[Clinical effect of acupuncture based on syndrome differentiation in the treatment of chronic insomnia and its influence on cognitive function].

OBJECTIVE: To compare the effect of acupuncture based on syndrome differentiation and estazolam in the treatment of chronic insomnia and its influence on cognitive function. METHODS: A total of 90 patients with chronic insomnia were randomly divided into an acupuncture group and a medication group, 45 cases in each group. The acupuncture group was treated with acupuncture at Sishencong (EX-HN 1) and bilateral Shenmen (HT 7), Sanyinjiao (SP 6) combined with compatibility of acupoints based on syndrome differentiation, once a day for 6 d and then rest for 1 d, for a total of 4 weeks. The medication group was treated with oral estazolam tablets before bedtime, 1 tablet each time, for a total of 4 weeks. Before and after treatment, the scores of Pittsburgh sleep quality index (PSQI), mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and auditory verbal memory test (AVMT) of the two groups were compared, and the effects were evaluated. RESULTS: After treatment, the PSQI sub-item scores and total scores of the two groups were lower than those before treatment ( P<0.05 ), and above scores in the acupuncture group were lower than those in the medication group ( P<0.05 ); the scores of MMSE, MoCA and AVMT in the two groups were higher than those before treatment ( P<0.05 ), and the scores in the acupuncture group were higher than those in the medication group ( P<0.05 ). The total effective rate of the acupuncture group was 80.0% (36/45), which was higher than 53.3% (24/45) in the medication group (P<0.05). CONCLUSION: Syndrome differentiation acupuncture can improve the sleep quality and cognitive function of patients with chronic insomnia, and the curative effect is better than that of estazolam.

Improved Sleep Affects Epigastric Pain in Functional Dyspepsia by Reducing the Levels of Inflammatory Mediators.

INTRODUCTION: The pathogenesis of epigastric pain in functional dyspepsia (FD) is complex. The study aims to explore the effect of sleep improvement on this symptom. METHODS: In total, 120 patients with FD-associated epigastric pain and insomnia were randomly divided into experimental and control groups using the envelope method. After applying the exclusion criteria, 107 patients were enrolled in the experimental (56 patients) and control (51 patients) groups. Insomnia was graded according to the Pittsburgh Sleep Quality Index (PSQI). In the experimental group, eszopiclone 3 mg, eszopiclone 3 mg + estazolam 1 mg, and eszopiclone 3 mg + estazolam 2 mg were given to patients with mild, moderate, and severe insomnia, respectively. In the control group, patients were given 1, 2, or 3 tablets of vitamin B complex. Patient sleep quality was monitored with Sleepthing. Epigastric pain was evaluated with a Numeric Rating Scale. The serum levels of IL-1ß, IL-6, IL-8, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. Pain scores, sleep parameters, and serum levels of inflammatory mediators were compared before and after treatment. RESULTS: After treatment, the pain scores, sleep parameters, and TNF-α and IL-6 levels in the experimental group were significantly lower than those in the control group (p < 0.05). PSQI insomnia scores were significantly associated with pain scores, IL-6, and TNF-α (p < 0.05) but not in IL-8 and IL-1ß levels (p > 0.05) among the three groups. CONCLUSIONS: Improving sleep with eszopiclone and/or estazolam alleviates FD-associated epigastric pain, possibly by inhibiting related downstream transmission pathways and reducing the release of inflammatory mediators.

Effects of electroacupuncture on the ventral tegmental area- nucleus accumbens dopamine pathway in rats with chronic sleep deprivation.

BACKGROUND: Insomnia is a well-recognized clinical sleep disorder in the adult population. It has been established that acupuncture has a clinical effects in the treatment of insomnia; however, research on the underlying neural circuits involved in these effects is limited. METHODS: The modified multiple platform method (MMPM) was used to establish a rat model of chronic sleep deprivation (CSD). Forty rats were randomly divided into a control (Con) group, (untreated) CSD group, electroacupuncture-treated CSD group (CSD + EA) and estazolam-treated CSD group (CSD + Estazolam group) with n = 10 per group. In the CSD + EA group, EA was delivered at Yintang and unilateral HT7 (left and right treated every other day) with continuous waves (2 Hz frequency) for 30 min/day over 7 consecutive days. In the CSD + Estazolam groups, estazolam was administered by oral gavage (0.1 mg/kg) for 7 consecutive days. The open field test (OFT) was used to observe behavioral changes. Immunofluorescence assays and enzyme-linked immunosorbent assay (ELISA) were used to observe the effects of EA on the ventral tegmental area (VTA)-nucleus accumbens (NAc) dopamine (DA) pathway. We also assessed the effects of EA on the expression of dopamine D1 receptor (D1R) and dopamine D2 receptor (D2R) in the NAc, which are the downstream targets of the VTA-NAc DA pathway. RESULTS: After CSD was established by MMPM, rats exhibited increased autonomous activity and increased excitability of the VTA-NAc DA pathway, with increased VTA and NAc DA content, increased D1R expression and decreased D2R expression in the NAc. EA appeared to reduce the autonomous ability of CSD rats, leading to lower DA content in the VTA and NAc, reduced expression of D1R in the NAc and increased expression of D2R. Most importantly, EA produced effects similar to estazolam with respect to the general condition of rats with CSD and regulation of the VTA-NAc DA pathway. CONCLUSIONS: The therapeutic effect of EA in chronic insomnia may be mediated by reduced excitability of the VTA-NAc DA pathway, with lower DA content in the VTA and NAc, downregulated expression of D1R in the NAc and increased expression of D2R.

