Flavonoids: Potential therapeutic agents for cardiovascular disease.

Flavonoids are found in the roots, stems, leaves, and fruits of many plant taxa. They are related to plant growth and development, pigment formation, and protection against environmental stress. Flavonoids function as antioxidants and exert anti-inflammatory effects in the cardiovascular system by modulating classical inflammatory response pathways, such as the TLR4-NF-ĸB, PI3K-AKT, and Nrf2/HO-1 signalling pathways. There is increasing evidence for the therapeutic effects of flavonoids on hypertension, atherosclerosis, and other diseases. The potential clinical value of flavonoids for diseases of the cardiovascular system has been widely explored. For example, studies have evaluated the roles of flavonoids in the regulation of blood pressure via endothelium-dependent and non-endothelium-dependent pathways and in the regulation of myocardial systolic and diastolic functions by influencing calcium homeostasis and smooth muscle-related protein expression. Flavonoids also have hypoglycaemic, hypolipidemic, anti-platelet, autophagy, and antibacterial effects. In this paper, the role and mechanism of flavonoids in cardiovascular diseases were reviewed in order to provide reference for the clinical application of flavonoids in the future.

Investigation of subclinical ocular inflammation in the aqueous humor of patients with myopia following bilateral sequential collamer lens implantation.

BACKGROUND: The aqueous humor, a transparent fluid secreted by the ciliary body, supports the lens of the eyeball. In this study, we analyzed the cytokine and chemokine profiles within the aqueous humor of the contralateral eye post-implantation of an implantable collamer lens (ICL) to evaluate potential subclinical inflammation in the second eye subsequent to ICL implantation in the first eye. METHODS: Aqueous humor samples were procured from both eyes of 40 patients (totaling 80 eyes) prior to bilateral ICL insertion. Subsequently, a comprehensive statistical analysis was conducted using the Luminex assay to quantify 30 different cytokines in these samples. RESULTS: Compared to the first eye, the aqueous humor of the second eye demonstrated decreased concentrations of IFN-γ (P = 0.038), IL-13 (P = 0.027), IL-17/IL-17 A (P = 0.012), and IL-4 (P = 0.025). No significant differences were observed in other cytokine levels between the two groups. Patients were then categorized based on the postoperative rise in intraocular pressure (IOP) in the first eye. The group with elevated IOP displayed elevated levels of EGF in the aqueous humor of the first eye (P = 0.013) and higher levels of PDGF-AB/BB in the aqueous humor of the second eye (P = 0.032) compared to the group with normal IOP. Within the elevated IOP group, the levels of EGF (P = 0.013) and IL-17/IL-17 A (P = 0.016) in the aqueous humor were lower in the second eye than in the first eye. In the normal IOP group, cytokine levels did not differ notably between eyes. CONCLUSION: Following sequential ICL implantation, it appears that a protective response may be activated to mitigate subclinical inflammation in the second eye induced by the initial implantation in the first eye. Additionally, the increase in IOP subsequent to surgery in the first eye may correlate with the presence of inflammatory mediators in the aqueous humor.

Ultrasound-based radiomics-clinical nomogram for noninvasive prediction of residual cancer burden grading in breast cancer.

PURPOSE: To assess the predictive value of an ultrasound-based radiomics-clinical nomogram for grading residual cancer burden (RCB) in breast cancer patients. METHODS: This retrospective study of breast cancer patients who underwent neoadjuvant therapy (NAC) and ultrasound scanning between November 2020 and July 2023. First, a radiomics model was established based on ultrasound images. Subsequently, multivariate LR (logistic regression) analysis incorporating both radiomic scores and clinical factors was performed to construct a nomogram. Finally, Receiver operating characteristics (ROC) curve analysis and decision curve analysis (DCA) were employed to evaluate and validate the diagnostic accuracy and effectiveness of the nomogram. RESULTS: A total of 1122 patients were included in this study. Among them, 427 patients exhibited a favorable response to NAC chemotherapy, while 695 patients demonstrated a poor response to NAC therapy. The radiomics model achieved an AUC value of 0.84 in the training cohort and 0.83 in the validation cohort. The ultrasound-based radiomics-clinical nomogram achieved an AUC value of 0.90 in the training cohort and 0.91 in the validation cohort. CONCLUSIONS: Ultrasound-based radiomics-clinical nomogram can accurately predict the effectiveness of NAC therapy by predicting RCB grading in breast cancer patients.

