Comparative Safety Assessment of High and Low Doses of Anlotinib in Combination with PD-1 Monoclonal Antibody for Advanced Non-small Cell Lung Cancer Patients.

Background: The advent of immunotherapy has revolutionized non-small cell lung cancer (NSCLC) treatment. Anlotinib (AN), a multitargeted tyrosine kinase inhibitor, holds promise in combination with PD-1 monoclonal antibody therapy. Understanding the impact of optimal dosage is pivotal. Objective: This study aims to assess the comparative efficacy of high-dose AN versus low-dose AN when combined with PD-1 monoclonal antibody for the treatment of NSCLC. Methods: A total of 70 patients with NSCLC undergoing PD-1 monoclonal antibody therapy at our hospital from June 2020 to January 2022 were selected. The low-dose group (n=33) received AN at 8 mg and 10 mg. In comparison, the high-dose group (n=37) received AN at 12 mg. Comparative analyses included assessment of clinical efficacy, adverse reactions, prognosis, survival, changes in T lymphocyte subsets, inflammatory factors pre and post-chemotherapy, and treatment satisfaction. Results: No significant difference was observed in clinical efficacy and prognosis between the two groups (P > .05). The low-dose group exhibited fewer adverse reactions and inflammatory responses, along with improved immune function post-treatment (P < .05). Treatment satisfaction was higher in the low-dose group compared to the high-dose group (P < .05). Conclusions: Findings suggest that combining low-dose AN with PD-1 monoclonal antibody therapy is a safer approach in the treatment of advanced NSCLC. These findings advocate for the adoption of a tailored, lower-dose AN regimen, presenting a clinically sound and patient-centered strategy in the ongoing pursuit of optimized treatment modalities for advanced NSCLC.

Safety and efficacy of melatonin supplementation as an add-on treatment for infantile epileptic spasms syndrome: A randomized, placebo-controlled, double-blind trial.

This was a prospective, randomized, double-blind, single-center placebo-controlled trial to assess the efficacy and safety of melatonin as an add-on treatment for infantile epileptic spasms syndrome (IESS). Participants aged 3 months to 2 years with a primary diagnosis of IESS were recruited and assigned to two groups in a 1:1 ratio. Both treatment groups received a combination of adrenocorticotrophic hormone (ACTH) and magnesium sulfate (MgSO4 ) for 2 weeks, and the treatment group also received melatonin (3 mg) between 20:00 and 21:00 daily, 0.5-1 h before bedtime. The study's primary endpoint was the average reduction rate in spasm frequency assessed by seizure diaries. Secondary endpoints included assessment of the response rate, EEG hypsarrhythmia (Kramer score), and psychomotor development (Denver Developmental Screening Test, DDST). Sleep quality was assessed by using the Brief Infant Sleep Questionnaire (BISQ), the Infant Sleep Assessment Scale (ISAS), and actigraphy. Safety parameters were also evaluated. Statistical analyses were conducted on intention-to-treat and per-protocol populations. The trial is registered at Clinicaltrials.gov (ChiCTR2000036208). Out of 119 screened patients, 70 were randomized and 66 completed treatments. In the intention-to-treat population, there were no significant differences in the average percentage reduction of spasm frequency (median [interquartile range, IQR: Q3-Q1], 100% [46.7%] vs. 66.7% [55.3%], p = .288), the 3-day response rate (51.4% vs. 37.1%, p = .229), the 28-day response rate (42.9% vs. 28.6%, p = .212), EEG Kramer scores (2 [3.5] vs. 2 [3], p = .853), or DDST comprehensive months (5 [2.5] vs. 6 [6], p = .239) between the melatonin (n = 35) and placebo (n = 35) groups. However, caregivers reported improved sleep quality after melatonin treatment, with 85.7% reporting regular sleep compared to 42.9% with placebo (42.9%, p < .001). The melatonin group had lower ISAS scores in 4-11-month-old patients compared to the placebo (mean ± SD, 29.3 ± 4.4 vs. 35.2 ± 5.9, p < .001). Moreover, the median (IQR) value of sleep-onset latency was shortened by 6.0 (24.5) min after melatonin treatment, while that in the placebo group was extended by 3.0 (22.0) min (p = .030). The serum melatonin (6:00 h) level (pg/mL) of the children in the melatonin group after treatment was significantly higher than in the placebo group (median [IQR], 84.8 [142] vs. 17.5 [37.6], p < .001). No adverse effects related to melatonin were observed in the study, and there were no significant differences in adverse effects between the melatonin and placebo groups. Although not statistically significant, the results of this randomized clinical trial proved that melatonin supplementation, as an add-on treatment, can improve spasm control rate in the treatment of IESS. For IESS children treated with ACTH, the addition of melatonin was found to improve sleep quality, shorten sleep onset latency, and increase blood melatonin levels. Moreover, it was observed to be a safe treatment option.

