Efficacy of tDCS to enhance virtual reality exposure therapy response in acrophobia: A randomized controlled trial.

[BACKGROUND]: Virtual reality exposure therapy (VRET) has been recognized as an effective treatment for specific phobias and has the potential to overcome the limitations of traditional exposure therapy. The pursuit of non-invasive brain stimulation provides a practical means of augmenting VRET. Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique, stimulates the medial prefrontal cortex (mPFC), with the potential to enhance the effects of exposure therapy. Therefore, we conducted a randomized controlled trial to examine whether tDCS enhanced the effects of VRET in acrophobia. [METHOD]: This study recruited 64 college students with significant fear of height (based on the Acrophobia Questionnaire, AQ). Finally, 61 participants were randomly allocated to the tDCS active-stimulated group (n = 30) or the sham-stimulated group (n = 31). After stimulation, VRET was conducted, and clinical indices were recorded. The AQ was used as the first primary outcome, and Subjective Units of Distress (SUDS) and the Heights Interpretation Questionnaire (HIQ) were used as secondary outcomes. [RESULT]: There was a significant reduction in psychometric and behavioral anxiety measurements from pre to post treatment as indicated by main effects for the factor time (AQ-Anxiety: F (2.60) = 139.55, p < 0.001, η2 = 0.83; AQ-Avoidance: F (2.60) = 53.73, p < 0.001, η2 = 0.69; HIQ: F (2.60) = 128.12, p < 0.001, η2 = 0.81; STAI-Y-S: F (2.60) = 15.44, p < 0.001, η2 = 0.34; BAI: F (2.60) = 73.81, p < 0.001, η2 = 0.71). Compared with the sham-stimulated group, the reduction of AQ-Anxiety and SUDS in the first exposure trial (F (2,60) = 8.56, p = 0.001, η2 = 0.23; t = 2.34, p = 0.024, d = 0.61) was significantly faster in the active group. At follow-up, there was also a further reduction in AQ anxiety and avoidance (Anxiety: M = 56.51 ± 27.19; main effect time F (1,60) = 25.16, p < 0.001, η2 = 0.35; Avoidance: M = 12.57 ± 7.97; main effect time F (1,60) = 31.40, p < 0.001, η2 = 0.45) without interaction time*group (Anxiety: F (1.60) = 0.12, p = 0.740, η2 = 0.00; Avoidance: F (1.60) = 0.64, p = 0.430, η2 = 0.02). [CONCLUSION]: Results could be explained tDCS could accelerate the effects of VRET on acrophobia by stimulating mPFC, indicating that tDCS may be used as an enhancement technique for exposure therapy for specific phobias.

How does centralized isolation treatment strategy affect the medical staff's mental health during the COVID-19 pandemic?

Background: During the coronavirus 2019 (COVID-19) pandemic, the Chinese Government adopted a centralized isolation treatment (CIT) strategy for patients, which has greatly improved the efficiency of the pandemic response. However, compared to those in local hospitals, anti-COVID-19 medical staff in mobile cabin hospitals, where the CIT strategy was adopted, suffered more mental health problems. This study aimed to explore how the CIT strategy affected the medical staff's mental health by comparing anti-COVID-19 medical staff who worked in mobile cabin hospitals to those in fever clinics of local hospitals. Methods: Following the standard scale development procedure, this study first developed a scale measuring the mental health of anti-COVID-19 medical staff. Using SPSS 23.0 and Amos 23.0 software, the exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and reliability analysis method were conducted to support the scale development. In the main investigation, a survey method using the developed scale was used, and 839 anti-COVID-19 medical staff from five hospitals in northern China were recruited as participants by snowball-sampling method. The first survey was conducted in February 2020, when the first round of COVID-19 was at a serious time. In April 2020, after the first round of COVID-19 in China was initially contained, and medical staff who worked in mobile cabin hospitals returned to local hospitals, a follow-up survey was conducted on these participants. Using SPSS 23.0 software, a series of 2 × 2 mixed-design ANOVA was conducted, in which working conditions (mobile cabin hospital vs. local hospital) served as a between-subject factor, time points (during vs. after the first round of COVID-19) served as a within-subject variable, and the indicators of the medical staff's mental health served as dependent variables respectively. Results: The reliability and validity of the developed scale were desirable. The mental health problems of anti-COVID-19 medical staff were mainly manifested as anxiety, powerlessness, fear of infection, and somatization. Compared to those who worked in local hospitals, anti-COVID-19 medical staff who worked in mobile cabin hospitals where the CIT strategy was adopted suffered more powerlessness, fear of infection, and somatization. After returning to local hospitals, symptoms of fear of infection and powerlessness of medical staff who used to work in mobile cabin hospitals decreased significantly. However, their anxiety symptoms were not relieved, and their somatization symptoms even increased. Conclusion: This study implied that the mental health of anti-COVID-19 medical staff in mobile cabin hospitals adopting CIT was worse than in local hospitals. Moreover, with the first outbreak in remission, the mental health recovery of medical staff in CIT hospitals was slower than in local hospitals. Relevant practitioners should pay more attention to the mental health condition of anti-COVID-19 medical staff who work in CIT hospitals. The psychological assistance service for them should continue even after they return to the local hospitals.