Application of contrast-enhanced ultrasound in diagnosis and grading of bladder urothelial carcinoma.

PURPOSE: To explore the application of contrast-enhanced ultrasound (CEUS) for the diagnosis and grading of bladder urothelial carcinoma (BUC). METHODS: The results of a two-dimensional ultrasound, color Doppler ultrasound and CEUS, were analyzed in 173 bladder lesion cases. The ultrasound and surgical pathology results were compared, and their diagnostic efficacy was analyzed. RESULTS: There were statistically significant differences between BUC and benign lesions in terms of color blood flow distribution intensity and CEUS enhancement intensity (both P < 0.05). The area under the time-intensity curve (AUC), rising slope, and peak intensity of BUC were significantly higher than those of benign lesions (all P < 0.05). The H/T (height H / basal width T)value of 0.63 was the critical value for distinguishing high- and low-grade BUC, had a diagnostic sensitivity of 80.0% and a specificity of 60.0%. CONCLUSION: The combination of CEUS and TIC can help improve the diagnostic accuracy of BUC. There is a statistically significant difference between high- and low-grade BUC in contrast enhancement intensity (P < 0.05); The decrease of H/T value indicates the possible increase of the BUC grade.

Computational Design of Peptide Assemblies.

With the ongoing development of peptide self-assembling materials, there is growing interest in exploring novel functional peptide sequences. From short peptides to long polypeptides, as the functionality increases, the sequence space is also expanding exponentially. Consequently, attempting to explore all functional sequences comprehensively through experience and experiments alone has become impractical. By utilizing computational methods, especially artificial intelligence enhanced molecular dynamics (MD) simulation and de novo peptide design, there has been a significant expansion in the exploration of sequence space. Through these methods, a variety of supramolecular functional materials, including fibers, two-dimensional arrays, nanocages, etc., have been designed by meticulously controlling the inter- and intramolecular interactions. In this review, we first provide a brief overview of the current main computational methods and then focus on the computational design methods for various self-assembled peptide materials. Additionally, we introduce some representative protein self-assemblies to offer guidance for the design of self-assembling peptides.

Ferroptosis in cardiovascular diseases: role and mechanism.

In multicellular organisms, regulatory cell death is a crucial aspect of growth and development. Ferroptosis, which was postulated roughly ten years ago, is a mode of cell death that differs from apoptosis, autophagy, and pyrodeath. This distinct pattern of cell death is triggered by an imbalance between oxidants and antioxidants and strongly associated with the metabolism of iron, lipids, amino acids, and glutathione. A growing body of research has implicated ferroptosis in the incidence and progression of many organ traumas and degenerative diseases. Recently, ferroptosis has gained attention as a crucial regulatory mechanism underlying the initiation and development of a variety of cardiovascular diseases, including myocardial ischemia/reperfusion injury, cardiomyopathy, arrhythmia, chemotherapy, and Corona Virus-2-induced cardiac injury. Pharmacological therapies that inhibit ferroptosis have great potential for the management of cardiovascular disorders. This review discusses the prevalence and regulatory mechanisms of ferroptosis, effect of ferroptosis on the immune system, significance of ferroptosis in cardiovascular diseases, and potential therapeutic value of regulating ferroptosis in a variety of heart diseases.

Peptidyl Virus-Like Nanovesicles as Reconfigurable "Trojan Horse" for Targeted siRNA Delivery and Synergistic Inhibition of Cancer Cells.

The self-assembly of peptidyl virus-like nanovesicles (pVLNs) composed of highly ordered peptide bilayer membranes that encapsulate the small interfering RNA (siRNA) is reported. The targeting and enzyme-responsive sequences on the bilayer's surface allow the pVLNs to enter cancer cells with high efficiency and control the release of genetic drugs in response to the subcellular environment. By transforming its structure in response to the highly expressed enzyme matrix metalloproteinase 7 (MMP-7) in cancer cells, it helps the siRNA escape from the lysosomes, resulting in a final silencing efficiency of 92%. Moreover, the pVLNs can serve as reconfigurable "Trojan horse" by transforming into membranes triggered by the MMP-7 and disrupting the cytoplasmic structure, thereby achieving synergistic anticancer effects and 96% cancer cell mortality with little damage to normal cells. The pVLNs benefit from their biocompatibility, targeting, and enzyme responsiveness, making them a promising platform for gene therapy and anticancer therapy.