Mindfulness-based therapy improves brain functional network reconfiguration efficiency.

Mindfulness-based interventions are showing increasing promise as a treatment for psychological disorders, with improvements in cognition and emotion regulation after intervention. Understanding the changes in functional brain activity and neural plasticity that underlie these benefits from mindfulness interventions is thus of interest in current neuroimaging research. Previous studies have found functional brain changes during resting and task states to be associated with mindfulness both cross-sectionally and longitudinally, particularly in the executive control, default mode and salience networks. However, limited research has combined information from rest and task to study mindfulness-related functional changes in the brain, particularly in the context of intervention studies with active controls. Recent work has found that the reconfiguration efficiency of brain activity patterns between rest and task states is behaviorally relevant in healthy young adults. Thus, we applied this measure to investigate how mindfulness intervention changed functional reconfiguration between rest and a breath-counting task in elderly participants with self-reported sleep difficulties. Improving on previous longitudinal designs, we compared the intervention effects of a mindfulness-based therapy to an active control (sleep hygiene) intervention. We found that mindfulness intervention improved self-reported mindfulness measures and brain functional reconfiguration efficiency in the executive control, default mode and salience networks, though the brain and behavioral changes were not associated with each other. Our findings suggest that neuroplasticity may be induced through regular mindfulness practice, thus bringing the intrinsic functional configuration in participants' brains closer to a state required for mindful awareness.

Effects of a prenatal mindfulness program on longitudinal changes in stress, anxiety, depression, and mother-infant bonding of women with a tendency to perinatal mood and anxiety disorder: a randomized controlled trial.

BACKGROUND: Stress is a risk factor for poor physical and mental health, affecting new mothers' ability, especially those with perinatal mood and anxiety disorders, to maintain their everyday lives. Over the past 50 years, global incidences of depression and anxiety disorders have increased, reaching pandemic levels. These incidences represent major public health issues that are challenging to detect and treat. Mindfulness programs are viable for reducing stress, anxiety, and depression. The present study evaluates mindfulness intervention effects on stress, anxiety, depression, and mother-infant bonding. METHODS: We collected data on 102 women participating in a prenatal mindfulness program between July 2021 and March 2022; they were parallel and randomly assigned to experimental or control groups. The intervention group received an 8-week course in a prenatal mindfulness program, and the control group received usual standard prenatal care. The self-reported stress, pregnancy-related anxiety, and depression were assessed before and after the intervention and at 36 weeks of gestation. At 2 and 4 months postpartum, all participants provided self-reported their levels of stress, depression, and quality of mother-infant bonding. RESULTS: Compared to the control group, the experimental group that received the prenatal mindfulness intervention experienced reduced prenatal stress, anxiety, and depression and reduced postnatal stress and depression. Despite this, there was no significant difference between the groups in terms of the quality of mother-infant bonding. CONCLUSIONS: Mindfulness prenatal programs are convenient and effective methods of decreasing stress, anxiety, and depression during the perinatal period. Based on our findings, prenatal mindfulness may play a role in mitigating mood and anxiety disorders and should be considered in future approaches to preventing psychological distress. TRIAL REGISTRATION NUMBER: This trial has been prospectively registered at ClinicalTrials.gov (NCT04693130) and the first registration date was 12/24/2020.

Exploring the anti-metastatic effects of Astragalus mongholicus Bunge-Curcuma aromatica Salisb. on colorectal cancer: A network-based metabolomics and pharmacology approach.

