1.Association of the clinical profile and outcomes of Gestational Diabetes Mellitus Patients admitted in a Tertiary Hospital in Cebu City from January 2021 to December 2022.
Joshua H. SERVANDE ; Ma. Vircel DUYONGCO-TIU
Philippine Journal of Internal Medicine 2026;64(1):7-20
OBJECTIVES
This study aimed at determining the association of the clinical profile of patients with GDM to maternal and neonatal outcomes
METHODSThis single-center, retrospective, descriptive, cross-sectional chart review was conducted in a tertiary hospital in Cebu City to 229 patients with GDM admitted from January 2021 to December 2022.
RESULTSThe study revealed several significant associations. Hypertension was strongly linked with primary cesarean section (OR: 4.32, P-value 0.004); and severe pre-eclampsia (OR: 16.97, P-value: 0.000). Gravidity showed significant correlations with Ballard’s score (P-value: 0.013), birthweight (P-value: 0.045) and 5-minute APGAR score (P-value: 0.001). Parity was associated with birthweight (P-value: 0.011) and 5-minute APGAR score (P-value: 0.001). Weight gain during pregnancy was linked to birthweight (P-value: 0.004) and occurrence of congenital anomalies (OR: 1.26, P-Value: 0.032). Additionally, prenatal smoking was associated with 5-minute APGAR score (P-value: 0.006). Moreover, having a Small for Gestational Age (SGA) fetal growth status is associated with insulin-requiring mothers, (OR: 4.79, P-Value: 0.049); and a family history of diabetes was significantly associated with insulin therapy (OR: 5.38, P-value: 0.021).
CONCLUSIONPatients' clinical profile affect maternal and neonatal outcomes among patients with GDM. Careful consideration of these factors during the perinatal period may help reduce maternal and fetal risks
Tertiary Care Centers ; Smoking ; Pregnancy ; Diabetes, Gestational ; Hypertension ; Apgar Score
2.Quality of care among patients with acute heart failure at the emergency room and adherence of physicians at the University of the Philippines – Philippine General Hospital to the division of cardiovascular medicine – heart failure pathway:A retrospective cohort study.
Mark John D. SABANDO ; Felix Eduardo R. PUNZALAN ; Frances Dominique V. HO ; Tam Adrian P. AYA-AY ; Kevin Paul Da. ENRIQUEZ ; Marie Kirk A. MARAMARA ; Ronald Allan B. RODEROS ; Lauren Kay M. EVANGELISTA
Acta Medica Philippina 2026;60(2):22-32
OBJECTIVES
Clinical pathways (CPs) ensure adherence to heart failure (HF) management guidelines. To optimize quality care in a low resource setting, an evidence-based care pathway for the management of acute HF was implemented at the emergency department (ED) of the Philippine General Hospital (PGH), the designated national tertiary hospital and referral center. This study aimed to describe the characteristics of adults with acute HF admitted at the ED and evaluate the quality of care they received, measured using physician adherence to the hospital’s acute heart failure CP.
METHODSThis was a retrospective, descriptive cohort study. We reviewed the inpatient charts of all adult patients with acute HF admitted to the ED of the PGH and referred to the Division of Cardiovascular Medicine between December 1, 2022 and May 31, 2023. Quality of care was assessed based on adherence to quality indicators adapted from routine and conditional order sets detailed in the pathway. Descriptive statistics was utilized to describe patient characteristics, quality of care, and outcomes.