[Clinical efficacy of shallow-needle therapy combined with estazolam on insomnia of liver stagnation transforming into fire pattern: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of shallow-needle therapy combined with estazolam on insomnia differentiated as liver stagnation transforming into fire and its effect on adrenocorticotropic hormone (ACTH) and cortisol (CORT), so as to explore the mechanism of this combined treatment. METHODS: A total of 119 patients with insomnia of liver stagnation transforming into fire pattern were randomly divided into shallow-needle therapy group (n=40), medication group (n=39), and shallow-needle therapy combined with medication group (combined therapy group,n=40). In the shallow-needle therapy group, the patients were treated with finger pressure and operation with shallow stimulating at Zhenjing (Dong's extra point, sedative point) and Taichong (LR3). In the medication group, the patients were administered with estazolam (1 mg) orally. In the combined therapy group, both shallow-needle therapy and medication were administered. The treatment was given once daily in each group, 10 days as one session of treatment and 2 sessions were required. Before and after the treatment, Pittsburgh sleep quality index scale (PSQI) and Self-rating anxiety scale (SAS) were used to assess sleep and anxiety status. ELISA was used to detect the contents of ACTH and CORT in plasma. The clinical efficacy was evaluated in each group. RESULTS: In within-group comparison, PSQI scores, SAS scores and the concentrations of ACTH and CORT in plasma were all decreased (P<0.05) after treatment for the patients of three groups. After treatment, the total PSQI score, the score for sleep latency, sleep duration and daytime dysfunction, as well as SAS score in the combined therapy group were all lower than those of the shallow-needle therapy group (P<0.05); the total PSQI score, the score for sleep duration and sleep efficiency, as well as SAS score were lower when compared with the medication group (P<0.05). The total effective rates were 87.50% (35/40), 82.05% (32/39) and 95.00% (38/40) in the shallow-needle therapy group, the medication group and the combined therapy group, respectively. The total effective rate in the combined therapy group was higher than those of the shallow-needle therapy group and the medication group separately (P<0.05). CONCLUSION: Shallow-needle therapy combined with estazolam is effective on insomnia of liver stagnation transforming into fire pattern, and its underlying effect mechanism is related to the reduction of plasma ACTH and CORT levels.

[Sleep-improving mechanism of Chaiqin Ningshen Granules in insomnia rats: based on hippocampal metabonomics].

With the ultra high performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-MS)-based metabonomics technology, this study aims to analyze the effect of Chaiqin Ningshen Granules(CNG) on endogenous metabolites in insomnia rats of liver depression syndrome and explore the sleep-improving mechanism of this prescription. Parachlorophenylalanine(PCPA, ip) and chronic stimulation were combined to induce insomnia of liver depression pattern in rats, and the effect of CNG on the macroscopic signs, hemorheology, and neurotransmitters in the hippocampus of insomnia rats of liver depression syndrome was observed. After the administration, rat hippocampus was collected for liquid chromatography-mass spectrometry(LC-MS) analysis of the metabolomics. Principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed for analyzing the metabolites in rat hippocampus and screening potential biomarkers. MetPA was used to yield the related metabolic pathways and metabolic networks. The results show that the drugs can significantly improve the mental state, liver depression, and blood stasis of rats, significantly increase the content of 5-hydroxytryptamine(5-HT) and gamma aminobutyric acid(GABA) in hippocampus(except low-dose CNG), and significantly reduce the content of glucose(Glu)(except low-dose CNG). Among them, estazolam and high-dose CNG had better effect than others. Metabolomics analysis yielded 27 potential biomarkers related to insomnia. MetPA analysis showed 4 metabolic pathways of estazolam in intervening insomnia and 3 metabolic pathways of high-dose CNG in intervening insomnia, involving purine metabolism, glycerophospholipid metabolism, histidine metabolism, and caffeine metabolism. CNG can alleviate insomnia by regulating endogenous differential metabolites and further related metabolic pathways. The result lays a basis for further elucidating the mechanism of CNG in improving sleep.

Acupuncture for cancer-related insomnia: A systematic review and meta-analysis.

