 h-Holter and 2 h-Holter. RESULTS: The PPV and NPV in patients underwent 2 h-Holter were 76.00%/87.50% and 96.35%/98.55, respectively, and the sensitivity and specificity were 79.17%/91.30%, and 95.65%/97.84% in PSVC/PVC detection compared with 24 h-Holter. The areas under the ROC curves (AUCs) for PSVC and PVC were 0.885 and 0.741, respectively (p < .0001). CONCLUSIONS: The potential advantages of the 2 h-Holter were shortened wearing period, improved convenience, and excellent consistency of diagnosis.

Construction of a Nomogram Model to Identify Atherosclerotic Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Approximately 50.0% of patients with type 2 diabetes mellitus (T2DM) experience macrovascular diseases, and nearly 80.0% of them succumb to macrovascular complications. Atherosclerotic cardiovascular disease (ASCVD) ranks among the most prevalent macrovascular complications in T2DM. In this study, we aim to develop a nomogram model for the early detection of ASCVD in T2DM patients, enabling us to provide valuable recommendations for the clinical prevention and management of macrovascular complications in this patient population. METHODS: This retrospective analysis encompassed 2620 T2DM patients admitted between June 2015 and June 2021. The cohort comprised 1270 T2DM patients with coexisting ASCVD (referred to as the "ASCVD group") and 1350 individuals who did not experience ASCVD (the "non-ASCVD group"). We conducted a comparative assessment of their baseline characteristics and clinical data. A nomogram model for the identification of ASCVD in T2DM patients was constructed utilizing Logistic regression analysis and the R package. The model's performance was evaluated through receiver operating characteristic (ROC) curve analysis and calibration curves. RESULTS: We developed a nomogram model for the identification of ASCVD in T2DM patients, incorporating ten variables: sex, age, hypertension, smoking history, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio, alanine transaminase (ALT), adenosine deaminase (ADA), postprandial 2-hour C-peptide, monocyte count (MONO), and eosinophil count (EOS). ROC curves demonstrated that the area under the curve (AUC) of the nomogram model for identifying ASCVD in T2DM patients was 0.673 for the training dataset (with a cut-off value of 0.473, specificity of 0.629, and sensitivity of 0.637) and 0.655 for the validation dataset (with a cut-off value of 0.460, specificity of 0.605, and sensitivity of 0.675). The calibration curve indicated a substantial agreement between the predicted and observed cases of ASCVD in the training dataset and an acceptable level of agreement in the validation dataset. CONCLUSIONS: The nomogram model effectively identifies ASCVD in T2DM patients, which can be instrumental in pinpointing the high-risk population for ASCVD among T2DM patients and facilitating timely clinical management.

Cost-effectiveness analysis of digital therapeutics for home-based cardiac rehabilitation for patients with chronic heart failure: model development and data analysis.

BACKGROUND: In recent years, numerous guidelines and expert consensus have recommended the inclusion of digital technologies and products in cardiac rehabilitation. Digital therapeutics (DTx) is an evidence-based medicine that uses digital means for data collection and monitoring of indicators to control and optimize the treatment, management, and prevention of disease. OBJECTIVE: This study collected and reviewed real-world data and built a model using health economics assessment methods to analyze the potential cost-effectiveness of DTx applied to home-based cardiac rehabilitation for patients with chronic heart failure. From the perspective of medical and health decision-makers, the economic value of DTx is evaluated prospectively to provide the basis and reference for the application decision and promotion of DTx. METHODS: Markov models were constructed to simulate the outcomes of DTx for home-based cardiac rehabilitation (DT group) compared to conventional home-based cardiac rehabilitation (CH group) in patients with chronic heart failure. The model input parameters were clinical indicators and cost data. Outcome indicators were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). The robustness of the evaluation methods and results was tested using sensitivity analyses. Clinical indicators, cost data, and health utility values were obtained from real-world data, including clinical study data, published literature, and public website information. RESULTS: The Markov model simulated a time span of 10 years, with a cycle set at one month, for 120 cycles. The results showed that the per capita cost of the CH group was 38,442.11 CNY/year, with a QALY of 0.7196 per person per year. The per capita cost of the DT group was 42,300.26 CNY/year, with a QALY of 0.81687 per person per year. The ICER per person was 39,663.5 CNY/QALY each year, which was below the willingness-to-pay threshold of 85,698 CNY (China's GDP per capita in 2022). CONCLUSIONS: DTx for home-based cardiac rehabilitation is an extremely cost-effective rehabilitation option compared with conventional home-based cardiac rehabilitation. DTx for home-based cardiac rehabilitation is potentially valuable from the perspective of healthcare decision-makers.