RESULTSTwo hundred thirty-six (236) patients were included, with a mean age of 51.8 years. Majority were male (53.4%); hypertension (61.4%) and ischemic heart disease (53.8%) were the most common comorbidities, and infection the most common precipitant of decompensation (60.6%). There were optimal adherence rates to routine orders, which included referrals to Internal Medicine and Cardiology, baseline vital signs monitoring, fluid intake and output monitoring, chest radiograph, complete blood count, blood urea nitrogen, sodium, potassium, prothrombin time, partial thromboplastin time, arterial blood gas, urinalysis, and N-terminal pro b-type natriuretic peptide. Conditional orders, such as oxygen support, focused echocardiography, thyroid - stimulating hormone, and the use of vasopressors, diuretics, and venous thromboembolism prophylactic agents, were optimally performed when warranted. However, we noted suboptimal adherence to certain resource-intensive conditional orders, such as hourly monitoring of urine output (61.4%), hooking to cardiac monitor (53.8%), and performance of 12-lead ECG within 10 minutes (56.8%). Further, only 43.9% of patients were referred to the intensive care unit. Troponin I, calcium, magnesium, and albumin were ordered in excess.
CONCLUSIONOverall adherence rate of physicians to the hospital’s Acute Heart Failure Pathway was satisfactory. Work is needed to improve adherence to hourly urine output monitoring, consistent hooking to cardiac monitor, and timely performance of 12-lead ECG – an effort that begins with expanding in-hospital diagnostic equipment and human resource supply. We recommend continuous pathway implementation with periodic evaluation and stakeholder feedback to further improve quality of care.
Human ; Male ; Female ; Middle Aged: 45-64 Yrs Old ; Adult ; Albumins ; Blood ; Blood Urea Nitrogen ; Calcium ; Cardiology ; Chart ; Charts ; Cohort Studies ; Critical Care ; Critical Pathways ; Diagnostic Equipment ; Disease ; Diuretics ; Echocardiography ; Electrocardiography ; Emergencies ; Emergency Service, Hospital ; Equipment And Supplies ; Evaluation Studies As Topic ; Feedback ; Heart ; Heart Diseases ; Heart Failure ; Hormones ; Hospitals ; Hospitals, General ; Humans ; Hypertension ; Indicators And Reagents ; Infection ; Infections ; Inpatients ; Intensive Care Units ; Internal Medicine ; Lead ; Magnesium ; Male ; Medicine ; Myocardial Ischemia ; Natriuretic Peptide, Brain ; Natriuretic Peptides ; Nitrogen ; Overall ; Oxygen ; Partial Thromboplastin Time ; Patients ; Peptides ; Philippines ; Physicians ; Potassium ; Prothrombin ; Prothrombin Time ; Quality Of Health Care ; Referral And Consultation ; Sodium ; Statistics ; Tertiary Care Centers ; Thorax ; Thromboembolism ; Thromboplastin ; Thyroid Gland ; Time ; Troponin ; Troponin I ; Universities ; Urea ; Urinalysis ; Urine ; Venous Thromboembolism ; Vital Signs ; Work ; Workforce
3.Cross-sectional study on health-seeking behavior and barriers to perceived usability of medication tracker among middle-aged adults in a community in Marikina City.
Angeli T. VASQUEZ ; Angela Renee V. TENORIO ; Winlaure Minda M. TENORIO ; Denise Marie Dominique Q. UY ; Criszella R. VALENTINO ; John Benedict E. VENTURA ; Jorel L. SANTOS ; Tristan Jourdan C. DELA CRUZ
Acta Medica Philippina 2026;60(5):26-37
BACKGROUND AND OBJECTIVES
Technological advancements are reshaping healthcare, particularly through mobile health (mHealth) applications that aid chronic disease management. Medication tracking apps, such as Simpill, have shown potential in improving outcomes for conditions like hypertension. However, disparities in digital literacy and concerns related to technology acceptance and privacy may hinder effective use. Grounded in the principles of the Design Thinking approach, this study sought to evaluate the relationship between health-seeking behavior (HSB), perceived barriers (PB), and the perceived usability (PU) of Simpill among middle-aged hypertensive adults. The research aimed to capture not only measurable associations but also to inform future app development through a user-centered lens that prioritizes empathy and real-world usability.