BACKGROUND: Cancer-related insomnia is a highly prevalent complaint in cancer patients. However, there is no meta-analytic synthesis explored the efficacy of acupuncture for cancer-related insomnia among cancer patients undergoing active cancer treatments. OBJECTIVE: This systematic review and meta-analysis were performed to explore the efficacy and safety of acupuncture for insomnia in people diagnosed with cancer. STUDY DESIGN: Systematic review and meta-analysis of existing randomized controlled trials on acupuncture in the treatment of cancer-related insomnia. METHODS: According to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement, we identified and extracted the trials through November 2021 from ten databases and two trials record platforms (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PUBMED, Web of Science, PsycINFO, Allied and Complementary Medicine, Cumulative Index to Nursing and Allied Health Literature, China National Knowledge Infrastructure, Wanfang Digital Journals, ClinicalTrials, World Health Organization International Clinical Trials Registry Platform). The quality of the trials was assessed using Jadad score and Risk of Bias (2.0). A meta-analysis was synthesized using the random-effects model if the included studies were in high methodological quality. RESULTS: A total of 690 studies were identified, with 22 were included in the review, and 6 of them were included in the quantitative synthesis. Studies were highly heterogeneous in terms of participant characteristics and study methodologies. Most studies recruited patients diagnosed with a specific cancer type, and breast cancer patients were the subgroup most represented. The qualitative review of available evidence suggested a beneficial efficacy of acupuncture on sleep without serious adverse events in several studies (55%). The meta-analysis revealed that acupuncture produced a significant improvement in the total Pittsburgh Sleep Quality Index (PSQI) score relative to the wait-list control among breast cancer patients undergoing active cancer treatments (MD -1.92, 95% CI -3.25 to -0.59, p = 0.005). Similar improvement of real and sham acupuncture on PSQI score change post-intervention was found (MD: -0.68, 95% CI: -2.44 to 1.07, p = 0.44). Manual acupuncture had similar effective rate as compared to estazolam immediately post-intervention (RR: 0.94, 95% CI: 0.87 to 1.01, p = 0.09), and had significantly better effective rate than estazolam at 1-week post-intervention follow-up (RR: 1.25, 95% CI: 1.10 to 1.43, p = 0.0009). All reported acupuncture related adverse events were mild or moderate in severity. CONCLUSION: Acupuncture has great potential to be used to manage cancer-related insomnia for cancer patients or survivors. More studies with rigorous designs and larger sample size are warranted to verify the efficacy and safety of acupuncture for insomnia among people diagnosed with cancer, in particular among those with clinically significant insomnia. REGISTRATION: PROSPERO (ID: CRD42021285844).

Formation and occurrence of disinfection byproducts of benzodiazepine drug estazolam in drinking water of Beijing.

Estazolam (EZ) is a long-acting benzodiazepine (BZD) drug with high clinical consumption in China to treat anxiety, depression and other syndromes. Recently, it has been found as a leading potentially inappropriate medication among hospitalized elderly patients, increasing the risk of falls. It is discharged into the aquatic environment after use and has been frequently detected, ultimately affecting the safety of drinking water. In the present study, the reaction of EZ during chlorination disinfection was investigated in detail with regard to its transformation and kinetics. By means of ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS), four main disinfection byproducts (DBPs) were tentatively identified, and the transformation pathways were speculated to be cleavage at the imine linkage and oxidation on the diazepinone ring. The chlorination reaction rate in the pseudo-first-order kinetic model was significantly affected by free available chlorine (FAC) and pH. The increase in pH value led to a decrease in the reaction rate, while a higher dosage of chlorine resulted in a faster kinetic rate. We further estimated the potential toxicities of EZ and its DBPs using quantitative structure-activity relationship (QSAR) software tools. DBPs exhibited much higher toxicity than EZ and exhibited developmental toxicity and mutagenicity. Finally, a total of 108 drinking water samples were collected in the wet and dry seasons to determine actual residue changes in real environmental conditions. The detection frequency was 29% for EZ, and the highest concentration of 0.60 ng L-1 was found for its DBPs in tap water. No seasonal variations in concentration were observed. Overall, the results indicate that EZ and its DBPs may persist in drinking water, posing potential risks to public health.

Sleep-improving mechanism of Chaiqin Ningshen Granules in insomnia rats: based on hippocampal metabonomics / 中国中药杂志