Reconfigurable Photonic Crystal Reversibly Exhibiting Single and Double Structural Colors.

Unlike absorption-based colors of dyes and pigments, reflection-based colors of photonic crystals, so called "structural colors", are responsive to external stimuli, but can remain unfaded for over ten million years, and therefore regarded as a next-generation coloring mechanism. However, it is a challenge to rationally design the spectra of structural colors, where one structure gives only one reflection peak defined by Bragg's law, unlike those of absorption-based colors. Here, we report a reconfigurable photonic crystal that exhibits single-peak and double-peak structural colors. This photonic crystal is composed of a colloidal nanosheet in water, which spontaneously adopts a layered structure with single periodicity (407 nm). After a temperature-gradient treatment, the photonic crystal segregates into two regions with shrunken (385 nm) and expanded (448 nm) periodicities, and thus exhibits double reflection peaks that are blue- and red-shifted from the original one, respectively. Notably, the transition between the single-peak and double-peak states is reversible.

Inactivated COVID-19 vaccine booster dose shortened the viral shedding time of patients infected with the Omicron variant BA.2.

OBJECTIVES: We assessed the effect of inactivated COVID-19 vaccine boosting immunization on the viral shedding time for patients infected with the Omicron variant BA.2. METHODS: We performed a real-world study by analyzing the outbreak data of patients infected with the COVID-19 Omicron variant BA.2 from March to May 2022 in Shanghai, China. Patients were categorized into three groups, including not fully vaccinated (zero and one dose), fully vaccinated (two doses), and booster-vaccinated (three doses). RESULTS: A total of 4443 patients infected with COVID-19 were included in the analysis. The proportion of viral shedding within 14 days in the three groups was 94.7%, 95.5%, and 96.7%, respectively (P <0.001). After adjusting for sex, age, underlying conditions, and clinical symptoms, the booster vaccination had a 29% increased possibility (hazard ratio: 1.29, 95% confidence interval: 1.18-1.41) of no detectable viral shedding within 14 days, whereas the fully vaccinated group had an 11% increased possibility of no detectable viral shedding (hazard ratio: 1.11, 95% confidence interval: 1.01-1.23). The effect of booster vaccination was more significant in males, the elderly, and people with underlying conditions or symptomatic infections. CONCLUSION: Our study confirmed that the booster vaccination could significantly shorten the viral shedding time of patients infected with the Omicron variant BA.2.

Characteristics and Occurrence Scenarios of Staff Exposed to SARS-CoV-2 Omicron in Shanghai Lingang Fangcang Shelter Hospital, CHINA.

Objective: To analyze the characteristics and occurrence scenarios of occupational exposure of staff in the Shanghai Lingang Fangcang Shelter Hospital. Methods: We collected the data of 80 staff with occupational exposure (including doctors, nurses, cleaning, security guards, and maintenance staff) in the Shanghai Lingang Fangcang Shelter Hospital from April 5 to May 20, 2022. The basic information of occupational exposure, factors influencing different occupational exposure types, ways to discover occupational exposure, discovery places of occupational exposure, and specific occurrence scenarios were compiled and analyzed among these data. Results: Occupational exposure mainly occurred in nurses (37, 46.25%), and cleaning (21, 26.25%). After the occurrence of occupational exposure, 20 staff (25%) did not know the occurrence time. Moreover, occupational exposure types were listed from high to low proportion as follows: broken protective clothing (56, 70%), mask loosening or displacement (13, 16.25%), skin exposure (6, 7.5%), and sharp object injuries (5, 6.25%). Occupational exposure was discovered mainly through self-discovery (56, 70%), while other discovery ways were majorly colleague discovery (12, 15%) and infection control supervisor discovery (12, 15%). Furthermore, occupational exposure was discovered principally in the public area (53.75%) and the office area (25%) of the cabin, but the proportion of mask loosening or displacement (38.46%) and skin exposure (50%) was also high in the first unloading area. Broken protective clothing occurred in the following scenarios: scratching while working in the cabin (37, 66.07%) and not knowing its occurrence time (25%). The occurrence scenarios of mask loosening or displacement were mainly not knowing its occurrence time (6, 46.15%), self-discovery (3, 23.08%), and at the time of removal (3, 23.08%). Conclusion: Targeted training and prevention of occupational exposure should be performed to decrease infection risk and ensure staff safety in Fangcang shelter hospitals.