METHODSA quantitative, descriptive-correlational research design was employed to assess respondents’ HSB, PB, and PU related to Simpill. The study was guided by core phases of the Design Thinking framework, particularly empathize and define, to ensure a deep understanding of user needs and usability constraints. Data were collected using a four-part, researcher-modified questionnaire administered to 138 purposively selected middle-aged adults (30–59 years old) residing in Barangay Industrial Valley, Zone 6, Marikina City, Philippines. All participants had a confirmed diagnosis of hypertension. Correlational analyses, including Kendall’s Tau B, were conducted to examine relationships among the variables. The integration of Design Thinking informed the development and interpretation of questionnaire items, aligning them with real-world challenges experienced by the target users.
RESULTSThe study investigated the relationship between HSB, PB, and the PU of Simpill among 138 middle-aged hypertensive individuals. Most respondents were female (55.8%), aged 50–59 (47.8%), and employed in non health-related sectors (95.7%). HSB levels were gene rally high (mean = 3.23), particularly in actively seeking health information, while lower engagement was noted in routine vital sign monitoring. PB were moderate (mean = 2.06), with unfamiliarity with the application cited as a common issue. PU was also rated as moderate (mean = 2.80), although ease of use received a low score (mean = 1.99). A weak positive correlation was found between HSB and PU (Kendall’s Tau B = 0.123, p = 0.049), while a moderate negative correlation existed between PB and PU (Tau B = -0.402, p < 0.001). These findings reflect insights derived from the Design Thinking "empathize" phase, suggesting that while proactive health behaviors may modestly support app engagement, unresolved user pain points—such as poor usability and lack of familiarity—remain significant obstacles to adoption. The results underscore the importance of moving to the "ideate" and "prototype" phases, where such user insights can directly shape the redesign and improvement of mHealth tools.
CONCLUSIONThe study identified a high level of health- seeking behavior, reflecting the respondents’ engagement with their health and openness to guidance, consistent with the user-empathy foundation of Design Thinking. Moderate perceived barriers highlight existing challenges in technology adaptation, particularly among those who prefer traditional methods. The moderate PU rating of Simpill, especially in terms of ease of use, suggests the app’s current design does not fully align with user capabilities or expectations. In line with Design Thinking principles, particularly user-centered innovation, the findings emphasize the need to involve users in iterative co-design processes to improve mHealth solutions. Addressing perceived barriers through enhanced digital literacy, usability testing, and interface refinement could substantially boost app acceptance and effectiveness in real-world settings.
Human ; Hypertension ; Mobile Applications ; Health Behavior ; User-centered Design
4.Renovascular hypertension in a young female with renal vein congestion and a left renal/gonadal vein aneurysm successfully treated with coiling.
Rossel Anjelo A. AMBAL ; Beatrice Louee S. ANTONIO ; Jaime Alfonso M. AHERRERA
Philippine Journal of Cardiology 2026;54(S1):41-44
INTRODUCTION
Secondary hypertension should be suspected among young individuals and patients with recent onset of hypertension or drug-resistant hypertension. Among the causes of secondary hypertension, renovascular hypertension is well-established and correctible if diagnosed appropriately. We report the case of a young female with an unusual cause of renovascular hypertension.
CLINICAL PRESENTATION:A 29-year-old female was admitted for elevated blood pressure and headache, unresponsive to multiple antihypertensives. The workup for secondary hypertension was mostly unremarkable. However, renal Doppler ultrasound showed elevated peak systolic velocity in the left renal artery. CT angiogram revealed an outpouching between the left gonadal and renal veins. No renal artery stenosis was found on renal angiography, but venography revealed an aneurysm between the left gonadal and renal veins. An aberrant vein draining into the inferior vena cava (IVC) and severe reflux into a dilated left gonadal vein were also noted.
MANAGEMENTCONCLUSIONThis case highlights a rare cause of renovascular hypertension due to renal vein congestion from severe left gonadal vein reflux and a renal/gonadal vein aneurysm. Additional mechanisms may include external compression of the renal artery or a suction effect caused by multiple venous outflows. Regardless of the exact pathophysiology, coiling of the aneurysm and gonadal vein successfully restored normal venous return and resolved hypertension.
