OBJECTIVE: To study hesperetin-induced vasorelaxation after depolarizing contraction in human umbilical veins (HUVs) to elucidate the role of L-type Ca²⁺ channel (LTCC) and related signaling pathway. METHODS: Isometric tension recording was performed in HUV rings pre-contracted with K⁺. Hesperetin relaxing mechanism was investigated using a LTCC opener (BayK8644) and blockers of cyclic nucleotides and phosphodiesterases (PDEs). Whole-cell patch-clamping in A7r5 cells, a rat vascular smooth muscle cell line, was performed to study the effect of hesperetin on LTCC current. RESULTS: After depolarizing precontraction, hesperetin induced HUV relaxation concentration-dependently and endothelium-independently; 1 mmol/L hesperetin reduced denuded HUV ring tension by 68.7% ± 4.3% compared to matching vehicle, osmolality, and time controls (P<0.0001). Importantly, hesperetin competitively inhibited BayK8644-induced contraction, shifting the half maximal effective concentration of BayK8644 response from 1.08 nmol/L [95% confidence interval (CI) 0.49-2.40] in vehicle control to 11.30 nmol/L (95% CI 5.45-23.41) in hesperetin (P=0.0001). Moreover, hesperetin elicited further vasorelaxation in denuded HUV rings pretreated with inhibitors of soluble guanylyl cyclase, adenylyl cyclase, PDE3, PDE4, and PDE5 (P<0.01), while rings pretreated with PDE1 inhibitors could not be relaxed by hesperetin (P>0.05). However, simultaneously applying inhibitors of soluble guanylyl cyclase and adenylyl cyclase could not inhibit hesperetin's effect (P>0.05). In whole-cell patch-clamping, hesperetin rapidly decreased LTCC current in A7r5 cells to 66.7% ± 5.8% (P=0.0104). CONCLUSIONS Hesperetin diminishes depolarizing contraction of human vascular smooth muscle through inhibition of LTCC, and not cyclic nucleotides nor PDEs. Our evidence supports direct LTCC interaction and provides additional basis for the use of hesperetin and its precursor hesperidin as vasodilators and may lead to future vasodilator drug development as a treatment alternative for cardiovascular diseases.
Hesperidin/pharmacology* ; Humans ; Calcium Channels, L-Type/metabolism* ; Umbilical Veins/physiology* ; Muscle Contraction/drug effects* ; Animals ; Rats ; Calcium Channel Blockers/pharmacology* ; Vasodilation/drug effects* ; Muscle Relaxation/drug effects*

OBJECTIVE: To evaluate the therapeutic effect of Yu Melody relaxation training (YMRT) combined with Jianpi Jieyu Decoction (JJD) in treating patients with insomnia disorders (ID). METHODS: In this randomized controlled study, 94 ID patients were included from Xiyuan Hospital, China Academy of Chinese Medical Sciences from September 2022 to January 2024. They were randomly assigned to the YMRT group (47 cases, YMRT plus JJD) and the control group (47 cases, oral JJD) using a random number table. Both treatment administrations lasted for 4 weeks, with a 2-week follow-up. The primary outcome was change in Insomnia Severity Index (ISI) scores from baseline to 4 weeks of intervention. Secondary outcomes included ISI response at week 4, as well as ISI, Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder 7-item (GAD-7) scores at baseline and weeks 1, 2, 3, 4, and 6. Additionally, Pittsburgh Sleep Quality Index (PSQI) scores were evaluated at baseline and weeks 4 and 6. Adverse events (AEs) were recorded and compared between groups. RESULTS: Five patients in each group did not complete the protocol requirements. The overall dropout rate was 10.64%. The full analysis set included all 47 cases in each group. The ISI score decreased significantly at week 4 from baseline in the YMRT group compared with the control group, with a between-group difference of -3.2 points [95% confidence interval (CI): -5.08 to -1.34; P<0.05]. The ISI response at week 4 in the YMRT group was significantly higher than that in the control group (85.11% vs. 51.06%), with a between-group difference of 34.05% (95% CI: 13.77% to 50.97%; P<0.05). At week 6, the YMRT group demonstrated greater reductions from baseline than the control group, with between-group differences of -2.1 points (-95% CI: -3.49 to -0.64; P<0.05) for PHQ-9 scores, -3.5 points (95% CI: -5.21 to -1.85; P<0.05) for PSQI scores, and -1.9 points (95% CI: -3.47 to -0.28; P<0.05) for GAD-7 scores. Moreover, at weeks 4 and 6, the ISI and PSQI scores in the YMRT group were significantly lower than those in the control group (P<0.05); and at week 6, the PHQ-9 score in the YMRT group was significantly lower (P<0.05). There was no significant difference in the incidence rates of AEs between the two groups (8.51% vs. 4.26%, P>0.05). CONCLUSIONS YMRT combined with oral JJD could improve sleep quality and alleviate depressive and anxiety symptoms in patients with ID. This combined therapy was effective and safe, and its effect was superior to oral JJD alone. (Registration No. ChiCTR2200063884).
Humans ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Relaxation Therapy/methods* ; Middle Aged ; Adult ; Treatment Outcome ; Combined Modality Therapy