With the ultra high performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-MS)-based metabonomics technology, this study aims to analyze the effect of Chaiqin Ningshen Granules(CNG) on endogenous metabolites in insomnia rats of liver depression syndrome and explore the sleep-improving mechanism of this prescription. Parachlorophenylalanine(PCPA, ip) and chronic stimulation were combined to induce insomnia of liver depression pattern in rats, and the effect of CNG on the macroscopic signs, hemorheology, and neurotransmitters in the hippocampus of insomnia rats of liver depression syndrome was observed. After the administration, rat hippocampus was collected for liquid chromatography-mass spectrometry(LC-MS) analysis of the metabolomics. Principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed for analyzing the metabolites in rat hippocampus and screening potential biomarkers. MetPA was used to yield the related metabolic pathways and metabolic networks. The results show that the drugs can significantly improve the mental state, liver depression, and blood stasis of rats, significantly increase the content of 5-hydroxytryptamine(5-HT) and gamma aminobutyric acid(GABA) in hippocampus(except low-dose CNG), and significantly reduce the content of glucose(Glu)(except low-dose CNG). Among them, estazolam and high-dose CNG had better effect than others. Metabolomics analysis yielded 27 potential biomarkers related to insomnia. MetPA analysis showed 4 metabolic pathways of estazolam in intervening insomnia and 3 metabolic pathways of high-dose CNG in intervening insomnia, involving purine metabolism, glycerophospholipid metabolism, histidine metabolism, and caffeine metabolism. CNG can alleviate insomnia by regulating endogenous differential metabolites and further related metabolic pathways. The result lays a basis for further elucidating the mechanism of CNG in improving sleep.

[Effect of Tongdu Tiaoshen acupuncture on serum GABA and CORT levels in patients with chronic insomnia].

OBJECTIVE: To observe the clinical effect of Tongdu Tiaoshen acupuncture on chronic insomnia, and explore its possible mechanism. METHODS: A total of 60 patients with chronic insomnia were randomly divided into an observation group (30 cases) and a control group (30 cases, 1 case dropped off ). The observation group was treated with Tongdu Tiaoshen acupuncture at Baihui (GV 20), Yintang (GV 29), Shenting (GV 24), etc. once every other day, 3 times a week. The control group was treated with estazolam tablets (1 mg) orally before going to bed every night. The treatments of both groups were required 4 weeks. The Pittsburgh sleep quality index (PSQI) scores, serum gamma-aminobutyric acid (GABA) and cortisol (CORT) levels were observed before and after treatment in the two groups, and the clinical effect was compared. RESULTS: After treatment, the sleep quality, day dysfunction scores of PSQI in the observation group and the falling asleep time, sleep time, sleep efficiency, sleep disturbance scores and total scores of PSQI in the two groups were lower than before treatment (P<0.01, P<0.05). After treatment, the daytime dysfunction score of PSQI in the observation group was lower than that in the control group (P<0.05). After treatment, the serum GABA levels in the two groups were higher than before treatment (P<0.05), and the serum CORT levels were lower than before treatment (P<0.01). The total effective rate was 90% (27/30) in the observation group and 93.1% (27/29) in the control group, the difference was not statistically significant (P>0.05). CONCLUSION: Tongdu Tiaoshen acupuncture has the same effect as western medication estazolam tablets in the treatment of patients with chronic insomnia, and has little effect on daytime dysfunction. The mechanism may be related to the increase of serum GABA level and the inhibition of the hyperactivation of hypothalamus-pituitary-adrenal (HPA) axis.

[Effect of acupuncture and estazolam on episodic memory and sleep structure in patients with chronic insomnia disorder: a randomized controlled trial].

OBJECTIVE: To compare the effect on chronic insomnia disorder (CID) and influences on episodic memory and sleep structure between acupuncture and estazolam tablets. METHODS: A total of 140 CID patients were randomized into a meridian-point group (46 cases, 1 case dropped off), a non-meridian-and-non-acupoint group (47 cases, 2 cases dropped off) and a medication group (47 cases, 2 cases dropped off). In the meridian-point group, Baihui (GV 20), Shenmen (HT 7), Sanyinjiao (SP 6), Zhaohai (KI 6) and Shenmai (BL 62) were selected and the routine acupuncture was applied. In the non-meridian-and-non-acupoint group, the needling technique was same as the meridian-point group. Acupuncture was given once daily for 4 weeks in the above two groups. In the medication group, estazolam tablets were administered orally, taken 1 to 2 mg per night, consecutively for 4 weeks. Before and after treatment, the changes in the following indexes were observed in each group, i.e. the score of insomnia severity index (ISI), the score of auditory verbal memory test (AVMT) and the relevant indexes of sleep structure [total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), sleep efficiency (SE) and the percentage of non rapid eye movement phase 1, 2 and 3 (N1, N2 and N3) and rapid eye movement time (REM) in TST]. RESULTS: After treatment, ISI scores were reduced in the meridian-point group and the medication group (P<0.01), the score in the meridian-point group was lower than the medication group and the non-meridian-and-non- acupoint group respectively (P<0.01) and that in the medication group was lower than the non-meridian-and-non-acupoint group (P<0.01). After treatment, the score of each of immediate recall, short-term delayed recall, long-term delayed recall and delayed recognition of AVMT was increased in the meridian-point group and the medication group respectively (P<0.01, P<0.05) and the score of each item of AVMT in the meridian-point group was higher than the medication group and the non-meridian-and-non-acupoint group respectively (P<0.01, P<0.05). The scores of immediate memory and delayed recognition in the medication group were higher than the non-meridian-and-non-acupoint group respectively (P<0.01). After treatment, SOL, WASO and N1% were all reduced (P<0.01) and TST, SE, N3% and REM% were all increased (P<0.01, P<0.05) in the meridian-point group and the medication group, N2% in the meridian-point group was reduced (P<0.01). After treatment, N1% and N2% in the meridian-point group were lower than the medication group (P<0.01) and N3% and REM% were higher than the medication group (P<0.01). After treatment, TST, SE and N3% in the meridian-point group and the medication group were all higher than the non-meridian-and-non-acupoint group respectively (P<0.01, P<0.05) and SOL, WASO and N1% were lower than the non-meridian-and-non-acupoint group respectively (P<0.01). REM% in the meridian-point group was also higher than the non-meridion-and-non-acupoint group (P<0.01), and N2% in the meridian-point group was also lower than the non-meridian-and-non-acupoint group (P<0.01). CONCLUSION: Compared with estazolam, acupuncture much better improves sleep quality and episodic memory in patients with chronic insomnia disorder, which is possibly related to the regulation of sleep structure of patients in treatment with acupuncture.