Use of handheld electrocardiograph (SnapECG) for the remote monitoring of arrhythmias.

Objective: To investigate the value of a SnapECG monitoring in diagnosing arrhythmias compared with the conventional management. Methods: In the first phase, the SnapECG and 12-lead electrocardiogram (ECG) were simultaneously adopted to detect arrhythmias in 439 hospitalized patients. The accuracies of the SnapECG in detecting different arrhythmias were assessed. In the second phase, 62 patients with palpitations were randomized to receive the SnapECG monitoring or conventional management for 3 months. The diagnosis rate, time of diagnosis, episodes before diagnosis, associated expenses, and scores of the modified European Heart Rhythm Association (EHRA), Self-rating Anxiety Scale (SAS), and the 36-item short-form health survey questionnaire (SF-36) were compared between groups. Results: In the first phase, the SnapECG monitoring showed a sensitivity of 83.55% and specificity of 96.79% in identifying tachyarrhythmias, and a sensitivity of 95.29% and specificity of 97.54% in identifying bradyarrhythmias. In the second phase, 1642 ECGs were recorded by the SnapECG, among which 290 abnormal ECGs were identified. Compared with the conventional management, the SnapECG monitoring increased the diagnosis rate of symptomatic arrhythmias (70.97% vs. 19.35%, P < 0.05), shortened the time of diagnosis (48.26 ± 36.78 days vs. 71.45 ± 30.01 days, P < 0.05) and consequently reduced the episodes of symptomatic arrhythmias prior to establishing diagnosis. The scores of modified EHRA, SAS, SF-36 significantly improved at 3-month compared with their baseline levels in the SnapECG group. Conclusions: Remote monitoring with the SnapECG can achieve early diagnosis of symptomatic arrhythmias. However, its sensitivity in identifying P-wave-related arrhythmias warrants further improvement.

Vitamin D receptor deficiency increases systolic blood pressure by upregulating the renin-angiotensin system and autophagy.

The vitamin D receptor (VDR) may regulate blood pressure via multiple pathways. The present study investigated the underlying mechanism by which VDR deficiency increases blood pressure. A total of 16 8-week-old male littermate mice were randomly divided into the VDR knockout and wild-type groups (VDR-/- and VDR+/+ , respectively). Blood pressure was measured using a four-channel PowerLab data acquisition and ADI software analysis system. After euthanasia, vascular smooth muscle cells (VSMCs) were isolated from the VDR-/- and VDR+/+ mice. Oxidative stress, renin-angiotensin system (RAS) activation and autophagy markers were measured in the isolated VSMCs using reverse transcription-quantitative PCR (RT-qPCR), western blotting and transmission electron microscopy (TEM) assays. Mean systolic pressure was significantly higher in the VDR-/- mice compared with the VDR+/+ mice. RT-qPCR and western blotting analyses indicated that RAS markers (angiotensin II and II type 1 receptor) were significantly upregulated, oxidative stress was increased (evidenced by reduced superoxide dismutase and peroxiredoxin-4) and autophagy was activated (upregulation of autophagy related protein 7, Beclin 1 and microtubule-associated proteins 1A/1B light chain 3A) in the VDR-/- VSMCs compared with the VDR+/+ VSMCs. TEM demonstrated that there were more autophagy bodies in the VDR-/- VSMCs compared with the VDR+/+ VSMCs. In conclusion, VDR deficiency was associated with high blood pressure. The mechanism underlying the increase in blood pressure caused by VDR deficiency may involve activation of the RAS, as well as increased oxidative stress and autophagy of VSMCs.

Apelin receptor upregulation in spontaneously hypertensive rat contributes to the enhanced vascular smooth muscle cell proliferation by activating autophagy.

BACKGROUND: Proliferation of vascular smooth muscle cells (VSMCs) plays a vital role in the progression of vascular remodeling and hypertension. Apelin-13 promotes VSMC proliferation of normal rats. This study was designed to investigate the roles of apelin receptor (APJ) and apelin-13 in VSMC proliferation of hypertension rats and underlying mechanisms. METHODS: Primary VSMCs were obtained from aorta of Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR). The expressions of apelin and APJ were detected by Western bolt and PCR, as well as immunohistochemistry. VSMC proliferation was evaluated with CCK-8 kit, PCNA protein expression and percentage of EdU-positive cells. Autophagy was determined by the ratio of LC3BII to LC3BI, ATG5 and p62 protein expressions, as well as LC3B immunofluorescence. RESULTS: APJ expression was increased while apelin expression was reduced in aorta and VSMCs of SHR compared with those of WKY. Exogenous apelin-13 promoted VSMC proliferation and autophagy of both WKY and SHR, which were prevented by APJ antagonist F13A. Blockade of APJ had no significant effects on VSMC proliferation and autophagy of WKY, but attenuated VSMC proliferation and autophagy of SHR. Administration of autophagy inhibitor 3-methyladenine (3-MA) not only attenuated VSMC proliferation of SHR, but prevented apelin-13-induced VSMC proliferation of both WKY and SHR. CONCLUSIONS: Apelin-13 stimulates VSMC proliferation via APJ-mediated enhancement in autophagy. APJ upregulation in SHR contributes to the enhanced VSMC proliferation.