Ginsenoside Ro Ameliorates High-Fat Diet-Induced Obesity and Insulin Resistance in Mice via Activation of the G Protein-Coupled Bile Acid Receptor 5 Pathway.

Obesity, a well known risk factor in multiple metabolic diseases, is dramatically increasing worldwide. Ginsenosides extracted from ginseng have been reported against obesity and the associated metabolic disorders. As a subtype of ginsenoside, ginsenoside Ro is a critical constituent of ginseng. However, its specific effects on obesity remain unknown. G protein-coupled bile acid receptor 5 (TGR5) (also known as GPBAR1) is a bile acid membrane receptor, widely expressed in human tissues contributing to various metabolic processes to confer the regulations of glucose and lipid homeostasis. TGR5 has displayed potential as a therapeutic target for the treatment of metabolic disorders. Here, we explore the antiobesity effect of ginsenoside Ro with TGR5 activation screened by a library of natural products. Our results showed that the ginsenoside Ro (90mg/kg) treatment ameliorated body weight and lipid accumulation in multiple metabolic organs of high-fat diet-induced obese (DIO) mice without affecting food intake and improved oral glucose tolerance tests, intraperitoneal insulin tolerance tests, and fasting serum glucose. We also found that triglyceride and total cholesterol in serum and liver were significantly decreased after ginsenoside Ro treatment. Then we used Tgr5 knockout mice to explore the role of Tgr5 in the antiobesity effect of ginsenoside Ro. Our results further demonstrated that ginsenoside Ro promoted glucagon-like peptide 1 (GLP-1) secretion and energy expenditure in wild-type DIO mice. However, the stimulation of ginsenoside Ro on GLP-1 secretion and energy expenditure were restrained in the Tgr5 knockout mice. In conclusion, our findings demonstrated that ginsenoside Ro ameliorates obesity and insulin resistance in DIO mice via activating TGR5, indicating a potential therapeutic role of ginsenoside Ro to treat obesity and its associated metabolic diseases. SIGNIFICANCE STATEMENT: Obesity is dramatically increasing worldwide, and it contributes to multiple metabolic diseases. G protein-coupled bile acid receptor 5 (TGR5) is a potential therapeutic target for the treatment of metabolic disorders. Ginsenoside Ro, as an oleanane-type ginsenoside, ameliorates obesity and insulin resistance, promotes glucagon-like peptide 1 secretion, and increases energy expenditure via activating TGR5. Ginsenoside Ro could be a potential leading compound for treating obesity and its associated metabolic diseases.

Quality of life among primary and middle school students and its association with negative emotions and social support in Henan Province / 中国学校卫生

Objective@#To understand the current status of health related quality of life among primary and middle school students aged 9 to 15 years old in Henan Province, and to explore its relationship with negative emotions and social support.@*Methods@#Between January and June 2016, 24 primary and middle schools were selected from 6 cities of Henan Province, and 5 867 primary and middle school students were included and completed the Pediatric Quality of Life Inventory Measurement, Stress Anxiety Depression Scale, Perceived Social Support Scale. Hierarchical linear regression analysis was used to examine the moderating effect of social support.@*Results@#The total score of health related quality of life of primary and middle school students in Henan was (81.21±12.49). There were statistically significant differences in the quality of life among primary and middle school students with different gender, study period, family monthly income, subjective parental relationship and parental education ( P <0.05). Negative emotions were negatively correlated with quality of life ( r =-0.51, P <0.01) and social support ( r =-0.30, P <0.01), while social support was positively correlated with quality of life ( r =0.29, P <0.01). Regression analysis showed that negative emotional was negatively associated with quality of life ( β =-0.23, P <0.01), while social support was positively associated with quality of life ( β =0.16, P <0.01). The interaction of negative emotions and social support was negatively associated with quality of life ( β =-0.18, P <0.01).@*Conclusion@#Health related quality of life among 9-15 year old primary and middle school students in Henan province is satisfactory. Social support might buffer the negative impact of negative emotions including depression, anxiety and stress on quality of life of primary and secondary school students.