Detailed quantum mechanical studies on bioactive benzodiazepine derivatives and their adsorption over graphene sheets.

Estazolam (Z1) and related derivatives, adinazolam (Z2), alprazolam (Z3), 4-hydroxyalprazolam (Z4) and triazolam (Z5) have been studied by using various computational tools to analyze their geometry and spectral characteristics. The compounds were found to interact with graphene monolayer results shows that there is enhancement in various physico-chemical descriptors and surface enhanced Raman spectra (SERS). The various reactive descriptors obtained from the FMO analysis predict the reactive nature of the compound. The various lone pair/sigma to pi conjugation was analyzed using NBO formalism, which provides valuable information about intra molecular electron transfer which is vital in predicting the inherent stability of the molecule. Simulated electronic spectra using TD-DFT and CAM-B3LYP functional are discussed in detail with respect to electronic transitions and light harvesting efficiency. Suitability of candidates as a photo sensitizer in dye sensitized solar cells was studied and 4-Hydroxyalprazolam is identified as a suitable candidate. Nucleophilic and electrophilic regions of the molecules are identified using MESP, which adds to the reactivity information. It can be seen that the highest interaction energy has been obtained in the case of the Z5-graphene system, while the lowest interaction energy has been obtained in the case of the Z1-graphene system. Docking indicates that the ligands adsorbed over graphene also form stable complexes with the receptors as indicated by the high binding affinity energy values.

Pearl powder reduces sleep disturbance stress response through regulating proteomics in a rat model of sleep deprivation.

AIMS: This study aimed to explore whether pearl could help prevent cognitional morbidity and improve the metabolic processes of hippocampus. METHODS: Rats were divided into group of control (CTL), sleep deprivation (SD) and pearl powder (PP). The sleeplessness was introduced to all rats except control. Before and after administration with vehicle or pearl powder, cognition was evaluated by Morris water maze (MWM). The protein expression in hippocampus among all groups was examined using iTRAQ-based global proteomic analysis. RESULTS: Morris water maze tests revealed improvements of insomnia-induced cognitive deficit in both PP- and ES-treated rats, as compared to SD rats. However, proteomic analysis indicates that the pharmacological impact on gene expression of these two medicines is quite different: pearl is more capable of correcting aberrant gene expression caused by SD than estazolam. Therefore, pearl is more suitable for treatment of insomnia. These data, together with protein-protein interaction analysis, indicate that several pathways, affected by sleep deprivation, may be rescued by pearl powder: retrograde endocannabinoid signalling pathway, and the protein interaction or network enrich in oxidative phosphorylation Parkinson's disease and Huntington disease, etc CONCLUSIONS: Sleep deprivation can mimic cognition decline caused by insomnia with altered protein expression in the hippocampus; such behavioural and pathological changes can be significantly ameliorated by pearl powder.

A Rapid Detection Method for On-site Screening of Estazolam in Beverages with Au@Ag Core-shell Nanoparticles Paper-based SERS Substrate.

Estazolam (EST) is a common sedative-hypnotic drug with a risk of abuse. Therefore, rapid on-site detection of EST is necessary to control the abuse of EST. In this paper, a fast, simple, and sensitive method is demonstrated for the detection of EST in both water and beverages, using surface-enhanced Raman spectroscopy (SERS) techniques. Au@Ag core-shell nanoparticles (NPs) assembled on the filter paper as a SERS substrate exhibit good applicability and practicality. At the same time, density functional theory (DFT) is used to assign the vibration mode of the EST molecules, which can be used as a guide for subsequent experiments. The lowest detectable concentration of EST in aqueous solution can be as low as 5 mg/L, and signal uniformity is excellent (RSD687 = 5.56%, RSD1000 = 4.35%). In addition, EST components artificially added to orange juice and pomegranate juice can be effectively detected by simple pretreatment with a minimum detection concentration as low as 10 mg/L. Therefore, this study found that the use of Au@Ag core-shell nanoparticles paper-based SERS substrate provides a quick and easy method for the detection of illegally added drugs in beverages.