BACKGROUND: Colorectal cancer (CRC) is a common malignancy that can significantly diminish patients' quality of life. Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (AC) is an ancient Chinese medicinal combination used for the treatment of CRC. However, the core ingredients and targets involved in regulating lipid and amino acid metabolism in CRC remain unknown. We aimed to explore the key components and pharmacological mechanisms of AC in the treatment of CRC through a comprehensive analysis of network metabolomics, network pharmacology, molecular docking, and biological methods. METHODS: Ultra-performance liquid chromatography/mass spectrometry (MS) was used for quality control. Gas chromatography/MS and liquid chromatography/MS were used to detect metabolites in the feces and serum of CRC mice. A network pharmacology approach and molecular docking were used to explore the potential genes involved in the CRC-target-component network. The effect of AC on tumor immunity was investigated using flow cytometry and polymerase chain reaction. RESULTS: AC, high-dose AC, and 5-fluorouracil treatment reduced liver metastasis and tumor mass. Compared with the CRC group, 2 amino acid metabolites and 14 lipid metabolites (LPC, PC, PE) were upregulated and 15 amino acid metabolites and 9 lipid metabolites (TG, PE, PG, 12-HETE) were downregulated. Subsequently, through network analysis, four components and six hub genes were identified for molecular docking. AC can bind to ALDH1B1, ALDH2, CAT, GOT2, NOS3, and ASS1 through beta-Elemene, canavanine, betaine, and chrysanthemaxanthin. AC promoted the responses of M1 macrophages and down-regulated the responses of M2 macrophages, Treg cells, and the gene expression of related factors. CONCLUSION: Our research showed that AC effectively inhibited the growth and metastasis of tumors and regulated metabolism and immunity in a CRC mouse model. Thus, AC may be an effective alternative treatment option for CRC.

[Different processed products of Polygonati Rhizoma treat Alzheimer's disease in rats: urine metabolomics based on UPLC-Q/TOF-MS].

The study investigated the effects of different processed products of Polygonati Rhizoma(black bean-processed Polygonati Rhizoma, BBPR; stewed Polygonati Rhizoma, SPR) on the urinary metabolites in a rat model of Alzheimer's disease(AD). Sixty SPF-grade male SD rats were randomized into a control group, a model group, a donepezil group, a BBPR group, and a SPR group, with twelve rats in each group. Other groups except the control group were administrated with D-galactose injection(100 mg·kg~(-1)) once a day for seven weeks. The control group was administrated with an equal volume of normal saline once a day for seven consecutive weeks. After three weeks of D-galactose injection, bilateral hippocampal Aß_(25-35) injections were performed for modeling. The rats were administrated with corresponding drugs(10 mL·kg~(-1)) by gavage since week 2, and the rats in the model and control group with an equal volume of double distilled water once a day for 35 continuous days. The memory behaviour and pathological changes in the hippocampal tissue were observed. The untargeted metabolites in the urine were detected by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS). Principal component analysis(PCA) and orthogonal partial least square-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites and potential biomarkers, for which the metabolic pathway enrichment analysis was conducted. The results indicated that BBPR and SPR increased the new object recognition index, shortened the escape latency, and increased the times of crossing the platform of AD rats in the Morris water maze test. The results of hematoxylin-eosin(HE) staining showed that the cells in the hippocampal tissue of the drug administration groups were closely arranged. Moreover, the drugs reduced the content of interleukin-6(IL-6, P<0.01) and tumor necrosis factor-α(TNF-α) in the hippocampal tissue, which were more obvious in the BBPR group(P<0.05). After screening, 15 potential biomarkers were identified, involving two metabolic pathways: dicoumarol pathway and piroxicam pathway. BBPR and SPR may alleviate AD by regulating the metabolism of dicoumarol and piroxicam.

Psychobiotic supplementation of HK-PS23 improves anxiety in highly stressed clinical nurses: a double-blind randomized placebo-controlled study.

Nurses often experience adverse health effects associated with increasing levels of work-related stress. Stress may induce systemic effects through the HPA axis, glucocorticoid responses, and inflammatory cascades. Psychobiotics may help alleviate stress through associations of the microbiota, anti-inflammation factors, and the gut-brain axis. We aimed to investigate whether interventions with a psychobiotic, heat-killed (HK)-PS23 cells, may help improve perceived stress, anxiety, and related biological markers among highly stressed clinical nurses. This double-blind, randomized, placebo-controlled study included seventy clinical nurses from a medical center in Northern Taiwan who scored 27 or higher on the 10-item version of the Perceived Stress Scale (PSS), and participants were randomized into either taking HK-PS23 or a placebo for 8 weeks. Baseline and endpoint results of the PSS, Job Stress Scale, State and Trait Anxiety Index (STAI), emotional questionnaires, gastrointestinal severity questionnaires, Trails Marking Tests, blood biological markers, and sleep data were analyzed. While both groups demonstrated improvements in most measures over time, only the blood cortisol measure demonstrated significant group differences after the 8-week trial. Further analyses of the subgroup with higher anxiety (nurses with STAI ≥ 103) revealed that anxiety states had improved significantly in the HK-PS23 group but not in the placebo group. In summary, this placebo-controlled trial found significant reduction in the level of blood cortisol after 8 weeks of HK-PS23 use. The distinctive anxiolytic effects of HK-PS23 may be beneficial in improving perceived anxiety and stress hormone levels in female nurses under pressure. Clinical trial registration: https://clinicaltrials.gov/, identifier: NCT04452253-sub-project 1.