Human ; Female ; Adult: 25-44 Yrs Old ; Veins ; Research Report ; Renal Veins ; Pharmaceutical Preparations ; Patients ; Hypertension, Renovascular ; Hypertension ; Female ; Aneurysm
5.Qingda Granule Attenuates Hypertension-Induced Cardiac Damage via Regulating Renin-Angiotensin System Pathway.
Lin-Zi LONG ; Ling TAN ; Feng-Qin XU ; Wen-Wen YANG ; Hong-Zheng LI ; Jian-Gang LIU ; Ke WANG ; Zhi-Ru ZHAO ; Yue-Qi WANG ; Chao-Ju WANG ; Yi-Chao WEN ; Ming-Yan HUANG ; Hua QU ; Chang-Geng FU ; Ke-Ji CHEN
Chinese journal of integrative medicine 2025;31(5):402-411
OBJECTIVE:
To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved.
METHODS:
Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively.
RESULTS:
The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01).
CONCLUSIONS
Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals
;
Drugs, Chinese Herbal/therapeutic use*
;
Hypertension/pathology*
;
Renin-Angiotensin System/drug effects*
;
Rats, Inbred SHR
;
Oxidative Stress/drug effects*
;
Male
;
Rats, Inbred WKY
;
Blood Pressure/drug effects*
;
Myocardium/pathology*
;
Rats
;
Inflammation/pathology*
6.Efficacy and Safety of Yangxue Qingnao Pills Combined with Amlodipine in Treatment of Hypertensive Patients with Blood Deficiency and Gan-Yang Hyperactivity: A Multicenter, Randomized Controlled Trial.
Fan WANG ; Hai-Qing GAO ; Zhe LYU ; Xiao-Ming WANG ; Hui HAN ; Yong-Xia WANG ; Feng LU ; Bo DONG ; Jun PU ; Feng LIU ; Xiu-Guang ZU ; Hong-Bin LIU ; Li YANG ; Shao-Ying ZHANG ; Yong-Mei YAN ; Xiao-Li WANG ; Jin-Han CHEN ; Min LIU ; Yun-Mei YANG ; Xiao-Ying LI
Chinese journal of integrative medicine 2025;31(3):195-205
OBJECTIVE:
To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension.
METHODS:
This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups.
RESULTS:
A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period.
CONCLUSIONS
Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans
;
Amlodipine/adverse effects*
;
Drugs, Chinese Herbal/adverse effects*
;
Male
;
Female
;
Hypertension/complications*
;
Middle Aged
;
Treatment Outcome
;
Drug Therapy, Combination
;
Adult
;
Blood Pressure/drug effects*
;
Double-Blind Method
;
Aged
;
Antihypertensive Agents/adverse effects*
7.Effectiveness of Xuanshen Yishen Decoction on Intensive Blood Pressure Control: Emulation of a Randomized Target Trial Using Real-World Data.
Xiao-Jie WANG ; Yuan-Long HU ; Jia-Ming HUAN ; Shi-Bing LIANG ; Lai-Yun XIN ; Feng JIANG ; Zhen HUA ; Zhen-Yuan WANG ; Ling-Hui KONG ; Qi-Biao WU ; Yun-Lun LI
Chinese journal of integrative medicine 2025;31(8):677-684
OBJECTIVE:
To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension.
METHODS:
Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate.
RESULTS:
The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse.
CONCLUSIONS
XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult
;
Aged
;
Female
;
Humans
;
Male
;
Middle Aged
;
Antihypertensive Agents/pharmacology*
;
Blood Pressure/drug effects*
;
Drugs, Chinese Herbal/pharmacology*
;
Hypertension/physiopathology*
;
Patient Readmission
;
Treatment Outcome
8.Mechanism of Sangqi Qingxuan Liquid in Alleviating Vascular Endothelial Injury in Hypertension Focuses on β-Catenin.
