Efficacy of electrical cranial stimulation for treatment of psychiatric symptoms in patients with anxiety: A systematic review and meta-analysis.

Background: Therapeutic effects of electrical cranial stimulation (CES) in patients suffering from anxiety remained unclear. This meta-analysis aimed at investigating acceptability and therapeutic efficacy of CES against anxiety, depression, and insomnia for patients who experienced symptoms of anxiety. Methods: Major electronic databases were searched from inception until December 10, 2022 for randomized controlled trials (RCT) focusing on therapeutic effectiveness of CES in patients whose primary complaints included anxiety. Effect sizes (ES) for different treatment outcomes were estimated by using generic inverse variance method. Results: Eight RCTs were identified including a total of 337 participants. The therapeutic effectiveness of CES was significantly better than that in the control groups for anxiety (ES=-0.96, p <0.00001, eight trials, 337 patients), depression (ES=-0.69, p=0.003, five trials), and insomnia (ES=-1.02, p = 0.0006, three trials) in those who presented with symptoms of anxiety. Subgroup analyses found that CES was equally effective regardless of comorbid presentation of depressive symptoms (ES=-0.94 in patients with anxiety only vs. ES=-1.06 in those with depression and anxiety) and whether CES was used as monotherapy or add-on therapy to medications (ES = -0.88 vs. ES = -1.12, respectively). Moreover, subgroup analysis of RCTs using the same device "Alpha-Stim" for CES was more effective in alleviating anxiety than sham controls (ES = -0.88, p < 0.00001, four trials, 230 patients). Regarding acceptability, the use of CES did not increase the risk of treatment-related dropout compared to the control group (RR = 1.26, p = 0.57, I2 = 0%, four trials, 324 patients). Conclusion: Our study supported the use of CES for symptoms of anxiety, depression, and insomnia in those suffering from anxiety with fair acceptability and demonstrated the efficacy of "Alpha-Stim", the most commonly used device for CES, in this patient population. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022382619.

Salidroside ameliorates pathological cardiac hypertrophy via TLR4-TAK1-dependent signaling.

Salidroside, a prominent active ingredient in traditional Chinese medicines, is garnering increased attention because of its unique pharmacological effects against ischemic heart disease via MAPK signaling, which plays a critical role in regulating the evolution of ventricular hypertrophy. However, the function of Salidroside on myocardial hypertrophy has not yet been elucidated. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with Salidroside (100 mg kg-1  day-1 ) by oral gavage for 3 weeks starting 1 week after surgery. Four weeks after TAC surgery, the mice were subjected to echocardiography and then sacrificed to harvest the hearts for analysis. For in vitro study, neonatal rat cardiomyocytes were used to validate the protective effects of Salidroside in response to Angiotensin II (Ang II, 1 µM) stimulation. Here, we proved that Salidroside dramatically inhibited hypertrophic reactions generated by pressure overload and isoproterenol (ISO) injection. Salidroside prevented the activation of the TAK1-JNK/p38 axis. Salidroside pretreatment of TAK1-inhibited cardiomyocytes shows no additional attenuation of Ang II-induced cardiomyocytes hypertrophy and signaling pathway activation. The overexpression of constitutively active TAK1 removed the protective effects of Salidroside on myocardial hypertrophy. TAC-induced increase of TLR4 protein expression was reduced considerably in the Salidroside treated mice. Transient transfection of small interfering RNA targeting TLR4 (siTLR4) in cardiomyocytes did not further decrease the activation of the TAK1/JNK-p38 axis. In conclusion, Salidroside functioned as a TLR4 inhibitor and displayed anti-hypertrophic action via the TAK1/JNK-p38 pathway.

The effectiveness of child-centered play therapy for executive functions in children with attention-deficit/hyperactivity disorder.