[Tea Polyphenols Regulate Renin-angiotensin-aldosterone System and Transforming Growth Factor-ß1/Smads Signaling Pathway in Heart Failure Rats].

Objective To investigate the effects of tea polyphenols on the renin-angiotensin-aldosterone system and the transforming growth factor-ß1(TGF-ß1)/Smads signaling pathway in heart failure rats.Methods SD rats were randomly assigned into a sham group,a model group,a captopril group(PC group),and a tea polyphenol group(TP group).The left anterior descending coronary artery was ligated with silk thread to establish the rat model of heart failure after myocardial infarction in the model group,PC group,and TP group,while it was not ligated in the sham group.Echocardiography was used to detect cardiac function.HE staining and Masson staining were conducted for the observation of myocardial pathological changes and myocardial fibrosis,respectively.Immunohistochemistry was employed to detect the expression of collagen Ⅰ and collagen Ⅲ.ELISA kits were used to measure the levels of angiotensin Ⅱ(AngⅡ),aldosterone(ALD),plasma renin activity(PRA),interleukin-1ß(IL-1ß),IL-6,and tumor necrosis factor-α(TNF-α).Western blotting was employed to determine the protein levels of TGF-ß1,phosphorylated Smad2(p-Smad2),Smad2,p-Smad3,and Smad3.Results Compared with the sham group,the model group showed disordered myocardial cells with obvious inflammatory cell infiltration,increased degree of myocardial fibrosis(t=9.748,P=0.001),elevated levels of collagen Ⅰ(t=11.754,P=0.001) and collagen Ⅲ(t=10.573,P=0.001),decreased ejection fraction(EF)(t=13.174,P=0.002) and left ventricular short axis shortening rate(LVFS)(t=11.853,P=0.001),and up-regulated expression of AngⅡ(t=4.246,P=0.001),ALD(t=5.385,P=0.004),PRA(t=4.386,P=0.004),IL-1ß(t=4.393,P=0.001),IL-6(t=6.375,P=0.002),and TNF-α(t=4.753,P=0.002),and up-regulated protein levels of TGF-ß1(t=6.365,P=0.001),p-Smad2/Smad2(t=13.755,P=0.001),and p-Smad3/Smad3(t=11.657,P=0.002).Compared with the model group,PC and TP alleviated the myocardial pathological changes,decreased the left ventricular end-diastolic diameter(LVEDd)(t=6.367,P=0.003 and t=5.264,P=0.003),left ventricular end-systolic diameter(LVEDs)(t=5.253,P=0.002 and t=5.974,P=0.001),heart mass index(HMI)(t=5.012,P=0.007 and t=4.953,P=0.005),left ventricular mass index(LVMI)(t=5.531,P=0.003 and t=5.483,P=0.004),and the degree of myocardial fibrosis(t=6.734,P=0.001 and t=5.362,P=0.001).Furthermore,they lowered the levels of collagen Ⅰ (t=5.373,P=0.001 and t=4.364,P=0.001) and collagen Ⅲ(t=6.764,P=0.001 and t=4.579,P=0.001),increased EF(t=11.264,P=0.002 and t=10.356,P=0.001) and LVFS(t=8.246,P=0.002 and t=7.824,P=0.001),and down-regulated the expression of AngⅡ(t=3.126,P=0.001 and t=2.853,P=0.001),ALD(t=3.854,P=0.004 and t=3.164,P=0.004),PRA(t=3.126,P=0.004 and t=3.063,P=0.004),IL-1ß(t=2.964,P=0.001 and t=2.765,P=0.001),IL-6(t=4.865,P=0.002 and t=4.275,P=0.002),and TNF-α(t=3.146,P=0.002 and t=2.973,P=0.002).In addition,they down-regulated the protein levels of TGF-ß1(t=4.657,P=0.001 and t=4.176,P=0.001),p-Smad2/Smad2(t=9.687,P=0.001 and t=6.753,P=0.001) and p-Smad3/Smad3(t=6.477,P=0.002 and t=4.754,P=0.002).Conclusion Tea polyphenols protect rats from heart failure by inhibiting the activation of renin-angiotensin-aldosterone system and TGF-ß1/Smads pathway.

[YANG Jun's clinical experience of acupuncture for oculomotor paralysis].