Wei-Quan REN ; Xin ZENG ; Jiang-Quan LIAO ; Li HUANG ; Lin LI
Chinese journal of integrative medicine 2025;31(8):726-734
OBJECTIVE:
To explore the main components and potential mechanisms of Sangqi Qingxuan Liquid in the treatment of arterial vascular endothelial cells (AVECs) injury in hypertension through network pharmacology.
METHODS:
Traditional Chinese Medicine Systems Pharmacology and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID) were used to screen the active components of Sangqi Qingxuan Liquid (SQQX), which met the oral utilization rate and drug similarity criteria. An active component-target network was constructed using Cytoscape 3.6 software. A protein-protein interaction (PPI) network of targets associated with SQQX treatment for hypertension was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The Metascape database was used to perform enrichment analysis of gene ontology biological functions and MSigDB pathway enrichment analysis of proteins in the PPI network. Further analysis of the main components of SQQX was performed using UPLC-MS. Based on the results of network pharmacology, the mechanism of SQQX to improve the injury of AVECs in hypertension was verified through lentiviral transfection by Wnt/ β -catenin signaling pathway. AVECs induced by angiotensin II (Ang II ) was used to establish a model of endothelial function injury in hypertension. Cell viability, intracellular nitric oxide content, malonaldehyde content, and superoxide dismutase activity were measured to determine the optimal induction conditions. The optimal intervention conditions for SQQX were determined based on cell viability, cellular DNA activity, and the gradient method. The cells were further divided into blank, model, overexpression lentivirus negative control, overexpression lentivirus, overexpression lentivirus + SQQX intervention (2.47 mg/mL, 12 h), inhibition lentivirus negative control, inhibition lentivirus, and inhibition lentivirus + SQQX intervention (2.47 mg/mL, 12 h) groups. Finally, quantitative real-time PCR and Western blotting were performed to analyze the molecular mechanisms of SQQX in the Wnt/ β -catenin signaling pathway.
RESULTS:
The main SQQX components were betaine, buddleoside, and chlorogenic acid, in descending order. Network pharmacology analysis screened 12 pathways associated with the hypertensive vascular endothelium. The results showed that 1 µ mol/L for 12 h was the optimal condition for Ang II to induce AVECs injury, and 2.47 mg/mL SQQX intervention for 12 h was the optimal condition for treating AVECs injury. In the experimental validation based on the interaction network of the Wnt/ β -catenin signaling pathway, SQQX significantly decreased the expressions of β -catenin, Smad2, peroxisome proliferator-activated receptors (PPARs), endothelial nitric oxide synthase (eNOS), and endothelin-1 (ET-1) caused by the β -catenin overexpression lentivirus (P<0.05 or P<0.01). The function of vascular endothelial cells can be improved by the β -catenin inhibition lentivirus, and no obvious changes were observed after further intervention with SQQX.
CONCLUSION
SQQX may protect against AVECs injury by regulating the Wnt/β -catenin signaling pathway.
Drugs, Chinese Herbal/therapeutic use*
;
beta Catenin/metabolism*
;
Hypertension/metabolism*
;
Endothelial Cells/metabolism*
;
Protein Interaction Maps/drug effects*
;
Humans
;
Wnt Signaling Pathway/drug effects*
;
Network Pharmacology
;
Endothelium, Vascular/injuries*
;
Cell Survival/drug effects*
;
Angiotensin II/pharmacology*
;
Nitric Oxide/metabolism*
9.Vascular Protection of Neferine on Attenuating Angiotensin II-Induced Blood Pressure Elevation by Integrated Network Pharmacology Analysis and RNA-Sequencing Approach.
A-Ling SHEN ; Xiu-Li ZHANG ; Zhi GUO ; Mei-Zhu WU ; Ying CHENG ; Da-Wei LIAN ; Chang-Geng FU ; Jun PENG ; Min YU ; Ke-Ji CHEN
Chinese journal of integrative medicine 2025;31(8):694-706
OBJECTIVE:
To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction.