The aim in this literature review was (1) to explore the physiologically and psychologically therapeutic benefits of forest bathing on adults suffering from pre-hypertension or hypertension, and (2) to identify the type, duration, and frequency of an effective forest bathing intervention in the management of pre-hypertension and hypertension, so as to provide directions for future interventions or research. The electronic databases PubMed, Cochrane Library, CINAHL, PsyINFO, and the China Academic Journals (CAJ) offered through the Full-text Database (CNKI) were searched for relevant studies published from the inception of the databases to April 2019. Of the 364 articles that were identified, 14 met the criteria for inclusion in this review. The synthesis of the findings in the included studies revealed that forest bathing interventions were effective at reducing blood pressure, lowering pulse rate, increasing the power of heart rate variability (HRV), improving cardiac-pulmonary parameters, and metabolic function, inducing a positive mood, reducing anxiety levels, and improving the quality of life of pre-hypertensive or hypertensive participants. Forest walking and forest therapy programs were the two most effective forest bathing interventions. Studies reported that practicing a single forest walking or forest therapy program can produce short-term physiological and psychological benefits. It is concluded that forest bathing, particularly forest walking and therapy, has physiologically and psychologically relaxing effects on middle-aged and elderly people with pre-hypertension and hypertension.
Adult ; Aged ; Aged, 80 and over ; Female ; Forests ; Humans ; Hypertension ; prevention & control ; Male ; Middle Aged ; Prehypertension ; prevention & control ; Relaxation Therapy ; statistics & numerical data ; Young Adult

Public health crises, such as the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since Dec. 2019, are widely acknowledged as severe traumatic events that impose threats not only because of physical concerns but also because of the psychological distress of infected patients. We designed an internet-based integrated intervention and evaluated its efficacy on depression and anxiety symptoms in patients infected by SARS-CoV-2.
Adult ; Anxiety ; therapy ; Betacoronavirus ; Cell Phone ; China ; Coronavirus Infections ; psychology ; Depression ; therapy ; Female ; Humans ; Internet ; Male ; Middle Aged ; Mindfulness ; Pandemics ; Pneumonia, Viral ; psychology ; Prospective Studies ; Psychological Distress ; Relaxation Therapy ; Self Care ; methods

BACKGROUND AND OBJECTIVES: Bone marrow-derived mesenchymal stem cells (BM-MSCs) are adult multipotent non-haematopoietic stem cells that have regeneration potential. The current study aimed to detect the ability of BM-MSCs to improve kidney and cardiac functions in adult rats with established chronic kidney disease. METHODS: Rats were divided into sham-operated control, untreated sub totally nephrectomised and treated sub totally nephrectomised groups. Body weight, kidney and cardiac tissue weights, plasma creatinine and urea levels and arterial blood pressure were measured. ECG was recorded, and an in vitro isolated heart study was performed. Results: Stem cell treatment decreased the elevated plasma creatinine and urea levels and decreased systolic, diastolic and mean arterial blood pressure values. These changes were accompanied by a decrease in glomerular hypertrophy with apparent normal renal parenchyma. Additionally, BM-MSCs shortened Q-To and Q-Tc intervals, all time to peak tension values, the half relaxation value at 30 min of reperfusion and the contraction time at 15 and 30 min of reperfusion. Moreover, stem cell treatment significantly increased the heart rate, QRS voltage, the peak tension at the 15- and 30-min reperfusion time points and the peak tension per left ventricle at the 30-min reperfusion time point compared to the pre-ischaemia baseline. BM-MSCs resolve inter muscular oedema and lead to the re-appearance of normal cardiomyocytes. This improvement occurs with the observations of BM-MSCs in renal and heart tissues. CONCLUSIONS: BM-MSCs can attenuate chronic kidney disease progression and the associated cardiac electrophysiological and inotropic dysfunction.
Adult ; Animals ; Arterial Pressure ; Body Weight ; Creatinine ; Electrocardiography ; Heart Rate ; Heart Ventricles ; Heart ; Humans ; Hypertrophy ; In Vitro Techniques ; Kidney ; Mesenchymal Stromal Cells ; Myocytes, Cardiac ; Nephrectomy ; Plasma ; Rats ; Regeneration ; Relaxation ; Renal Insufficiency, Chronic ; Reperfusion ; Stem Cells ; Urea ; Weights and Measures