Professor YANG Jun's clinical experience of acupuncture and moxibustion for oculomotor paralysis is summarized. Professor YANG Jun pays attention to disease differentiation and syndrome differentiation in the treatment of this disease. According to the characteristics of oculomotor paralysis, "early diagnosis and seeking treatment from the source" is advocated. According to the etiology and pathogenesis, professor YANG divides oculomotor paralysis into three types: the syndrome of wind-evil attacking collaterals, the syndrome of spleen-stomach weakness and the syndrome of qi-deficiency and blood-stasis. As such, the acupoints are selected according to syndrome differentiation, and several different acupuncture methods (pricking needling at eyelids, penetrating needling and lifting eyelids and contralateral- balance needling on the healthy side) are adopted to improve the symptoms of oculomotor paralysis. It is also suggested to use the combination of scalp acupuncture and electroacupuncture to achieve the best dose-effect state. Moreover, local stimulation around the eyes is important to achieve the effects of "qi reaching affected area".

Applying Mindfulness Techniques to the Management of Depressive Tendencies in Women in Taiwan in the Perinatal Period: A Qualitative Study.

PURPOSE: Perinatal distress, especially depression, commonly occurs during pregnancy and the first year postpartum, but this medical condition are often undiagnosed and untreated. The present study explored how women with depressive symptoms during the perinatal period who had participated in a mindfulness course applied the training and perceived its effects. METHODS: This descriptive qualitative study included 16 women with probable perinatal depression who had participated in an 8-week mindfulness-based childbirth and parenting program during their pregnancy and agreed to be interviewed. One-to-one in-depth interviews were conducted and recorded following the completion of the mindfulness course, approximately 1 month after childbirth. Verbatim transcripts were analyzed using content analysis. RESULTS: We proposed three themes and six subthemes relating to first-time mothers' experiences during and after the group mindfulness-based intervention: learning to be aware of the body and mind (confronting awareness of physical change, managing negative feelings differently), building positive family relationships (strengthening the mother-baby bond, developing a satisfactory marital partnership), and overcoming ongoing challenges (conquering childbirth pain with confidence, accepting unexpected situations). Three main themes were generated to demonstrate how women experience the effects of mindfulness training. CONCLUSIONS: Mindfulness-based interventions helped the participants develop insight into their mood and physical changes and accept their childbirth process. Therefore, mindfulness education programs can be incorporated into prenatal care to enhance the management of the depressive symptoms of perinatal women.

YANG Jun's clinical experience of acupuncture for oculomotor paralysis / 中国针灸

Professor YANG Jun's clinical experience of acupuncture and moxibustion for oculomotor paralysis is summarized. Professor YANG Jun pays attention to disease differentiation and syndrome differentiation in the treatment of this disease. According to the characteristics of oculomotor paralysis, "early diagnosis and seeking treatment from the source" is advocated. According to the etiology and pathogenesis, professor YANG divides oculomotor paralysis into three types: the syndrome of wind-evil attacking collaterals, the syndrome of spleen-stomach weakness and the syndrome of qi-deficiency and blood-stasis. As such, the acupoints are selected according to syndrome differentiation, and several different acupuncture methods (pricking needling at eyelids, penetrating needling and lifting eyelids and contralateral- balance needling on the healthy side) are adopted to improve the symptoms of oculomotor paralysis. It is also suggested to use the combination of scalp acupuncture and electroacupuncture to achieve the best dose-effect state. Moreover, local stimulation around the eyes is important to achieve the effects of "qi reaching affected area".

Selective suppression of M1 macrophages is involved in zinc inhibition of liver fibrosis in mice.

Zinc deficiency is common in the liver of patients with chronic liver disease. Zinc supplementation suppresses the progression of liver fibrosis induced by bile duct ligation (BDL) in mice. The present study was undertaken to specifically investigate a possible mechanism by which zinc plays this role in the liver. Kunming mice were subjected to BDL for 4 weeks to induce liver fibrosis, and concomitantly treated with zinc sulfite or saline as control by gavage once a day. The results showed that zinc supplementation significantly suppressed liver fibrosis and inflammation along with inhibition of hepatic stellate cells activation induced by BDL. These inhibitory effects were accompanied by the reduction of collagen deposition and a significant reduction of macrophage infiltration affected livers. Importantly, zinc selectively inhibited M1 macrophage polarization and M1-related inflammatory cytokines. This inhibitory effect was further confirmed by the reduction of relevant biomarkers of M1 macrophages including inducible NO synthase (iNOS), monocyte chemotactic protein-1 (MCP-1/CCL2), and tumor necrosis factor-α in the zinc supplemented BDL livers. In addition, zinc inhibition of M1 macrophages was associated with a decrease of Notch1 expression. Taken together, these data indicated that zinc supplementation inhibited liver inflammation and fibrosis in BDL mice through selective suppression of M1 macrophages, which is associated with inhibition of Notch1 pathway in M1 macrophage polarization.