Risk of hypovolemia associated with sodium-glucose cotransporter-2 inhibitors treatment: A meta-analysis of randomized controlled trials.

Aim of the review: To assess the risk of hypovolemia for sodium-glucose cotransporter-2 (SGLT2) inhibitors treatment. Method: A systematic literature retrieval was performed in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and Scopus from inception up to 4 October 2022, Data for study characteristics and outcomes of interest were extracted from each eligible study. Risk ratios (RRs) with a 95% confidence interval (CI) for hypovolemia were calculated using a random-effect model. Results: A total of 57 studies (n = 68,622) were included in our meta-analysis, with a result of 1,972 hypovolemia incidents (1,142 in the SGLT2 inhibitors group and 830 in the control group). The pooled RR was 1.12 (95% CI: 1.02-1.22). It is evident that receiving SGLT2 inhibitors increased the risk of hypovolemia. When stratified by category of SGLT2 inhibitors the result was consistent; when the subgroup was analyzed by age, the pooled RR was 1.07 (95% CI: 0.94-1.23) in patients aged ≥65 years and 1.14 (95% CI: 1.02-1.28) in those aged <65 years. When comparing the baseline estimated glomerular filtration rate (eGFR) of less than or equal to 60 mL/min/1.73 m2 with a baseline eGFR greater than 60 mL/min/1.73 m2, the pooled RR was 1.21, (95% CI: 1.00-1.46) and 1.08, (95%CI: 0.98-1.20), respectively. Conclusion: Our meta-analysis has demonstrated that SGLT2 inhibitors increased the risk of hypovolemia in patients with Type 2 Diabetes Mellitus (T2DM). It is necessary to pay attention to the risk of hypovolemia associated with SGLT2 inhibitors, especially in older individuals and those with moderate renal impairment. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020156254].

One-Step Synthesis of Peptide-Gold Nanoclusters with Tunable Fluorescence and Enhanced Gene Delivery Efficiency.

In this study, peptide-gold nanoclusters with tunable fluorescence were prepared by a simple "one-pot" method, which were used for gene localization and delivery in vivo to achieve efficient intracellular colocalization, uptake, and transfection. The efficiency of pDNA transfection was up to 70.6%, and there was no obvious cytotoxicity. This study proves that the simple-composition and bio-friendly peptide-gold nanoclusters are promising gene delivery carriers and can provide a powerful theoretical and experimental basis for the application of peptide-metal nanocomplexes in gene delivery and other biomedicine fields.

Risk factors and characteristics of ischemic stroke in patients with immune thrombocytopenia: A retrospective cohort study.

OBJECTIVES: Previous research has found that patients with immune thrombocytopenia (ITP) have an increased risk of thrombosis, such as venous thromboembolism (VT), ischemic stroke (IS)/transient ischemic attack (TIA), and cardiovascular disease (CVD), but the risk factors for stroke in patients with ITP have yet to be determined. This study aims to determine the risk factors and characteristics of ischemic stroke in patients with ITP. MATERIALS AND METHODS: This study included adults with incident primary ITP diagnosed in a tertiary medical center between 2010 and 2020. The t-test and Mann-Whitney U test were used to compare the variables between IS and non-IS groups, and the multivariate logistic regression model was employed to evaluate correlations. RESULTS: The study enrolled 1824 individuals, of whom 17 (0.93%) had IS, and 138 (1:8) were randomly chosen from 1807 non-IS patients. Age was found to be substantially associated with stroke in the multivariate analysis (OR 1.07, 95% CI: 1.026-1.116; p = 0.001). We found no correlation between platelet counts (PLT) (OR 1.013, 95% CI: 0.995-1.033; p = 0.164), mean platelet volume (MPV), platelet larger cell ratio (P-LCR), prothrombin time (PT) (OR 1.455, 95% CI 0.979-2.164; p = 0.064), activated partial thromboplastin time (APTT), D-dimer, fibrinogen or antinuclear antibody (ANA) and stroke. Of 17 ITP-IS patients, 7 (53.8%) were cryptogenic, greater than the general IS population. Three (23.1%) of them had an embolic pattern. CONCLUSION: For ITP patients, age was a significant predictor of stroke. ITP-IS patients had a more cryptogenic origin, with some showing an embolic pattern.