This article reviewed the current knowledge on time-course manifestation of diabetic urethral dysfunction (DUD), and explored an early intervention target to prevent the contribution of DUD to the progression of diabetes-induced impairment of the lower urinary tract (LUT). In the literature search through PubMed, key words used included “diabetes mellitus,” “diabetic urethral dysfunction,” and “diabetic urethropathy.” Polyuria and hyperglycemia induced by diabetes mellitus (DM) can cause the time-dependent changes in functional and morphological manifestations of DUD. In the early stage, it promotes urethral dysfunction characterized by increased urethral pressure during micturition. However, the detrusor muscle of the bladder tries to compensate for inducing complete voiding by increasing the duration and amplitude of bladder contractions. As the disease progresses, it can induce an impairment of coordinated micturition due to dyssynergic activity of external urethra sphincter, leading to detrusor-sphincter dyssynergia. The impairment of relaxation mechanisms of urethral smooth muscles (USMs) may additionally be attributable to decreased responsiveness to nitric oxide, as well as increased USM responsiveness to α1-adrenergic receptor stimulation. In the late stage, diabetic neuropathy may play an important role in inducing LUT dysfunction, showing that the decompensation of the bladder and urethra, which can cause the decrease of voiding efficiency and the reduced thickness of the urothelium and the atrophy of striated muscle bundles, possibly leading to the vicious cycle of the LUT dysfunction. Further studies to increase our understandings of the functional and molecular mechanisms of DUD are warranted to explore potential targets for therapeutic intervention of DM-induced LUT dysfunction.
Ataxia ; Atrophy ; Diabetes Mellitus ; Diabetic Neuropathies ; Early Intervention (Education) ; Hyperglycemia ; Lower Urinary Tract Symptoms ; Muscle, Smooth ; Muscle, Striated ; Nitric Oxide ; Polyuria ; Relaxation ; Urethra ; Urinary Bladder ; Urinary Tract ; Urination ; Urothelium

Hyperglycemia-induced hemichorea (HGHC) is a rare but characteristic hyperkinetic movement disorder involving limbs on one side of the body. In a 75-year-old woman with a left-sided HGHC, conventional brain MR imaging showed very subtle T1-hyperintensity and unique gadolinium enhancement in the basal ganglia contralateral to movements. Multi-parametric MRI was acquired using pulse sequence with quantification of relaxation times and proton density by multi-echo acquisition. Myelin map was reconstructed based on new tissue classification modeling. In this case report of multi-parametric MRI, quantitative measurement of myelin change related to HGHC in brain structures and its possible explanations are presented. This is the first study to demonstrate myelin loss related to hyperglycemic insult in multi-parametric quantitative MR imaging.
Aged ; Basal Ganglia ; Brain ; Classification ; Extremities ; Female ; Gadolinium ; Humans ; Hyperglycemia ; Hyperkinesis ; Magnetic Resonance Imaging ; Movement Disorders ; Myelin Sheath ; Protons ; Relaxation