Anxiety life interference among primary and middle school students in Henan Province and its influencing factors / 中国学校卫生

Objective@#To investigate anxiety life interference among primary and middle school students in Henan Province and its influencing factors, and to provide scientific basis for health education in primary and secondary school students.@*Methods@#By using cluster sampling method, 3 573 primary school students and 2 748 secondary school students in Henan Province were investigated with Child Anxiety Life Interference Scale(CALIS), Resilience Scale for Chinese Adolescents(RSCA), Perceived Social Support Scale(PSSS), Self-Esteem Scale(SES), General Self-efficacy Scale(GSES).@*Results@#There were significant differences in anxiety life disturbance in primary and middle school students by gender(t=2.07, P=0.04), school level(t=-2.29, P=0.02), degree of anxiety(F=119.93, P<0.01), educational level of fathers (F=13.38, P<0.01) and educational level of mothers(F=9.65, P<0.01). The degree of life disturbance caused by anxiety was negatively correlated with mental resilience, social support and self-efficacy(r=-0.25, -0.09, -0.12, P<0.01), and was positively related to self-esteem(r=0.23). Mental resilience (β=-0.21) significantly negatively predicted anxiety interference with life, while self-esteem (β=0.13) and social support (β=0.06) significantly positively predicted anxiety interference with life.@*Conclusion@#The life of primary and middle school students is seriously disturbed by anxiety, and mental resilience is the primary psychosocial factor that affects the level of anxiety life interference among primary and middle school students.

Pharmacokinetics, Tissue Distribution, and Metabolism Study of Icariin in Rat.

Icariin is one of the predominant flavonoids contained in Herba Epimedii (Yin-yang-huo in Chinese), a well-known Chinese medicine for the treatment of cancers and immune system diseases. Although Herba Epimedii has been widely used in China and there are so many and various research reports on the herbal drug and its main flavones, very limited data is available on the tissue distribution and biotransformation of icariin. In the present study, a liquid chromatographic method combined with electrospray ionization tandem mass spectrometry was developed to quantify the concentration of icariin in rat plasma and various tissues collected at different time points after oral administration of the total flavonoid extract of Herba Epimedii at a dose of 0.69 g/kg (corresponding to 42 mg/g icariin). Biological samples were processed by simple protein precipitation. Genistein was chosen as internal standard. The method was successfully applied to plasma pharmacokinetic and tissue distribution studies of icariin in rat. As a result, it was worth noting that the tissue distribution characteristics of icariin exhibited a significant gender difference. Moreover, in vivo metabolism of icariin was also investigated. A total of 11 potential metabolites were found in rat feces collected in different time periods after oral and intramuscular administration of icariin. In vivo metabolic pathways were involved in hydrolysis, demethylation, oxidation, and conjugation. The preclinical data would be useful for fully understanding in vivo disposition of this compound and interpreting the mechanism of its biological response.

Determination of Epimedin B in Rat Plasma and Tissue by LC-MS/MS: Application in Pharmacokinetic and Tissue Distribution Studies.

A simple, sensitive, and specific liquid chromatography tandem mass-spectrometric method was developed and validated for the determination of epimedin B in rat plasma and tissue samples. After being processed with a protein precipitation method, these samples were separated on an Agilent Eclipse XDB-C18 column with an isocratic mobile phase consisting of acetonitrile and 0.1% formic acid aqueous solution (32 : 68, v/v). The calibration curve of epimedin B was linear over the concentration range from 1 to 500 ng/mL in plasma and tissue homogenate. The method was then applied to pharmacokinetic and tissue distribution studies after a single oral administration of Herba Epimedii extract to SD rats. Results showed that epimedin B reached the plasma peak concentration at 0.4 h and the terminal elimination half-life was 1.6 h in rat plasma, and the plasma area under the curve from time zero to infinity (AUC0-∞ ) was 14.35 µg/L·h. The concentration distribution of epimedin B in rat tissue was in the following order: liver > ovary > womb > lung > kidney > spleen > heart > brain, indicating that the compound could be widely distributed in rat, and the reproductive system may be the principal target of epimedin B for female rat.

[In vivo study of Chuankezhi metabolism in rat].

To study the metabolic products of main compounds of Chuankezhi injection in rat, 12 Sprague Dawley rats were classed into 2 groups, a blank control group and an intermuscular administration group, respectively. Rat feces and urine samples were collected from 0−24 h and 24−48 h after administration. All the samples were ultrasonically treated with methanol and then analyzed using LC-LTQ Orbitrap MSn. By comparison with the total ion chromatogram of samples from the blank control group, the metabolites in the samples of drug-treated group were screened. These metabolites were further analyzed by multistage product ion scanning and comparison of retention time with reference substances. As a result, a total of 12 flavonoid metabolites were tentatively identified from the rat feces and no metabolite was discovered in the rat urine. Epimedin C and icariin were detected in the rat blood samples after 30 min of administration, but their metabolites and other original flavones were not detected. Furthermore, no original flavones and their metabolites were detected in rat blood samples after 2 and 4 h of administration. The potential metabolism paths were further characterized and the principal in vivo transformation of flavones from Chuankezhi injection were deglycosylation, dehydration, methylation, oxidation and isomerization in rats.