Effect of acupuncture and estazolam on episodic memory and sleep structure in patients with chronic insomnia disorder: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the effect on chronic insomnia disorder (CID) and influences on episodic memory and sleep structure between acupuncture and estazolam tablets.@*METHODS@#A total of 140 CID patients were randomized into a meridian-point group (46 cases, 1 case dropped off), a non-meridian-and-non-acupoint group (47 cases, 2 cases dropped off) and a medication group (47 cases, 2 cases dropped off). In the meridian-point group, Baihui (GV 20), Shenmen (HT 7), Sanyinjiao (SP 6), Zhaohai (KI 6) and Shenmai (BL 62) were selected and the routine acupuncture was applied. In the non-meridian-and-non-acupoint group, the needling technique was same as the meridian-point group. Acupuncture was given once daily for 4 weeks in the above two groups. In the medication group, estazolam tablets were administered orally, taken 1 to 2 mg per night, consecutively for 4 weeks. Before and after treatment, the changes in the following indexes were observed in each group, i.e. the score of insomnia severity index (ISI), the score of auditory verbal memory test (AVMT) and the relevant indexes of sleep structure [total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), sleep efficiency (SE) and the percentage of non rapid eye movement phase 1, 2 and 3 (N1, N2 and N3) and rapid eye movement time (REM) in TST].@*RESULTS@#After treatment, ISI scores were reduced in the meridian-point group and the medication group (<0.01), the score in the meridian-point group was lower than the medication group and the non-meridian-and-non- acupoint group respectively (<0.01) and that in the medication group was lower than the non-meridian-and-non-acupoint group (<0.01). After treatment, the score of each of immediate recall, short-term delayed recall, long-term delayed recall and delayed recognition of AVMT was increased in the meridian-point group and the medication group respectively (<0.01, <0.05) and the score of each item of AVMT in the meridian-point group was higher than the medication group and the non-meridian-and-non-acupoint group respectively (<0.01, <0.05). The scores of immediate memory and delayed recognition in the medication group were higher than the non-meridian-and-non-acupoint group respectively (<0.01). After treatment, SOL, WASO and N1% were all reduced (<0.01) and TST, SE, N3% and REM% were all increased (<0.01, <0.05) in the meridian-point group and the medication group, N2% in the meridian-point group was reduced (<0.01). After treatment, N1% and N2% in the meridian-point group were lower than the medication group (<0.01) and N3% and REM% were higher than the medication group (<0.01). After treatment, TST, SE and N3% in the meridian-point group and the medication group were all higher than the non-meridian-and-non-acupoint group respectively (<0.01, <0.05) and SOL, WASO and N1% were lower than the non-meridian-and-non-acupoint group respectively (<0.01). REM% in the meridian-point group was also higher than the non-meridion-and-non-acupoint group (<0.01), and N2% in the meridian-point group was also lower than the non-meridian-and-non-acupoint group (<0.01).@*CONCLUSION@#Compared with estazolam, acupuncture much better improves sleep quality and episodic memory in patients with chronic insomnia disorder, which is possibly related to the regulation of sleep structure of patients in treatment with acupuncture.

[Yinyang Ruyin acupuncture on refractory insomnia: a randomized controlled trial].

OBJECTIVE: To compare the therapeutic effect of Yinyang Ruyin acupuncture, conventional acupuncture and oral estazolam tablet on refractory insomnia. METHODS: A total of 180 patients with refractory insomnia were randomized into a Yinyang Ruyin acupuncture group, a conventional acupuncture group and a medication group, 60 cases in each group. In the Yinyang Ruyin acupuncture group, Yinyang Ruyin acupuncture was applied at Baihui (GV 20), Waiguan (TE 5), Neiguan (PC 6), Weishu (BL 21), Zhongwan (CV 12) and Taixi (KI 3); in the conventional acupuncture group, conventional acupuncture was applied at Baihui (GV 20), Shenmen (HT 7), Sanyinjiao (SP 6), Zhaohai (KI 6), Shenmai (BL 62) and Anmian (Extra). Supplementary acupoints were added according to different patterns in the two acupuncture groups, and the treatment was given once a day, 7 times as one course and 4 courses were required. In the medication groups, estazolam was taken orally 1 h before sleep, 1 mg each time, once a day for 4 weeks. The Pittsburgh sleep quality index (PSQI) score was observed before and after treatment and the therapeutic effect was evaluated in the 3 groups. RESULTS: The total effective rates in the Yinyang Ruyin acupuncture group and the conventional acupuncture group were 90.0% (54/60) and 83.3% (50/60), which were superior to 30.0% (18/60) in the medication group (both P<0.05). Compared before treatment, the PSQI scores were significantly reduced in the two acupuncture groups (all P<0.05), the sleep efficiency and the total score of PSQI were reduced in the medication group (both P<0.05). After treatment, the changes of sleep latency, sleep efficiency, sleep disorder, daytime function and total score of PSQI in the Yinyang Ruyin acupuncture group were significantly larger than those in the conventional acupuncture group (all P<0.05). The changes of PSQI scores in the Yinyang Ruyin acupuncture group were significantly larger than the medication group (all P<0.05). The changes of sleep quality, sleep latency, sleep time, sleep disorder, daytime function and total score of PSQI in the conventional acupuncture group were significantly larger than the medication group (all P<0.05). CONCLUSION: The therapeutic effect of Yinyang Ruyin acupuncture on refractory insomnia is superior to estazolam and conventional acupuncture.