METHODS:
Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca2+ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway.
RESULTS:
Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca2+-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca2+ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05).
CONCLUSIONS
Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals
;
Angiotensin II
;
Male
;
Benzylisoquinolines/therapeutic use*
;
Network Pharmacology
;
Blood Pressure/drug effects*
;
Sequence Analysis, RNA
;
Mice
;
Hypertension/chemically induced*
;
Mice, Inbred C57BL
;
Calcium/metabolism*
10.Mediating role of insulin resistance in the relationship between hypertension and NAFLD and construction of its risk prediction model.
Yaxuan HE ; Honghui HE ; Yu CAO ; Fang WANG
Journal of Central South University(Medical Sciences) 2025;50(7):1188-1201
OBJECTIVES:
Non-alcoholic fatty liver disease (NAFLD) and hypertension are common metabolic disorders, both closely associated with insulin resistance (IR), suggesting potential shared pathological mechanisms. This study aims to investigate the mediating role of IR in the relationship between hypertension and NAFLD, and to evaluate the applicability and modeling value of various IR surrogate indices in predicting NAFLD risk.
METHODS:
A total of 280 976 individuals who underwent health examinations at the Health Management Center of the Third Xiangya Hospital of Central South University between August 2017 and December 2021 were included. NAFLD was diagnosed based on abdominal ultrasound findings, and hypertension was defined according to the criteria of the Chinese Guidelines for the Management of Hypertension. Demographic information, anthropometric indices, and biochemical parameters were collected, and multiple IR surrogate indices were constructed, including the triglyceride-glucose index (TyG) and its derivatives, as well as the metabolic score for insulin resistance (METS-IR). Group comparisons were performed between hypertensive and non-hypertensive participants, as well as between NAFLD and non-NAFLD participants. Pearson correlation analysis was applied to assess the associations of metabolic parameters and IR indices with NAFLD. Furthermore, mediation models were constructed to explore the mediating role of IR in the "hypertension-NAFLD" relationship. Finally, parametric models and machine learning algorithms were compared to evaluate their predictive performance and value in assessing NAFLD risk in this population.
RESULTS:
The prevalence of NAFLD was significantly higher in hypertensive individuals than in non-hypertensive participants (63.61% vs 33.79%, P<0.001), accompanied by elevated IR levels and adverse metabolic features. Correlation analysis and variable importance rankings across multiple models consistently identified TyG-waist circumference (TyG-WC) and METS-IR as the IR indices most strongly associated with NAFLD. In mediation analysis, the TyG-WC pathway explained 32.03% of the total effect, and the METS-IR pathway explained 17.02%. Interaction analysis showed that hypertension status may attenuate the mediating effect of IR (all interaction estimates were negative). In prediction model comparisons, the simplified model incorporating sex, age, WC, TyG-WC, and METS-IR demonstrated good performance in the test set. Logistic regression and its regularized form (LASSO regression) achieved an accuracy of 0.83, receiver operating characteristic (ROC)-area under the curve (AUC) of 0.91, and a Brier score of 0.12, comparable to ensemble models (random forest and XGBoost), with consistently stable performance across different algorithms.
CONCLUSIONS
IR plays a significant mediating role in the association between hypertension and NAFLD, with TyG-WC identified as a key indicator showing strong mechanistic relevance and predictive value. Risk prediction models based on IR surrogate indices demonstrate advantages in simplicity and interpretability, providing empirical support for the early screening and individualized prevention of NAFLD in the general population.
Humans
;
Non-alcoholic Fatty Liver Disease/complications*
;
Insulin Resistance
;
Hypertension/epidemiology*
;
Male
;
Female
;
Middle Aged
;
Risk Factors
;
Adult
;
Machine Learning
;
Triglycerides/blood*


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