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: 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

PURPOSE: This study compared the effects of Static stretching and Mulligan's Two-leg rotation about the Hamstring flexibility, Hip range of motion, and pain.METHODS: The subjects were allocated randomly into two groups: Static stretching group (n=13) and Mulligan's two leg rotation group (n=14). The study was designed with stretching protocols for four minutes and thirty seconds per day five times a week for three weeks in total. Measurements, including the Sit and reach test, Active/Passive Straight leg raise, and Visual analogue scale, were conducted before and after the intervention. The data were analyzed using a paired t-test and independent t-test.RESULTS: The flexibility of the two leg rotation group was higher than the static stretching group after the intervention. The post-sit and reach test value of the two leg rotation group was significantly higher than the pre-sit and reach test value of the static stretching group. In addition, the variance of the sit and reach test of the two leg rotation group was significantly higher than that of the static stretching group.CONCLUSION: These results showed that two leg rotation techniques have a positive effect on the changes in the sit and reach test and active straight leg raise test. Two leg rotation techniques can be recommended as a self-stretching and easier way to stabilize the lumbopelvic rhythm, reduce the stiffness of the muscle and relieve pain. This is effective in preventing muscle damage, enabling muscle relaxation and reducing the risk of injury to the spine during daily lives and in sports activities.
Hip ; Humans ; Leg ; Muscle Relaxation ; Muscle Stretching Exercises ; Pliability ; Range of Motion, Articular ; Spine ; Sports ; Young Adult

Achalasia is a motility disorder of the esophagus characterized by absence of peristalsis and failure of relaxation of lower esophagus sphincter. The introduction of high resolution manometry (HRM) and per-oral endoscopic myotomy (POEM) has made a new chapter in diagnosis and treatment of achalasia. HRM allows classify according to the subtype of achalasia, and help predict prognosis and therapeutic response. POEM is a minimally invasive, effective option for treating achalasia. The management of achalasia required tailored application of various therapies such as botox injection, pneumatic balloon dilatation, POEM, or Heller's myotomy. In this review, we state the important aspects of diagnosis as well as management of achalasia.
Consensus ; Diagnosis ; Dilatation ; Esophageal Achalasia ; Esophagus ; Manometry ; Peristalsis ; Prognosis ; Relaxation

The Chicago classification (CC) defines an esophagogastric junction outflow obstruction (EGJOO) as the presence of several instances of intact or weak peristalsis, elevated median integrated relaxation pressure above 15 mmHg, and a discrepancy from the criteria of achalasia. The revised CC addresses the potential etiology of EGJOO, including the early forms of achalasia, mechanical obstruction, esophageal wall stiffness, or manifestation of hiatal hernia. A 58-year-old woman visited the Presbyterian Medical Center with swallowing difficulty. The patient underwent a high resolution manometry (HRM) examination and was diagnosed with EGJOO. Chest CT was performed to exclude a mechanical obstruction as a cause, and CT revealed a subepithelial tumor (SET) at the upper part of the esophagogastric junction. Therefore, laparoscopic surgery was performed and eccentric muscular hypertrophy of the distal esophagus was observed. Longitudinal myotomy and Dor fundoplication were also performed. The histology findings of the surgical specimens were consistent with achalasia. This paper reports a case of early achalasia that was finally diagnosed by the histology findings, but was initially diagnosed as EGJOO using HRM and misdiagnosed as SET in the image study.
Classification ; Deglutition ; Esophageal Achalasia ; Esophagogastric Junction ; Esophagus ; Female ; Fundoplication ; Hernia, Hiatal ; Humans ; Hypertrophy ; Laparoscopy ; Manometry ; Middle Aged ; Peristalsis ; Protestantism ; Relaxation ; Tomography, X-Ray Computed

Mindfulness is a process in which all thoughts, feelings, sensations, and all phenomena that happen to me are uncritically recognized as they are, so that they are eventually accepted and released without identifying or automatically responding to them. The clinical effects of mindfulness-based therapy have already been demonstrated in several studies. However, consistent results have not been reported for the mechanism of mindfulness-based treatment. Thus, this review aimed to describe a systematic review of the literature and research on the mechanisms of mindfulness-based interventions. Experienced meditators showed a physiological change in a ‘wakeful hypometabolic state’ during mindfulness meditation. In mindfulness meditation, it is known that certain areas other than brain activation during relaxation are additionally activated, particularly activation of fronto-limbic and fronto-parietal neural networks. The psychological mechanisms include meta-cognitive awareness, emotion regulation, reduction of automatic and self-referential thinking, concentration control, self-compassion, improvement of value clarification and self-regulation, exposure, extinction, and reconsolidation. Of the brain regions with changes in activity associated with mindfulness meditation, prefrontal cortex, the default mode network including cortical midline structures were associated with emotion regulation, concentration control, and reduction of automatic and self-referential thinking. In addition, brain regions associated with mindfulness meditation have been reported in the hippocampus, amygdala, and medical frontal cortices associated with memory reconsolidation and fear extinction. Thus, mindfulness-based interventions have a psychological and neurobiological effect with a special mechanism different from other psychological interventions, so that mindfulness based intervention can be an effective therapeutic intervention with a different mechanism from other psychological techniques.
Amygdala ; Brain ; Frontal Lobe ; Hippocampus ; Meditation ; Memory ; Mindfulness ; Prefrontal Cortex ; Psychological Techniques ; Relaxation ; Self-Control ; Sensation ; Thinking