Adherence to Nutritional Supplementation Determines Postoperative Vitamin D Status, but Not Levels of Bone Resorption Marker, in Sleeve-Gastrectomy Patients.

BACKGROUND: Taking advantage of isomeric form of vitamin E in the supplement, adherence to supplement could be evaluated by changes in circulating α- and γ-tocopherol concentrations. Accordingly, effects of supplementation on postoperative nutrition and bone metabolism were studied in terms of adherence. METHODS: Thirty-eight SG patients were all prescribed a postoperative nutritional supplement containing a low dose of vitamin D (600 IU) and calcium (200 mg). Blood samples were collected prior to (M0) and 6 months after (M6) surgery and concentrations of nutrients and C-terminal telopeptide of type I collage (CTX), a marker of bone resorption, were measured. Adherence and non-adherence were stratified according to change (△, M6-M0) in serum α-tocopherol concentrations (> 0 vs. ≤ 0, respectively). RESULTS: When M0 and M6 were compared, there were significant increases in serum concentrations of 25(OH)D, α-tocopherol and selenium, whereas there were reductions in parathyroid hormone, ferritin, and γ-tocopherol. At M6, the prevalence of vitamin D insufficiency (25(OH)D < 30 ng/mL) and high CTX were 72 and 26%, respectively. When comparison was made between adherence and non-adherence, only △25(OH)D concentrations, but no other nutrients nor postoperative CTX differed. Multiple linear regression demonstrated that postoperative vitamin D status was independently associated with its preoperative concentrations (ß = 0.85, p < 0.001) and adherence (ß = 0.52, p < 0.05). CONCLUSION: SG patients' adherence to supplementation, even with a low dose of vitamin D and calcium, determined vitamin D status but not bone resorption marker concentrations, at least within 6 months after surgery.

Melatonin for an obese child with MC4R gene variant showing epilepsy and disordered sleep: A case report.

BACKGROUND: Abnormalities in the melanocortin receptor 4 (MC4R) gene often lead to obesity, but are rarely associated with other conditions such as epilepsy and sleep disorder. CASE SUMMARY: Here, we present a case of a male obese child with a heterozygous variant in MC4R (c.494G>A, p.Arg165Gln) inherited from his father, who presented with disordered sleep and abnormal facial movements. Examination through melatonin rhythm testing and electroencephalography led to a diagnosis of sleep disorder and epilepsy, as his melatonin rhythm was markedly distorted and the electroencephalography revealed epileptic discharges. He received treatment with an antiepileptic drug; however, the therapy was ineffective and the sleep disorder appeared to be deteriorating. Subsequently, we initiated adjuvant treatment with melatonin. Upon re-examination, his body mass index had decreased, the sleep disturbance had resolved, and his seizures were well controlled. Electro-encephalography review was normal, and a typical melatonin rhythm was restored. CONCLUSION: We concluded that, in addition to causing obesity, abnormalities in the MC4R gene may contribute to the development of sleep disorders and epilepsy, and that melatonin can be used as an adjuvant therapy to alleviate these symptoms.

Targets and underlying mechanisms related to the sedative and hypnotic activities of saponin extracts from semen Ziziphus jujube.

Semen Ziziphus jujube (SZJ) has been widely consumed because it is recognized as edible in China to treat insomnia disorders. However, the underlying mechanisms and potential therapeutic targets remain obscure. SZJ-I and SZJ-II with a saponin content of 52.10% and 75.20%, respectively, were extracted from SZJ. LC-MS analysis presented quite different chemical profiles of SZJ-I and SZJ-II. Mice with p-chlorophenylalanine (PCPA)-induced insomnia were used to comparatively and systematically test the sedative-hypnotic activities of SZJ-I and SZJ-II. In vivo behavioral tests revealed that SZJ-I and SZJ-II significantly shortened the immobility time and potentiated sodium pentobarbital-induced sleep. SZJ-II with a higher saponin content showed greater potency than SZJ-I. SZJ-I and SZJ-II also protected against PCPA-triggered neuropathological damages in the brain. Concentrations of 5-hydroxytryptamine (5-HT), dopamine (DA), noradrenaline (NE), glutamate (Glu), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), nitric oxide (NO) and prostaglandin D2 (PGD2) in plasma were significantly affected by SZJ-I and SZJ-II application. SZJ-I and SZJ-II also exhibited differential modulation of 5-hydroxytryptamine 1A (5-HT1A), 5-hydroxytryptamine 2A (5-HT2A), GABAA receptor α2 (GABAARα2), GABAA receptor α3 (GABAARα3), glutamic acid decarboxylase (GAD) 65/67, IL-6 and IL-1ß expression in the hypothalamus and hippocampus. SZJ-I and SZJ-II might exert excellent sedative-hypnotic effects through multiple mechanisms that worked simultaneously. SZJ-I and especially SZJ-II are promising candidates for relieving insomnia.