Clinical effectiveness of Tui Na for insomnia compared with estazolam: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this systematic review (SR) is to evaluate the effectiveness and safety of Tui Na therapy for insomnia. METHODS: Two authors separately searched PubMed, the Cochrane Library, EMBASE, SinoMed Database, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science Technology Journal Database, related SR and published protocols at the same time to find randomized controlled trials (RCTs), which compared Tui Na therapy with estazolam therapy for insomnia, from their inception to January1st 2019. Screening documents, data extraction, quality assessment of methodology and quality assessment of evidence were also conducted by two authors separately at the same time. We used Cochrane Risk of Bias tool to assess the methodological quality of included RCTs. The results of meta-analysis were made via RevMan software (5.3). The quality of evidence was assessed by on-line GRADEpro. The primary outcome: Pittsburgh Sleep Quality Index (PSQI) score, the secondary outcome: clinical effectiveness rate and the safety index: adverse events. The clinical effectiveness of these included RCTs all focused on the improvement of patients' satisfaction with sleep time and sleep quality. RESULTS: We included 22 RCTs(1,999 participants), meeting the inclusion and exclusion criteria. The assessment of methodological quality was not satisfied, in which "high risk", "unclear risk" and "low risk" all existed. The results of meta-analysis demonstrated that (1)for primary outcome, the PSQI score of Tui Na therapy was lower than that of estazolam therapy after treatment in subgroup1(Head)(MD-2.39,95%CI[-3.79,-0.98],I2 = 82%,n = 291,3 trials) and subgroup4(Abdomen)(MD-1.7,95%CI[-2.53,-0.87],I2 = 0%,n = 120,2 trials);while there was no significant difference between Tui Na therapy and estazolam therapy in subgroup2(Head and trunk)(MD-1.39,95%CI[-3.03,0.24],I2 = 90%,n = 200, 2 trials) and subgroup3(Head, trunk and extremities)(MD-0.51,95%CI[-1.53,0.5],I2 = 30%,n = 126,2 trials).(2) for secondary outcomes(the clinical effectiveness rate and safety index),the clinical effectiveness rate of Tui Na therapy was higher than that of estazolam therapy after treatment in subgroup1(Head)(RR1.21,95%CI[1.05,1.39],I2 = 26%,n = 239,3 trials), subgroup2(Head and trunk)(RR1.15,95%CI[1.08,1.23],I2 = 33%,n = 1024,10 trials) and subgroup4(Abdomen)(RR1.12,95%CI[1.01,1.23],I2 = 0%,n = 180,3 trials); while there was no significant difference between Tui Na therapy and estazolam therapy in subgroup3(Head, trunk and extremities)(RR1.03,95%CI[0.94,1.13],I2 = 28%,n = 346,4 trials).Safety index, 5 RCTs reported adverse events. Among them, only 1 RCT reported adverse event in Tui Na therapy, which was daytime drowsiness; all 5 RCTs reported adverse events in estazolam therapy, which were dry mouth, dizziness, daytime drowsiness etc. The evidence quality was generally low to very low. CONCLUSION: Tui Na therapy appeared to be superior to estazolam therapy in treating areas(head; abdomen), while there was no significant difference between Tui Na therapy and estazolam therapy in treating areas(head and trunk; head, trunk and extremities). No serious adverse event was reported in Tui Na therapy. However the methodological quality and evidence quality were not satisfied. Therefore we could not make a convincing conclusion on the effectiveness and safety of Tui Na therapy for insomnia. Practitioners should combine their experience, evidence of our review and patients' preferences to make a proper treatment. And more high quality RCTs and well-designed protocols of Tui Na therapy for insomnia are needed in the future.

[A Forensic Autopsy Case in which Sulpiride and Estazolam Were Detected in an Adipoceratous Cadaver by LC-MS/MS].