Detection of DNA methylation of HYAL2 gene for differentiating malignant from benign thyroid tumors / 南方医科大学学报

OBJECTIVE@#To assess the value of DNA methylation level of HYAL2 gene as a molecular marker for differential diagnosis of malignant and benign thyroid tumors.@*METHODS@#DNA methylation of HYAL2 gene in tissue specimens of 190 patients with papillary thyroid cancer (PTC) and 190 age- and gender-matched patients with benign thyroid tumors was examined by mass spectrometry, and the protein expression of HYAL2 was detected immunohistochemically for another 55 pairs of patients. Logistic regression analysis was performed to calculate the odds ratio (OR) and evaluate the correlation of per 10% reduction in DNA methylation with PTC. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) was calculated to assess the predictive value of alterations in HYAL2 methylation.@*RESULTS@#Hypomethylation of HYAL2_CpG_3 was significantly correlated with early-stage PTC (OR=1.51, P=0.001), even in stage I cancer (OR=1.42, P=0.007). Age-stratified analysis revealed a significantly stronger correlation between increased HYAL2_CpG_ 3 methylation and early-stage PTC in patients below 50 years than in those older than 50 years (OR: 1.89 vs 1.37, P < 0.05); ROC analysis also showed a larger AUC of 0.787 in younger patients. The results of immunohistochemistry showed that patients with PTC had significantly higher protein expressions of HYAL2 than patients with benign tumors.@*CONCLUSION@#The alterations of DNA methylation level of HYAL2 gene is significantly correlated with early-stage PTC, suggesting the value of DNA methylation level as a potential biomarker for differentiation of malignant from benign thyroid tumors.

The value of real-time contrast-enhanced ultrasound combined with CT enhancement in the differentiation of subtypes of renal cell carcinoma.

AIM: This study aimed to evaluate the value of real-time contrast-enhanced ultrasound (CEUS) combined with contrast-enhanced computed tomography (CECT) in the differential diagnosis of clear cell renal cell carcinoma (CCRCC), papillary renal cell carcinoma (PRCC), and chromophobe renal cell carcinoma (CRCC). MATERIALS AND METHODS: In the present study, 82 patients with CCRCC, 24 patients with PRCC, and 19 patients with CRCC were confirmed by pathology of the resected tumor. All patients were evaluated by CEUS and CECT before the operation. In addition, the contrast enhancement mode of CEUS and CECT and the contrast parameters of the region of interest (ROI) time-intensity curve between the lesions and the surrounding normal renal parenchyma by CEUS were compared and analyzed. RESULTS: Compared with the pathological results, the diagnostic accuracy of ultrasound in the 3 groups was 87.8% (72/82), 83.3% (20/24) and 73.7% (14/19). There was no significant difference between CEUS and CECT in the diagnostic accuracy of all groups (P>0.05). Meanwhile, compared with the surrounding renal parenchyma by CEUS, 82.5% (66/80) of CCRCC lesions showed "fast-forward and fast/slow-retrograde," while 83.3% (20/24) of PRCC, and 84.2% (16/19) showed "slow-forward and fast/slow-retrograde." Significant differences in the enhancement modes of CEUS were found among the CCRCC, PRCC, and CRCC lesions (P < 0.05). And the enhancement modes could be quantitatively analyzed by the ROI time-intensity curve of the lesion. Moreover, lesions enhanced by CECT and 74.4% (61/82) of CCRCC lesions showed "fast-forward and fast/slow-retrograde," while 66.7% (16/24) of PRCC and 84.2% (16/19) of CRCC showed "slow-forward and fast/slow-retrograde." The contrast modes and enhancement uniformity of CEUS and CECT showed no significant differences among the CCRCC, PRCC, and CRCC lesions (P > 0.05). CONCLUSION: CEUS and quantitative analysis of ROI time-intensity curve can be used for differential diagnosis of the 3 RCC subtypes. The combination of CEUS and CECT can help us differentiate RCC subtypes and is of great significance for clinical treatment strategies and prognostication.

State of the art in parallel ankle rehabilitation robot: a systematic review.