INTRODUCTION: Child-centered play therapy (CCPT) is a practical and recommended non-medication intervention for children with Attention-deficit/hyperactivity disorder (ADHD) but the mechanism in between is unclear. AIM: This study proposed to examine the effectiveness of CCPT on neuropsychological deficits and behavioral symptoms in ADHD. METHODS: Participants with ADHD diagnosis were referred from senior child and adolescent psychiatrists, and typical developmental children (TD) were recruited from community as a control group. All participants' executive functions were evaluated using Cambridge Neuropsychological Test Automated Battery. First of all, the participants were evaluated using Child Behavior Checklist (CBCL) by their parents. The ADHD participants were assigned into CCPT (ADHDc) and waitlist (ADHDw) group; and the ADHDc group then received CCPT weekly for 12 sessions, while the ADHDw continuously received their regular treatment (i.e., medication treatment or other alternative treatments) as usual. RESULTS: Total 52 participants were recruited (17 with ADHD and 35 typically developed children, TD). The results showed that overall the ADHD groups had worse neuropsychological performance and more behavioural disturbance than did the TD (ps < .05). After receiving the CCPT, the results showed that the ADHDc group had significant improvement in the cognitive flexibility (p < .05); while the ADHDw group had no changes.

Additive effects of EEG neurofeedback on medications for ADHD: a systematic review and meta-analysis.

To elucidate possible additive effects of electroencephalogram-based neurofeedback (EEG-NF) on medications against the core symptoms of attention-deficit/hyperactivity disorder (ADHD), randomized controlled trials (RCTs) were retrieved from electronic databases including PubMed, EMBASE, ClinicalKey, Cochrane CENTRAL, ScienceDirect, and ClinicalTrials.gov from inception to March 2022. The primary outcomes were changes in ADHD symptoms (i.e., global, inattention, hyperactivity/impulsivity) assessed with validated rating scales, while secondary outcome was all-cause discontinuation rate. Meta-analysis of five RCTs involving 305 participants [Median age = 9.285 years (range 8.6-11.05)] with a median follow-up of 12 weeks showed additive effects of EEG-NF on medications from parents' observations against ADHD global symptoms (Hedges' g = 0.2898, 95%CI [0.0238; 0.5557]) and inattention symptoms (Hedges' g = 0.3274, 95%CI [0.0493; 0.6055]). However, additive effects failed to sustain six months after EEG-NF intervention. Besides, there was no difference in improvement of hyperactivity/impulsivity from parents' observation, attentional performance, and all-cause discontinuation rate between the two groups. Our results supported additional benefits of combining EEG-NF with medications compared to medication alone in treating global symptoms and symptoms of inattention in ADHD patients. Nevertheless, given a lack of evidence showing a correlation between underlying physiological changes and small effect sizes in our preliminary results, further studies are warranted to support our findings.

Effects of Yi-Gan-san on the psychiatric behavior of children and adolescents with Tourette's Syndrome: A randomized, double-blind, controlled preliminary study.

ETHNOPHARMACOLOGICAL RELEVANCE: Gilles de la Tourette's Syndrome (TS) is a childhood-onset disease with clinical features of motor and phonic tics. Yi-Gan-san (YGS) is a traditional Chinese medicine formula that can reduce aggressiveness and agitation and inhibit dopamine function. This study investigated the effects of YGS on the psychiatric behavior of children and adolescents with TS. METHODS: A double-blind, randomized, controlled preliminary study was conducted. A total of 38 patients with TS were assigned to the control group (CG, 19 patients) who received the oral administration of YGS placebo (90% starch and 10% YGS; 2.5 g thrice daily) or to a treatment group (TG, 19 patients) who received YGS for 4 weeks. The primary outcome measure was the change in Yale Global Tic Severity Scale (YGTSS) overall and subscale scores. RESULTS: The intensity score for phonic tics before oral administration of YGS, and after 2 weeks, 3 weeks and 4 weeks was not significantly different between CG and TG groups (2.94 ± 1.14 vs 2.79 ± 1.08, p = .686; 2.29 ± 1.21 vs 1.95 ± 1.08, p = .370; 2.41 ± 1.18 vs 2.05 ± 1.51, p = .435; and 2.29 ± 1.26 vs 1.84 ± 1.42, p = .323, respectively), while the intensity score for phonic tics after 1-week oral administration of YGS in the TG was 1.89 ± 1.10 lower than 3.06 ± 1.39 in the CG (p = .008). CONCLUSION: Oral administration of YGS for 1 week only reduced the intensity of phonic tics compared with oral administration of YGS placebo, suggesting that YGS can reduce their intensity for a short period, and the compliance of oral administration of YGS for 4 weeks can be accepted in children and adolescents with Tourette's Syndrome. However, because this study was preliminary, the selection of an appropriate placebo and dosage and long-term observations are crucial areas for future studies.