NLRP3 inflammasome inhibitor glyburide expedites diabetic-induced impaired fracture healing.

Localized inflammation is accompanied by the diabetic-induced fracture. The present study aims to investigate the therapeutic effects of glyburide, an NLRP3 inflammasome inhibitor, in a diabetic-induced fracture model. An animal model of diabetic-induced fracture was established and the mice were administrated with metformin or glyburide for 3 weeks. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to evaluate the relative expressions of IFN-γ, TNF-α, and IL-6. Micro-computed tomography (µCT) scanning was applied to evaluate bone callus formation. Histopathology examinations of fractured femur sections were performed using Tartrate-resistant acid phosphatase (TRAP) staining and Alcian blue and orange G staining. Bone strength was evaluated using Torsional testing. Our results showed that treatment of glyburide significantly decreased the expressions of IFN-γ, TNF-α, and IL-6 in the fracture calluses in diabetic-induced fracture model, while bone callus volume and bone volume fraction were increased. Additionally, our results also demonstrated that treatment of glyburide rescued the increase of osteoclasts in the bone-cartilage interface. Apart from decreasing a percentage of cartilage area and increasing the percentage of bone and fibrotic tissue area, treatment of glyburide increased the maximum torque and yield torque of fractures. These results implied that glyburide might be used as a potential drug candidate for diabetic-induced fracture.

GHRL Gene Leu72Met Polymorphism and Type 2 Diabetes Mellitus: A Meta-Analysis Involving 8,194 Participants.

Background: Although many studies indicate a positive correlation between GHRL gene Leu72Met polymorphism and an increased susceptibility to type 2 diabetes mellitus (T2DM), inconsistencies between independent studies still remain. Objective: Considering the inconsistencies between them, we have performed the current meta-analysis study. The objective of this study is to better examine the correlation of the GHRL gene Leu72Met polymorphism and T2DM. Methods: The current meta-analysis, involving 8,194 participants from 11 independent studies, was performed. A fixed effect model was used to evaluate the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs). Results: A significant association was found between T2DM and GHRL gene Leu72Met polymorphism under recessive (OR: 1.33, 95% CI: 1.01-1.76, P = 0.04), and homozygous genetic models (OR: 1.34, 95% CI: 1.01-1.78, P = 0.04) in the whole population. The correlation was more distinct in our subgroup analysis of the Chinese population under recessive (OR: 1.52, 95% CI: 1.07-2.15, P = 0.02), dominant (OR: 1.70, 95% CI: 1.38-2.10, P < 0.00001), additive (OR: 1.16, 95% CI: 1.02-1.33, P = 0.02), and homozygous genetic models (OR: 1.54, 95% CI: 1.07-2.20, P = 0.02). Conclusions: In short, GHRL gene Leu72Met polymorphism was significantly correlated with increased T2DM risk, particularly in the Chinese population. Individuals carrying the Met72 allele of GHRL Leu72Met gene polymorphism, particularly those of Chinese ancestry, may be more susceptible to developing T2DM disease.

Transient receptor potential vanilloid 4 is involved in the upregulation of connexin expression following pilocarpine-induced status epilepticus in mice.