BACKGROUND: The ankle joint complex (AJC) is of fundamental importance for balance, support, and propulsion. However, it is particularly susceptible to musculoskeletal and neurological injuries, especially neurological injuries such as drop foot following stroke. An important factor in ankle dysfunction is damage to the central nervous system (CNS). Correspondingly, the fundamental goal of rehabilitation training is to stimulate the reorganization and compensation of the CNS, and to promote the recovery of the motor system's motor perception function. Therefore, an increasing number of ankle rehabilitation robots have been developed to provide long-term accurate and uniform rehabilitation training of the AJC, among which the parallel ankle rehabilitation robot (PARR) is the most studied. The aim of this study is to provide a systematic review of the state of the art in PARR technology, with consideration of the mechanism configurations, actuator types with different trajectory tracking control techniques, and rehabilitation training methods, thus facilitating the development of new and improved PARRs as a next step towards obtaining clinical proof of their rehabilitation benefits. METHODS: A literature search was conducted on PubMed, Scopus, IEEE Xplore, and Web of Science for articles related to the design and improvement of PARRs for ankle rehabilitation from each site's respective inception from January 1999 to September 2020 using the keywords " parallel", " ankle", and " robot". Appropriate syntax using Boolean operators and wildcard symbols was utilized for each database to include a wider range of articles that may have used alternate spellings or synonyms, and the references listed in relevant publications were further screened according to the inclusion criteria and exclusion criteria. RESULTS AND DISCUSSION: Ultimately, 65 articles representing 16 unique PARRs were selected for review, all of which have developed the prototypes with experiments designed to verify their usability and feasibility. From the comparison among these PARRs, we found that there are three main considerations for the mechanical design and mechanism optimization of PARRs, the choice of two actuator types including pneumatic and electrically driven control, the covering of the AJC's motion space, and the optimization of the kinematic design, actuation design and structural design. The trajectory tracking accuracy and interactive control performance also need to be guaranteed to improve the effect of rehabilitation training and stimulate a patient's active participation. In addition, the parameters of the reviewed 16 PARRs are summarized in detail with their differences compared by using figures and tables in the order they appeared, showing their differences in the two main actuator types, four exercise modes, fifteen control strategies, etc., which revealed the future research trends related to the improvement of the PARRs. CONCLUSION: The selected studies showed the rapid development of PARRs in terms of their mechanical designs, control strategies, and rehabilitation training methods over the last two decades. However, the existing PARRs all have their own pros and cons, and few of the developed devices have been subjected to clinical trials. Designing a PARR with three degrees of freedom (DOFs) and whereby the mechanism's rotation center coincides with the AJC rotation center is of vital importance in the mechanism design and optimization of PARRs. In addition, the design of actuators combining the advantages of the pneumatic-driven and electrically driven ones, as well as some new other actuators, will be a research hotspot for the development of PARRs. For the control strategy, compliance control with variable parameters should be further studied, with sEMG signal included to improve the real-time performance. Multimode rehabilitation training methods with multimodal motion intention recognition, real-time online detection and evaluation system should also be further developed to meet the needs of different ankle disability and rehabilitation stages. In addition, the clinical trials are in urgent need to help the PARRs be implementable as an intervention in clinical practice.

Enhancing Therapeutic Efficacy of Donepezil by Combined Therapy: A Comprehensive Review.

Combination therapy involving different therapeutic strategies mostly provides more rapid and effective results as compared to monotherapy in diverse areas of clinical practice. The most worldwide famous acetylcholinesterase inhibitor (AChEIs) donepezil for its dominant role in Alzheimer's disease (AD) has also attracted the attention of many pharmaceuticals due to its promising pharmacological potencies such as neuroprotective, muscle relaxant, and sleep inducer. Recently, a combination of donepezil with other agents has displayed better desirable results in managing several disorders, including the most common Alzheimer's disease (AD). This study involves all the data regarding the therapeutic effect of donepezil in its combination with other agents and explains its therapeutic targets and mode of action. Furthermore, this review also puts light on the current status of donepezil with other agents in clinical trials. The combination therapy of donepezil with symptomatic relief drugs and disease-modifying agents opens a new road for treating multiple pathological disorders. To the best of our knowledge, this is the first report encircling all the pharmacologic effects of donepezil in its combination therapy with other agents and their current status in clinical trials.

Internet-based patient- primary care physician-cardiologist integrated management model of hypertension in China: study protocol for a multicentre randomised controlled trial.