PURPOSE: To investigate the temperature-based differences of cortical bone ultrashort echo time MRI (UTE-MRI) biomarkers between body and room temperatures. Investigations of ex vivo UTE-MRI techniques were performed mostly at room temperature however, it is noted that the MRI properties of cortical bone may differ in vivo due to the higher temperature which exists as a condition in the live body. MATERIALS AND METHODS: Cortical bone specimens from fourteen donors (63 ± 21 years old, 6 females and 8 males) were scanned on a 3T clinical scanner at body and room temperatures to perform T1, T2*, inversion recovery UTE (IR-UTE) T2* measurements, and two-pool magnetization transfer (MT) modeling. RESULTS: Single-component T2*, IR-T2*, short and long component T2*s from bi-component analysis, and T1 showed significantly higher values while the noted macromolecular fraction (MMF) from MT modeling showed significantly lower values at body temperature, as compared with room temperature. However, it is noted that the short component fraction (Frac1) showed higher values at body temperature. CONCLUSION: This study highlights the need for careful consideration of the temperature effects on MRI measurements, before extending a conclusion from ex vivo studies on cortical bone specimens to clinical in vivo studies. It is noted that the increased relaxation times at higher temperature was most likely due to an increased molecular motion. The T1 increase for the studied human bone specimens was noted as being significantly higher than the previously reported values for bovine cortical bone. The prevailing discipline notes that the increased relaxation times of the bound water likely resulted in a lower signal loss during data acquisition, which led to the incidence of a higher Frac1 at body temperature.
Biomarkers ; Body Temperature ; Female ; Humans ; Incidence ; Magnetic Resonance Imaging ; Relaxation ; Tissue Donors ; Water

BACKGROUND: Nicardipine, a calcium channel blocker, is used to treat hypertension in pregnancy or preterm labor. The current study was conducted to investigate the relaxant effects of nicardipine on the isolated uterine smooth muscle of the pregnant rat.METHODS: We obtained uterine smooth muscle strips from pregnant female SD rats. After uterine contraction with oxytocin 10 mU/ml, we added nicardipine (10⁻¹² to 10⁻⁸ M) accumulatively every 20 min. We recorded active tension and frequency of contraction, and calculated EC₅ (effective concentration of 5% reduction), EC₂₅, EC₅₀, EC₇₅, and EC₉₅ of active tension and frequency of contraction using a probit model.RESULTS: Nicardipine (10⁻¹² to 10⁻⁸ M) decreased active tension and frequency of contraction in a concentration-dependent manner. The EC₅₀ and EC₉₅ of nicardipine in the inhibition of active tension of the uterine smooth muscle were 2.41 × 10⁻¹⁰ M and 3.06 × 10⁻⁷ M, respectively. The EC₅₀ and EC₉₅ of nicardipine in the inhibition of frequency of contraction of the uterine smooth muscle were 9.04 × 10⁻¹¹ and 4.18 × 10⁻⁷ M, respectively.CONCLUSIONS: Nicardipine relaxed and decreased the frequency of contraction of the uterine smooth muscle in a concentration-dependent pattern. It might be possible to adjust the clinical dosage of nicardipine in the obstetric field based on our results, but further clinical studies are needed to confirm them.
Animals ; Calcium Channels ; Female ; Humans ; Hypertension ; Muscle, Smooth ; Nicardipine ; Obstetric Labor, Premature ; Oxytocin ; Pregnancy ; Rats ; Relaxation ; Uterine Contraction ; Uterus

PURPOSE: This study evaluates the effect of behavioral relaxation training on distress and cancer screening intention of patients with upper gastrointestinal endoscopy.METHODS: The research was conducted in a non-equivalent control group posttest design. Data were collected from endoscopy subjects in B city from October to November of 2018. Fifteen minutes of behavioral relaxation training were provided to the experimental group (n=40) and traditional relaxation therapy methods were provided to the control group (n=40). Outcome measures were distress and cancer screening intention of patients with upper gastrointestinal endoscopy. Data were analyzed with a χ²-test, independent t-test, Fisher's exact test with SPSS/PC version 23.0.RESULTS: The objective discomfort (t=8.81, p<.001) of the experimental group was lower than that of the control group; there were no significant differences in the subjective discomfort (t=1.73, p=.088). The cancer screening intention (t=−5.85, p<.001) of the experimental group was significantly higher than that of the control group.CONCLUSION: Behavioral relaxation training was effective in heightening cancer screening intention. Therefore it can be usefully applied to increase cancer screening intention.
Early Detection of Cancer ; Education ; Endoscopy ; Endoscopy, Gastrointestinal ; Humans ; Intention ; Outcome Assessment (Health Care) ; Relaxation Therapy ; Relaxation