Assessing the effectiveness of mindfulness-based programs on mental health during pregnancy and early motherhood - a randomized control trial.

BACKGROUND: The process of entering motherhood is highly stressful for women, with 15-85% of new mothers experiencing postpartum blues or depression. This study was designed to evaluate the efficacy of a mindfulness-based childbirth and parenting program in improving psychological health during the postpartum period. METHODS: This research was a randomized controlled trial with single blinding. Recruitment began after the participating hospital granted formal approval. A total of 74 women between 13 and 28-weeks gestation were allocated either to the intervention group or to the comparison group. The intervention program included a series of eight, 3-h classes held once weekly and 1 day of 7-h silent meditation. Psychological health was assessed at baseline and 3-months postpartum. RESULTS: Significant differences in stress and depression were observed in both groups over time. Stress scores and depression scores were significantly better in the intervention group than in the comparison group at 3-months postpartum (F = 7.19, p = .009 and F = 7.36, p = .008, respectively). No significant difference between the groups was identified for mindfulness scores at 3-months postpartum. CONCLUSIONS: The intervention program effectively reduced postpartum self-perceived stress and depression, suggesting that this program provides acceptable and long-term benefits to women during pregnancy and the postpartum period. The teaching and practice of mindfulness meditation and parenting education during pregnancy may help reduce stress and depression in pregnant women as they transition into parenthood. TRIAL REGISTRATION: The ClinicalTrials.gov identifier for this study is: NCT03185910 . The study was retrospectively registered on 14 June 2017.

LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway.

BACKGROUND: An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play essential roles in tumor initiation and progression. LncRNAs act as tumor promoters or suppressors by targeting specific genes via epigenetic modifications and competing endogenous RNA (ceRNA) mechanisms. In this study, we explored the function and detailed mechanisms of long intergenic nonprotein coding RNA 673 (LINC00673) in breast cancer progression. METHODS: Quantitative real-time PCR (qRT-PCR) was used to examine the expression of LINC00673 in breast cancer tissues and in adjacent normal tissues. Gain-of-function and loss-of function experiments were conducted to investigate the biological functions of LINC00673 in vitro and in vivo. We also explored the potential role of LINC00673 as a therapeutic target using antisense oligonucleotide (ASO) in vivo. RNA sequencing (RNA-seq), dual-luciferase reporter assays, chromatin immunoprecipitation (ChIP) assay, and rescue experiments were performed to uncover the detailed mechanism of LINC00673 in promoting breast cancer progression. RESULTS: In the present study, LINC00673 displayed a trend of remarkably increased expression in breast cancer tissues and was associated with poor prognosis in breast cancer patients. Importantly, LINC00673 depletion inhibited breast cancer cell proliferation by inhibiting the cell cycle and increasing apoptosis. Furthermore, ASO therapy targeting LINC00673 substantially suppressed breast cancer cell proliferation in vivo. Mechanistically, LINC00673 was found to act as a ceRNA by sponging miR-515-5p to regulate MARK4 expression, thus inhibiting the Hippo signaling pathway. Finally, ChIP assay showed that the transcription factor Yin Yang 1 (YY1) could bind to the LINC00673 promoter and increase its transcription in cis. CONCLUSIONS: YY1-activated LINC00673 may exert an oncogenic function by acting as a sponge for miR-515-5p to upregulate the MARK4 and then inhibit Hippo signaling pathway, and may serve as a potential therapeutic target.

Citrus aurantium L. var. amara Engl. inhibited lipid accumulation in 3T3-L1 cells and Caenorhabditis elegans and prevented obesity in high-fat diet-fed mice.