Epilepsy is characterized by spontaneous seizures. Changes in the expression of the connexins (Cxs) have been reported to be involved in epileptogenesis. It has previously been shown that the transient receptor potential vanilloid 4 (TRPV4) plays an important role in the modulation of neuronal excitability, and that application of a TRPV4 antagonist blocks hyperthermia-induced seizures. Accordingly, in the present study, we sought to explore whether TRPV4 is involved in the regulation of Cx expression following pilocarpine-induced status epilepticus (PISE) in mice. We observed that TRPV4 protein levels in hippocampi increased 3 h to 30 d following PISE, peaking 1-3 d after induction, and that pre-application of the TRPV4 antagonist HC-067047 increased the latency to develop SE induced by pilocarpine and reduced the success rate of PISE preparation. We demonstrated that Cx43 protein levels followed a time profile similar to that of TRPV4, and further showed that the increase in Cx43 protein levels on 3 d post-PISE was markedly attenuated by HC-067047. In contrast, the corresponding increase in Cx32 protein levels lagged substantially behind, and these levels were unaffected by HC-067047. Similarly, the TRPV4 agonist GSK1016790A increased the mRNA and protein levels of Cx43, but not those of Cx32. We thus conclude that the upregulation of Cx43 expression by TRPV4 may be involved in the pathophysiology of epilepsy.

The CYP17A1 gene polymorphisms are associated with hypercholesterolemia in Han Chinese.

BACKGROUND: The CYP17A1 gene has been identified to associate with hypertension in Chinese population. However, the association between CYP17A1 polymorphisms and hypertension-related factors is unclear. The present study aimed to investigate the relation between CYP17A1 single nucleotide polymorphisms (SNPs) and serum lipid profiles. METHODS: In total, 1350 participants were included in the study. Six SNPs in or near CYP17A1 gene were genotyped in a Han Chinese population in two stages. RESULTS: There was a statistically significant association of rs1004467 (adjusted odds ratio = 0.783, 95% confidence interval = 0.667-0.919, p < 0.05) and rs11191548 (adjusted odds ratio = 0.788, 95% confidence interval = 0.672-0.925, p < 0.05) with hypercholesterolemia after adjustment for potential factors. Additionally, the rs1004467 minor G-allele and the rs11191548 minor C-allele were significantly associated with the lower serum total cholesterol levels (p < 0.05 for all). CONCLUSIONS: The rs1004467 and rs11191548 in the CYP17A1 gene are associated with a decreased risk of hypercholesterolemia and lower serum TC levels in Han Chinese.

Temperature-controlled repeatable scrambling and induced-sorting of building blocks between cubic assemblies.

Separation of a homogeneous mixture of different components to reach an ordered out-of-equilibrium state in solution has attracted continuous attention. While this can be achieved using external chemical fuels or photo energy, an alternative energy source is heat. Here we realize a temperature-controlled cycle of transitions between ordered and disordered states based on a mixture of two kinds of building blocks that self-assemble into cubic structures (nanocubes). An almost statistical mixture of nanocubes (disordered state) is thermodynamically most stable at lower temperature (25 °C), while homoleptic assemblies composed of single components are preferentially produced at higher temperature (100 °C) followed by rapid cooling. The scrambling of the building blocks between the nanocubes takes place through the exchange of free building blocks dissociated from the nanocubes. Based on this mechanism, it is possible to accelerate, retard, and perfectly block the scrambling by the guest molecules encapsulated in the nanocubes.

Cost-Effectiveness of Bariatric Surgery versus Medication Therapy for Obese Patients with Type 2 Diabetes in China: A Markov Analysis.

AIMS/INTRODUCTION: The present study estimated the cost-effectiveness of bariatric surgery versus medication therapy for the management of recently diagnosed type 2 diabetes mellitus (T2DM) in obese patients from a Chinese health insurance payer perspective. MATERIALS AND METHODS: A Markov model was established to compare the 40-year time costs and quality-adjusted life-years (QALYs) between bariatric surgery and medication therapy. The health-care costs in the bariatric surgery group, proportion of patients in each group with remission of diabetes, and state transition probabilities were calculated based on observed resource utilization from the hospital information system (HIS). The corresponding costs in the medication therapy group were derived from the medical insurance database. QALYs were estimated from previous literature. Costs and outcomes were discounted 5% annually. RESULTS: In the base case analysis, bariatric surgery was more effective and less costly than medication therapy. Over a 40-year time horizon, the mean discounted costs were 86,366.55 RMB per surgical therapy patient and 113,235.94 CNY per medication therapy patient. The surgical and medication therapy patients lived 13.46 and 10.95 discounted QALYs, respectively. Bariatric surgery was associated with a mean health-care savings of 26,869.39 CNY and 2.51 additional QALYs per patient compared to medication therapy. Uncertainty around the parameter values was tested comprehensively in sensitivity analyses, and the results were robust. CONCLUSIONS: Bariatric surgery is a dominant intervention over a 40-year time horizon, which leads to significant cost savings to the health insurance payer and increases in health benefits for the management of recently diagnosed T2DM in obese patients in China.