INTRODUCTION: The control rate of hypertension is low in China, especially in rural, western and minority areas. This is related to poor medical skills among physicians in primary care institutions and low levels of trust among patients. However, primary healthcare institutions are the main battleground for the prevention and treatment of hypertension. It is worth exploring how to most effectively integrate patients, primary care physicians and cardiologists in tertiary hospitals, to build a long-term mechanism for the prevention and treatment of hypertension. In this study, we aim to evaluate the clinical effectiveness and conduct a health economic evaluation of an internet-based patient-primary care physician-cardiologist integrated management model of hypertension in areas of China with different socioeconomic levels. METHODS AND ANALYSIS: This is a 12-month, multicentre, randomised controlled trial involving patients with hypertension in urban communities and rural areas of Sichuan Province, China. Each primary healthcare institution will cooperate with their tertiary hospital through the Red Shine Chronic Disease Management System (RSCDMS). Patients will be randomly assigned 1:1 to two groups: (1) a traditional care group; (2) an intervention group in which primary care physicians and cardiologists can share patient data and manage patients together through the RSCDMS. Patients can upload their blood pressure (BP) values and communicate with physicians using the system. The primary outcome is the change in systolic BP over a 12-month period. Secondary outcomes are changes in diastolic BP, BP control rate, values of 24-hour ambulatory BP monitoring, difference in cost-effectiveness between the groups, patient satisfaction, medication adherence and home BP monitoring compliance. All data will be recorded and stored in the RSCDMS and analysed using IBM SPSS V.26.0. ETHICS AND DISSEMINATION: This study has been approved by the Biomedical Research Ethics Committee of the West China Hospital of Sichuan University in Sichuan, China (No. 2020-148). Written informed consent will be obtained from all participants. The results of this study will be disseminated to the public through academic conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2000030677.

Risk of orthostatic hypotension associated with sodium-glucose cotransporter-2 inhibitor treatment: A meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this study was to assess the association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and the risk of orthostatic hypotension (OH) in patients with type 2 diabetes mellitus (T2DM). METHOD: A systematic literature retrieval was performed using PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception up to 16 October 2019. Data for study characteristics and outcomes of interest were extracted from each eligible study. Pooled risk ratios (RRs) with 95% confidence intervals (CI) for OH were calculated using a random-effects model. RESULT: A total of 16 studies (n = 12,749) were included in our meta-analysis, with a result of 44 incident OH cases (29 in the SGLT2 inhibitor group, and 15 in the control group). The pooled RR was 1.17 (95% CI: 0.65-2.09). There was no evidence that receiving SGLT2 inhibitors increased the risk of OH, when stratified by age, duration of T2DM, or placebo-control or active-control and baseline blood pressure. CONCLUSION: This meta-analysis suggested that, in general, SGLPT2 inhibitors did not increase the risk of OH in patients with T2DM. The possibility of OH should be, therefore, considered on an individual basis, especially in patients with a history of OH, long duration of T2DM, or comorbidities.

The Prevalence and Risk Factors of High-Altitude Pulmonary Hypertension Among Native Tibetans in Sichuan Province, China.

Gou, Qiling, Rufeng Shi, Xin Zhang, Qingtao Meng, Xinran Li, Xi Rong, Zhabu Gawa, Nage Zhuoma, and Xiaoping Chen. The prevalence and risk factors of high-altitude pulmonary hypertension among native Tibetans in Sichuan Province, China. High Alt Med Biol. 21:327-335, 2020. Background: Studies evaluating the prevalence and risk factors of high-altitude pulmonary hypertension (HAPH) are lacking. Objective: To determine the prevalence of HAPH and its correlated factors among highlanders living 3200 m above sea level in Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China. Methods: This was a single-center, cross-sectional study involving 1129 subjects (mean age 46.6 ± 14 years, 39% men). In native Tibetans, HAPH was defined as a mean pulmonary artery pressure >30 mmHg as measured by transthoracic echocardiography. Results: HAPH had a crude prevalence of 6.2% and was more prevalent in men than in women (8.6% vs. 4.6%, p = 0.005). Elderly adults were more likely to develop HAPH than young adults (odds ratio [OR] = 5.308, 95% confidence interval [CI] = 2.562-10.993). Highlanders with HAPH had more severe metabolic abnormalities (including elevated blood pressure, blood glucose, blood lipids, BMI, etc., p < 0.05) and significantly increased hemoglobin and hematocrit levels (p < 0.01). In multivariate logistic regression analysis, independent risk factors for HAPH were metabolic syndrome (OR = 3.128, 95% CI = 1.110-8.818), age (>60 years vs. <40 years) (OR = 2.924, 95% CI = 1.282-6.669), and decreased SpO2 (OR = 1.072 per 1-unit decrease; 95% CI = 1.010-1.136). Conclusion: It could be concluded that HAPH was prevalent among 6.2% of native Tibetans in Sichuan Province, China. Increasing age, metabolic syndrome, and decreased SpO2 were independent predisposing factors for HAPH.