Natural products with anti-obesity effects and few side effects have attracted great attention recently. Citrus aurantium L. var. amara Engl. (CAVA) is popularly consumed as an edible and medicinal resource in China. However, its anti-obesity effects were poorly understood. The anti-obesity effects of CAVA extracts were systematically evaluated using 3T3-L1 cells, Caenorhabditis elegans (C. elegans) and high fat diet (HFD)-fed mice. Flavonoid-rich (EA) extracts with neohesperidin, hesperidin and naringin comprising 32.15%, were isolated from CAVA. EA extracts treatment significantly inhibited differentiation of 3T3-L1 preadipocytes by modulating lipid metabolism-related mediators. EA extracts supplementation also inhibited antioxidant responses in C. elegans by decreasing reactive oxygen species generation and malonaldehyde value, and increasing superoxide dismutase content. EA extracts feeding markedly decreased triglyceride (TG) content, and affected expression of genes involved in lipid and glucose metabolism in wild type C. elegans. TG content in mdt-15 (XA7702) mutants was not decreased by EA extracts administration, suggesting that EA extracts treatment might inhibit lipid accumulation in C. elegans dependent on mdt-15. EA extracts intervention further reduced body weight gain and modulated plasma biochemical parameters in HFD-fed mice. EA extracts treatment prevented HFD-induced epididymal adipose hypertrophy, liver oxidative injuries and steatosis. EA extracts administration also strongly prevented HFD-induced reduction of gut microbial diversity, decreased the Firmicutes-to-Bacteroidetes ratio and the Erysipelotrichaceae abundance, and enhanced the Bifidobacteriace abundance in HFD-fed mice. EA extracts from blossoms of CAVA were excellent antiobesogenic candidates that acted through multiple mechanisms that acted simultaneously.

"Brain Connectivity Deviates by Sex and Hemisphere in the First Episode of Schizophrenia"-A Route to the Genetic Basis of Language and Psychosis?

Schizophrenia is genetic in origin and associated with a fecundity disadvantage. The deficits in schizophrenia have been attributed to variation related to the human capacity for language or brain laterality. How sex influences the relative connectivity of the 2 hemispheres is a route to understanding these 2 functions. Using resting-state functional magnetic resonance imaging (fMRI) we searched for sex- and hemisphere-specific changes in whole-brain functional-connectivity in multi-site datasets (altogether 672 subjects including 286 patients, all right-handed) in the first-episode schizophrenia (illness duration ≤ 1 year, mostly drug naive) and in chronic stages of schizophrenia (illness duration > 1 year), respectively. We used meta-analyses to integrate data from different sources concerning individuals at the same illness stage. We found first-episode male patients are predominantly left-lateralized in aberrant connectivity with a focus on Broca's area. Female patients show a lesser degree of lateralization than males, but to the right particularly in orbital frontal cortex. In the chronic stage, the focus of aberrant connectivity shifted from anterior to posterior structures with prominent involvement of the thalamus and pre- and post-central gyri bilaterally and in both sexes. While the "deviant connectivity" is right-sided in both the first-episode and the chronic stages in females, in males there is a shift between stages from the left to the right hemisphere. We hypothesized that the pathophysiology of schizophrenia may lie in the interaction between sex and lateralization, ie, in genetic mechanisms located on the X and Y chromosomes, intrinsic to the evolution of language.

Mindfulness-based programme on the psychological health of pregnant women.

PROBLEM: Preparation of psychological well-being is an important component of antenatal education for childbirth, but few courses focus on this component. BACKGROUND: The psychosocial health of pregnant women is known to affect perinatal outcomes. Psychosocial stress in women has been associated with increased obstetric interventions and has been shown to affect the health of both mother and child. AIM: To explore the efficacy of an eight-week Mindfulness-Based Childbirth and Parenting programme on reducing prenatal stress, depression, mindfulness, and childbirth self-efficacy. METHODS: In this prospective and randomized controlled trial study, 104 women between 13 and 28 weeks gestation were enrolled and assigned randomly into two groups. Participants in the experimental group received mindfulness-based programme and practice-at-home with audio recordings. The comparison group received traditional education classes. Psychological health was assessed at baseline, post-intervention, and 36-week gestation. FINDINGS: Significant differences were seen in both groups in terms of changes over time in stress, depression, childbirth self-efficacy, and mindfulness, as compared with baseline. In gestation week 36, stress scores were slightly higher and childbirth self-efficacy and mindfulness scores were lower for both groups, but all scores were relatively better in the experimental than in the comparison group. CONCLUSIONS: Perinatal mental health problems affect mothers, their infants, and society. The eight-week mindfulness programme effectively reduced self-perceived stress and depression and increased childbirth self-efficacy and mindfulness. Future research is needed to explore the potential benefits, mechanisms, and effects on maternal and infant birth outcomes of mindfulness.