6-Gingerol protects against cardiac remodeling by inhibiting the p38 mitogen-activated protein kinase pathway.

6-Gingerol, a pungent ingredient of ginger, has been reported to possess anti-inflammatory and antioxidant activities, but the effect of 6-gingerol on pressure overload-induced cardiac remodeling remains inconclusive. In this study, we investigated the effect of 6-gingerol on cardiac remodeling in in vivo and in vitro models, and to clarify the underlying mechanisms. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 6-gingerol (20 mg/kg, ig) three times a week (1 week in advance and continued until the end of the experiment). Four weeks after TAC surgery, the mice were subjected to echocardiography, and then sacrificed to harvest the hearts for analysis. For in vitro study, neonatal rat cardiomyocytes and cardiac fibroblasts were used to validate the protective effects of 6-gingerol in response to phenylephrine (PE) and transforming growth factor-ß (TGF-ß) challenge. We showed that 6-gingerol administration protected against pressure overload-induced cardiac hypertrophy, fibrosis, inflammation, and dysfunction in TAC mice. In the in vitro study, we showed that treatment with 6-gingerol (20 µM) blocked PE-induced-cardiomyocyte hypertrophy and TGF-ß-induced cardiac fibroblast activation. Furthermore, 6-gingerol treatment significantly decreased mitogen-activated protein kinase p38 (p38) phosphorylation in response to pressure overload in vivo and extracellular stimuli in vitro, which was upregulated in the absence of 6-gingerol treatment. Moreover, transfection with mitogen-activated protein kinase kinase 6 expressing adenoviruses (Ad-MKK6), which specifically activated p38, abolished the protective effects of 6-gingerol in both in vitro and in vivo models. In conclusion, 6-gingerol improves cardiac function and alleviates cardiac remodeling induced by pressure overload in a p38-dependent manner. The present study demonstrates that 6-gingerol is a promising agent for the intervention of pathological cardiac remodeling.

[Effect of Montmorillonite on Fractions and Availability of Phosphorus in Soils Applied with Organic Fertilizer].

An incubation experiment was carried out to study the effect of montmorillonite on pH, the fractions and availability of phosphorus in a sandy yellow soil (SY) and a mineral flavicant soil (MF) applied with biogas residues of swine manure (BSR). The rates of montmorillonite applied were 0%, 5%, 7.5% and 10%, respectively. The results indicated that soil pH was not affected by BSR, but was significantly increased by montmorillonite. In both soils, application of BSR caused an increase in the content and proportion of Al-P during the incubation, and an increase in the content but a slight decrease in the proportion of Fe-P in later period of incubation. The concentration of O-P was not markedly changed, but its proportion was decreased by applying BSR in both soils. The changes of Ca-P varied with soils. BSR had no significant influence on Ca-P content, but decreased the proportion of Ca-P in SY, meanwhile, it increased both Ca-P content and proportion in MF. Addition of montmorillonite in soils applied with BSR decreased the contents and proportions of Al-P and O-P, and the proportion of Fe-P did not change the contents of Fe-P, but increased the content and proportion of Ca-P in SY. In MF, montmorillonite could decrease the contents and proportions of Fe-P and O-P, and the proportion of Al-P did not affect the content of Al-P, but increased the contents and proportions of Ca-P greatly. The contents of available phosphorus (A-P) were enhanced by 17.9%-38.0% and 17.1%-33.7% in SY and MF respectively, and the phosphorus activation coefficient (PVC) was significantly improved in both soils by applying BSR. The contents of A-P were reduced by 8.8%-35.5% and 1.1%-11.6% in SY and MF respectively. Correlation analysis showed that montmorillonite reduced the availability of phosphorus through increasing pH and contents of Ca-P, decreasing the content of Al-P in SY, and through increasing pH and decreasing content of Fe-P in MF. The availability of phosphorus in SY was influenced more obviously than that in MF by montmorillonite.