Mini review: The FDA-approved prescription drugs that induce ovulation in women with ovulatory problems.

Infertility is defined as not being able to become pregnant after 12 months or more of unprotected sexual intercourse. Female infertility as a serious health issue can result from ovulation disorders, menstrual cycle problems, structural problems, and environmental factors. Ovulation occurs once a month between the time of menarche and menopause. The release of a mature egg from the ovary is controlled with the hypothalamic-pituitary-ovarian axis. Several hormones such as gonadotropin-releasing hormone (GnRH), FSH (follicle-stimulating hormone), LH (luteinizing hormone), estrogen, and progesterone play fundamental roles in the ovulation process. Both FSH and LH are the main treatment for women with ovulation disorders. Depending on the reasons for infertility, several different types of treatment are available for infertile women. Fertility drugs as an important part of treatment work like the natural hormones to treat infertility. Several fertility drugs can regulate ovulation and the release of an egg from the ovary in women with polycystic ovary syndrome (PCOS) or undergoing in vitro fertilization (IVF) treatment. This mini-review is about the FDA-approved prescription drugs that induce ovulation in women with ovulatory problems.

Liraglutide Lowers Body Weight Set Point in DIO Rats and its Relationship with Hypothalamic Microglia Activation.

OBJECTIVE: This study aimed to investigate the effects of liraglutide on the body weight set point (BWSP) in diet-induced obese rats and to determine the relationship between BWSP and hypothalamic arcuate nucleus (ARC) microglial activation. METHODS: Diet-induced obesity (DIO) rats were divided into three groups: continuous high-fat diet (HFD) plus saline, HFD with liraglutide, and HFD with liraglutide pair feeding. Body weight, BWSP, inflammatory cytokines, suppressor of cytokine signaling 3, orexigenic/anorexigenic proteins, apoptosis, and microglia in the ARC were assessed. The effect of liraglutide on the Notch-1 signaling pathway and its relationships with  nuclear factor-κB and p38 mitogen-activated protein kinase were also investigated in a lipopolysaccharide (LPS)-induced microglia activation model. RESULTS: Liraglutide reduced BWSP; reversed adverse changes in hypothalamic inflammation, suppressor of cytokine signaling 3, and apoptosis; and diminished microgliosis in DIO rats. The BWSP showed a linear correlation with ARC microglial density. Liraglutide inhibited LPS-induced M1 microglial polarization and promoted microglial polarization to the M2 phenotype, diminishing inflammatory cytokine expression. Liraglutide inhibited Notch-1 signaling pathway activation and decreased nuclear factor-κB and p38 mitogen-activated protein kinase pathway activation in LPS-stimulated microglia. CONCLUSIONS: Liraglutide can reduce BWSP in DIO rats. There is a linear correlation between hypothalamic microgliosis and BWSP. Liraglutide reduces excessive microglial activation and inflammation, which may contribute to BWSP reduction.

Evaluation of PTEN and CD4+FOXP3+ T cell expressions as diagnostic and predictive factors in endometrial cancer: A case control study.

To evaluate the potential role of Pten and CD4FOXP3 T cells in prognosis from endometrial cancer.Tissue samples and clinical data were collected from 200 patients with endometrial cancer and 100 control patients with benign uterine diseases. The expressions of Pten and CD4FOXP3 T cells were quantified by immunohistochemistry and immunofluorescence. After surgery, all patients were followed up for an average of 56.3 months. Surgical effects were evaluated based on the patients' symptoms and signs. A two-sided P value < .05 was considered significant.Pten diminished and CD4FOXP3 T cells significantly accumulated with the progression of endometial cancer, in comparison to the controls. Moreover, Pten expression was negatively correlated with the count of CD4FOXP3 T cells. Pten and CD4FOXP3 T cells were correlated with clinical characteristics, including tumor stage, differentiation and associated with patients' disease-free survival.Limited data were available between the expressions of Pten and CD4FOXP3 T cells in patients with endometrial cancer. Our study findings suggested that the expressions of Pten and CD4FOXP3 T cells might become possible biomarkers for the diagnosis and prediction in endometrial cancer.