Comparative Pharmacokinetics and Bioavailability of Epimedin C in Rat after Intramuscular Administration of Epimedin C, a Combination of Four Flavonoid Glycosides and Purified Herba Epimedii Extract.

Chuan-Ke-Zhi (CKZ), a purified Herba Epimedii extract, is a potent Chinese medicine preparation whose main bioactive components are a class of flavonoid glycosides such as epimedins A, B, and C and icariin. And epimedin C is far more abundant than other flavones in this extract. This study aims to investigate the pharmacokinetic and bioavailability of epimedin C and what effects, if any, other ingredients in CKZ have on its pharmacokinetics. Epimedin C, CKZ, and a combination of epimedins A, B, and C and icariin were, respectively, administrated to rats, and then the pharmacokinetic parameters of epimedin C in the three groups were calculated and compared. The result indicated that CLZ, MRT0-∞, and AUC0-∞ of epimedin C were significantly different among the three groups (P < 0.05), and compared with the epimedin C group, the absorption of epimedin C significantly increased in the CKZ group. Furthermore, in this study the absolute bioavailability of epimedin C was also investigated by comparing intramuscular and intravenous administration of epimedin C. As a result, epimedin C could be quickly absorbed with extremely high absolute bioavailability after intramuscular administration.

[Simultaneous determination of 4 prenylflavonoids of Chuankezhi injection in rat plasma by LC-MS/MS].

A quantitative method for epimedin A, B, C and icariin in rat plasma was established using LC-MS/MS after intermuscular administration of Chuankezhi injection to rat. Chromatographic separation was performed on an Agilent Eclipse XDB-C(18) column (150 mm × 2.1 mm, 5.0 µm) at 40 ℃. Mobile phase consisted of acetonitrile-0.1% formic acid in water（35∶65）, and the flow rate was 0.22 m L·min(-1). The LC effluent was detected and analyzed using an ESI-triple quadrupole tandem mass spectrometer under the multiple reaction monitoring (MRM) in the negative ion mode. The plasma samples were treated with solid phase extraction prior to LC-MS/MS analysis. As a result, all of the four analytes displayed a good linearity over the concentration of 1-1 000 ng·mL(-1). The RSDs of intra-day and inter-day assays were less than 5.99% and 10.16%, respectively. The relative recovery of each analyte was between 88.1%-101.1% with RSD < 7.9% and the absolute recovery was between 72.0%-86.6%（RSD < 6.3%）. In conclusion, the established method shows good specificity, sensitivity and efficiency for quantifying the four flavonoid glycosides contained in rat plasma.

[Pharmacokinetics of epimedin A, B, C and icariin of Chuankezhi injection in rat].

To study pharmacokinetic characteristics of epimedin A, B, C and icariin after intermuscular administration of Chuankezhi injection to rat. The established RRLC-MS/MS method was applied for simultaneous determination of four analytes in rat plasma and calculating their pharmacokinetic parameters. As a result, each analyte showed a good linear relationship in the concentration range of 1-1 000 µg•L⁻¹.The intra-day precise was 96.9%-107.5% with RSD<5.99%, inter-day precise was 92.3%-105.0% with RSD<10.16%. The relative recovery of four analytes was 88.1%-101.1% with RSD<7.9% and their absolute recovery was 72.0%-86.6% with RSD<6.3%. After intermuscular administration of Chuankezhi injection, the plasma concentration of four flavonoid glycosides rapidly arose to peaks at about 10 min, and then quickly declined in rat. Tmax of epimedin A, B, C and icariin was 0.21, 0.19, 0.16 and 0.49 h, respectively, and their mean elimination half-life(t1/2z) was 0.60, 0.62, 0.47 and 0.49 h. The established method was validated to be sensitive, rapid and specific for determination of the four analytes. Serum concentration of 4 species of epimedium flavonoids in Chuankezhi injection was low, and their absorption and elimination seem quickly, displaying similar pharmacokinetic characteristics in this study.

[The relationship between the quality and the leaf shape of Magnolia officinalis produced in Hubei enshi].

OBJECTIVE: To reveal the relationship between the quality and the leaf shape of Magnolia officinalis produced in Hubei Enshi. METHODS: Determined the content of magnolol and honokiol by HPLC with methanol-water (78:22) and the detective wavelength was 294 nm. RESULTS: The content of magnolol and honokiol in the leaf of Magnolia officinalis was usually higher if the leaf apex was convex and the leaves were short. In certain years, the content of magnolol and honokiol in Cortex Magnoliae officinalis was positively correlated with the bark thickness. CONCLUSION: The leaf shape of Magnolia officinalis produced in Hubei Enshi is directly related to the phenolic content of leaf itself. But it has nothing to do with the content of magnolol and honokiol in Cortex Magnoliae officinalis.