We had a forensic autopsy case in which drugs were detected in a cadaver that had been stored in a cold and wet condition for 5 years. The skin of the cadaver was hard, and the color was partly whitish or dark brown. Though the cadaver had transformed into adipocere in the wet and cold condition, QuEChERS extraction and LC-MS/MS revealed the presence of sulpiride and estazolam in the femoral muscle and bone marrow. The concentrations of sulpiride and estazolam in the femoral muscle were 10.6 ng/g and 39.9 ng/g, respectively. The result of a drug screening test led not only to the cause of death but also to the personal identification of the cadaver. The individual had a history of drug taking, which had been stored in his medical records at the hospital for a long time. The fact of taking sulpiride and estazolam at the same time was characteristic, and it was useful in identifying the cadaver in this case. The progress in analytical technology has made possible the detection of particle drugs from old or adipoceratous cadavers, but there have been no reports of particle drugs being detected in a cadaver that had been dead for 5 years and had transformed to adipocere, as in our present case. The analytical results by LC-MS/MS were certainly important for the diagnosis of the cause of death, and, moreover, they were useful for the purpose of personal identification.

acupuncture on refractory insomnia: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the therapeutic effect of acupuncture, conventional acupuncture and oral estazolam tablet on refractory insomnia.@*METHODS@#A total of 180 patients with refractory insomnia were randomized into a acupuncture group, a conventional acupuncture group and a medication group, 60 cases in each group. In the acupuncture group, acupuncture was applied at Baihui (GV 20), Waiguan (TE 5), Neiguan (PC 6), Weishu (BL 21), Zhongwan (CV 12) and Taixi (KI 3); in the conventional acupuncture group, conventional acupuncture was applied at Baihui (GV 20), Shenmen (HT 7), Sanyinjiao (SP 6), Zhaohai (KI 6), Shenmai (BL 62) and Anmian (Extra). Supplementary acupoints were added according to different patterns in the two acupuncture groups, and the treatment was given once a day, 7 times as one course and 4 courses were required. In the medication groups, estazolam was taken orally 1 h before sleep, 1 mg each time, once a day for 4 weeks. The Pittsburgh sleep quality index (PSQI) score was observed before and after treatment and the therapeutic effect was evaluated in the 3 groups.@*RESULTS@#The total effective rates in the acupuncture group and the conventional acupuncture group were 90.0% (54/60) and 83.3% (50/60), which were superior to 30.0% (18/60) in the medication group (both <0.05). Compared before treatment, the PSQI scores were significantly reduced in the two acupuncture groups (all <0.05), the sleep efficiency and the total score of PSQI were reduced in the medication group (both <0.05). After treatment, the changes of sleep latency, sleep efficiency, sleep disorder, daytime function and total score of PSQI in the acupuncture group were significantly larger than those in the conventional acupuncture group (all <0.05). The changes of PSQI scores in the acupuncture group were significantly larger than the medication group (all <0.05). The changes of sleep quality, sleep latency, sleep time, sleep disorder, daytime function and total score of PSQI in the conventional acupuncture group were significantly larger than the medication group (all <0.05).@*CONCLUSION@#The therapeutic effect of acupuncture on refractory insomnia is superior to estazolam and conventional acupuncture.

Impact of breast cancer on prospective memory functioning assessed by virtual reality and influence of sleep quality and hormonal therapy: PROSOM-K study.

BACKGROUND: Breast cancer (BC) is the most frequent cancer in women with more than 70% of BC patients being treated with hormonal therapy (HT). Among these patients, some report difficulties in remembering what they are supposed to do at the right moment, referring to prospective memory (PM). PM is essential for autonomy and medical adherence of patients, and requires an ecological assessment. Virtual reality, that recreates naturalistic environment, seems to be a promising method to evaluate PM. Several BC patients also report sleep disturbances. Given the role of sleep on memory consolidation, it is imperative to explore the influence of sleep quality on PM in BC patients treated with HT. The purpose of PROSOM-K study is to assess PM functioning using virtual reality and sleep quality in BC treated or not with HT. METHODS: PROSOM-K is a prospective study including post-menopausal BC patients ≤70 years old treated with radiotherapy (n = 25) or with radiotherapy and HT (n = 25), and healthy post-menopausal women (n = 25) matched for age and education. PM will be assessed using a virtual reality based task. Other cognitive functions and psychosocial factors will be assessed with validated questionnaires and neuropsychological tests. The study is divided in 3 sessions: a session of familiarisation with the virtual environment and the PM task: a day-time session during which participants learn intentions during the morning and recall them in the evening; and a night-time session during which participants learn intentions in the evening and recall them the following morning. Women will be monitored by wrist actigraphy; during the night-time session, objective sleep quality and quantity will be measured by polysomnography. DISCUSSION: This is a novel study aiming to assess PM using virtual reality, coupled with the evaluation of other cognitive functions. Polysomnographic study of sleep will provide further information about architectural sleep disturbances in BC. Association between sleep architecture parameters and PM mechanism in BC women treated with HT will be described in detail. We expect our results will provide knowledge for patients and clinicians and further help to improve patient care and cognitive therapy. TRIAL REGISTRATION: NCT03420105 , registered: January 10, 2018.