Associations of genetic polymorphisms of the vitamin D pathway with blood pressure in a Han Chinese population.

Vitamin D deficiency can lead to high blood pressure. Polymorphisms in the vitamin D hydroxylase gene have been associated with serum vitamin D levels in some Western countries. The aim of this study was to investigate whether polymorphisms of hydroxylase genes in the vitamin D metabolic pathway contribute to hypertension by affecting serum vitamin D status in a Han Chinese population. We selected four single nucleotide polymorphisms (SNPs; rs1993116 and rs10741657 of CYP2R1; rs4809957 and rs6068816 of CYP24A1) for genotyping in 525 control subjects and 324 hypertensive patients, and detected vitamin D levels in blood in subsets of these groups. The results showed that rs1993116 and rs10741657 were associated with a reduced risk of hypertension. The odds ratios, 95% confidence intervals, and p values from the adjusted additive and dominant models were 0.788 (0.644-0.963, p = 0.02) and 0.719 (0.545-0.949, p = 0.02) for rs1993116 and 0.805 (0.66-0.983, p = 0.033) and 0.733 (0.556-0.966, p = 0.028) for rs10741657. A protective effect of CYP2R1 with regard to hypertension was also found in males and non-smokers. The TT genotypes of rs1993116 and rs10741657 were associated with significantly lower systolic blood pressure in treated hypertensive patients (both p = 0.002). No association with hypertension was found for the two SNPs of CYP24A1, and no difference in vitamin D level was found among the three genotypes of the four SNPs. Our results suggest that CYP2R1 polymorphisms are associated with a reduced risk of hypertension independent of the vitamin D level in the Han Chinese population.

Galectin-3 exacerbates ox-LDL-mediated endothelial injury by inducing inflammation via integrin ß1-RhoA-JNK signaling activation.

Oxidized low-density lipoprotein (Ox-LDL)-induced endothelial cell injury plays a crucial role in the pathogenesis of atherosclerosis (AS). Plasma galectin-3 (Gal-3) is elevated inside and drives diverse systemic inflammatory disorders, including cardiovascular diseases. However, the exact role of Gal-3 in ox-LDL-mediated endothelial injury remains unclear. This study explores the effects of Gal-3 on ox-LDL-induced endothelial dysfunction and the underlying molecular mechanisms. In this study, Gal-3, integrin ß1, and GTP-RhoA in the blood and plaques of AS patients were examined by ELISA and western blot respectively. Their levels were found to be obviously upregulated compared with non-AS control group. CCK8 assay and flow cytometry analysis showed that Gal-3 significantly decreased cell viability and promoted apoptosis in ox-LDL-treated human umbilical vascular endothelial cells (HUVECs). The upregulation of integrinß1, GTP-RhoA, p-JNK, p-p65, p-IKKα, and p-IKKß induced by ox-LDL was further enhanced by treatment with Gal-3. Pretreatment with Gal-3 increased expression of inflammatory factors (interleukin [IL]-6, IL-8, and IL-1ß), chemokines(CXCL-1 and CCL-2) and adhesion molecules (VCAM-1 and ICAM-1). Furthermore, the promotional effects of Gal-3 on NF-κB activation and inflammatory factors in ox-LDL-treated HUVECs were reversed by the treatments with integrinß1-siRNA or the JNK inhibitor. We also found that integrinß1-siRNA decreased the protein expression of GTP-RhoA and p-JNK, while RhoA inhibitor partially reduced the upregulated expression of p-JNK induced by Gal-3. In conclusion, our finding suggests that Gal-3 exacerbates ox-LDL-mediated endothelial injury by inducing inflammation via integrin ß1-RhoA-JNK signaling activation.

Induced-fit expansion and contraction of a self-assembled nanocube finely responding to neutral and anionic guests.

Induced-fit or conformational selection is of profound significance in biological regulation. Biological receptors alter their conformation to respond to the shape and electrostatic surfaces of guest molecules. Here we report a water-soluble artificial molecular host that can sensitively respond to the size, shape, and charged state of guest molecules. The molecular host, i.e. nanocube, is an assembled structure consisting of six gear-shaped amphiphiles (GSAs). This nanocube can expand or contract its size upon the encapsulation of neutral and anionic guest molecules with a volume ranging from 74 to 535 Å3 by induced-fit. The responding property of this nanocube, reminiscent of a feature of biological molecules, arises from the fact that the GSAs in the nanocubes are connected to each other only through the hydrophobic effect and very weak intermolecular interactions such as van der Waals and cation-π interactions.