Association between sleep-related phenotypes and gut microbiota: a two-sample bidirectional Mendelian randomization study.

Background: An increasing body of evidence suggests a profound interrelation between the microbiome and sleep-related concerns. Nevertheless, current observational studies can merely establish their correlation, leaving causality unexplored. Study objectives: To ascertain whether specific gut microbiota are causally linked to seven sleep-related characteristics and propose potential strategies for insomnia prevention. Methods: The study employed an extensive dataset of gut microbiota genetic variations from the MiBioGen alliance, encompassing 18,340 individuals. Taxonomic classification was conducted, identifying 131 genera and 196 bacterial taxa for analysis. Sleep-related phenotype (SRP) data were sourced from the IEU OpenGWAS project, covering traits such as insomnia, chronotype, and snoring. Instrumental variables (IVs) were selected based on specific criteria, including locus-wide significance, linkage disequilibrium calculations, and allele frequency thresholds. Statistical methods were employed to explore causal relationships, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighted Mode. Sensitivity analyses, pleiotropy assessments, and Bonferroni corrections ensured result validity. Reverse causality analysis and adherence to STROBE-MR guidelines were conducted to bolster the study's rigor. Results: Bidirectional Mendelian randomization (MR) analysis reveals a causative interplay between selected gut microbiota and sleep-related phenotypes. Notably, outcomes from the rigorously Bonferroni-corrected examination illuminate profound correlations amid precise compositions of the intestinal microbiome and slumber-associated parameters. Elevated abundance within the taxonomic ranks of class Negativicutes and order Selenomonadales was markedly associated with heightened susceptibility to severe insomnia (OR = 1.03, 95% CI: 1.02-1.05, p = 0.0001). Conversely, the augmented representation of the phylum Lentisphaerae stands in concord with protracted sleep duration (OR = 1.02, 95% CI: 1.01-1.04, p = 0.0005). Furthermore, heightened exposure to the genus Senegalimassilia exhibits the potential to ameliorate the manifestation of snoring symptoms (OR = 0.98, 95% CI: 0.96-0.99, p = 0.0001). Conclusion: This study has unveiled the causal relationship between gut microbiota and SRPs, bestowing significant latent value upon future endeavors in both foundational research and clinical therapy.

Causal association of gastroesophageal reflux disease with obstructive sleep apnea and sleep-related phenotypes: a bidirectional two-sample Mendelian randomization study.

Background: The interactions and associations between obstructive sleep apnea (OSA), sleep-related phenotypes (SRPs), and gastroesophageal reflux disease (GERD) are complex, thus it is hard to explore the effect and direction of causalities. Study objectives: A bidirectional Mendelian randomization (MR) study was performed to explore causal associations of GERD with OSA and SRPs (including insomnia, morningness, sleep duration, ease of getting up, daytime napping, daytime dozing, and snoring). Methods: First, we gathered summary statistics from publicly available databases. Subsequently, we identified single-nucleotide polymorphisms without strong linkage (r2 ≤ 0.001) by referencing relevant genome-wide association studies that met genome-wide significance criteria. Our primary analysis relied on inverse variance weighted to estimate the causal relationship. To ensure the validity of our findings, we also conducted several sensitivity analyses. These included MR Pleiotropy RESidual Sum and Outlier to detect and correct for potential pleiotropic effects, MR-Egger to assess directional pleiotropy, and weighted median analysis to further evaluate heterogeneity and pleiotropy. For the initial MR analysis, when causality was indicated by the results, instrumental variables that were significantly linked to the aforementioned confounding factors were removed. We will re-analyze the data after excluding outcome-related single nucleotide polymorphisms to confirm that the results are still consistent with the previous results. Results: GERD was found to increase the risk of OSA (OR = 1.53, 95% CI = 1.37-1.70, p = 5.3 × 10-15), insomnia (OR = 1.14, 95% CI = 1.10-1.19, p = 1.3 × 10-10), snoring (OR = 1.09, 95% CI = 1.04-1.13, p = 6.3 × 10-5) and less sleep duration (OR = 0.94, 95% CI = 0.91-0.97, p = 3.7 × 10-4). According to the reverse-direction analysis, there is an elevated risk of GERD associated with OSA (OR = 1.07, 95% CI = 1.02-1.12, p = 0.005), insomnia (OR = 1.95, 95% CI = 1.60-2.37, p = 1.92 × 10-11) and snoring (OR = 1.74, 95% CI = 1.37-2.21, p = 4.4 × 10-6). Conclusion: Genetic susceptibility to GERD can elevate the likelihood of experiencing insomnia, snoring, and OSA, in addition to diminishing sleep duration. Conversely, a reverse MR analysis indicates that ameliorating any one of insomnia, snoring, or OSA can mitigate the risk of developing GERD.

Trans-Anethole Alleviates DSS-Induced Ulcerative Colitis by Remodeling the Intestinal Flora to Regulate Immunity and Bile Acid Metabolism.

Ulcerative colitis (UC) is the most common inflammatory bowel disease (IBD); it is incurable, and the treatment is expensive. Trans-anethole (TA), the main component of fennel, exhibits various biological activities. An increasing number of studies have demonstrated the efficacy of herbal active ingredients in the treatment of UC. This study aimed to investigate the effect and mechanism of TA in UC. In this study, we have experimented on mice with dextran sulfate sodium salt (DSS)-induced UC. The TA group was gavaged with 62.5 mg/kg TA by gavage once daily on days 8-14. To observe the effect of TA on the colon tissue, various investigations were performed, including western blot and immunohistochemistry for intestinal barrier protein expression, TUNEL staining for apoptosis, western blot, and ELISA for inflammation level, flow cytometry for Th17/Treg, LC-MS for blood bile acid content, GC-MS for blood fatty acid content, and 16s RNA for intestinal contents. TA alleviated weight loss in mice with UC; increased colon length; alleviated intestinal mucosal damage; upregulated claudin-1, occludin, and ZO-1 protein expression levels; reduced inflammatory factors in the colon and serum; and alleviated apoptosis. TA reduced fatty acid and bile acid levels by inhibiting colony abundance and reducing Th17/Treg cell differentiation in the colon. We found that TA alleviates DSS-induced UC by remodeling the intestinal flora to regulate immunity and bile acid metabolism.

The nucleus accumbens functional connectivity in patients with insomnia using resting-state fMRI.

Background: The aim of this study was to investigate the functional abnormalities between the nucleus accumbens (NAc) and the whole brain in individuals with Insomnia Disorder (ID) using resting-state functional magnetic resonance imaging (fMRI). Additionally, the study aimed to explore the underlying neural mechanisms of ID. Methods: We enrolled 18 participants with ID and 16 normal controls (NC). Resting-state functional connectivity (FC) between the NAc and the whole brain voxels was calculated and compared between the two groups to identify differential brain region. Receiver operating characteristic (ROC) curve analysis was employed to assess the ability of differential features to distinguish between groups. Furthermore, Pearson correlation analysis was performed to examine the relationship between neurocognitive scores and differential features. Results: The ID group exhibited significantly reduced FC values in several brain regions, including the right supplementary motor area, the bilateral middle frontal gyrus, the bilateral median cingulate and paracingulate gyri and the left precuneus. The area under the curve (AUC) of the classification model based on FC in these brain regions was 83.3%. Additionally, the abnormal functional changes observed in ID patients were positively correlated with the Fatigue Severity Scale (R = 0.650, p = 0.004). Conclusion: These findings suggest that the NAc may play a crucial role in the diagnosis of ID and could serve as a potential imaging biomarker, providing insights into the underlying neural mechanisms of the disorder.

Theoretical study on the degradation mechanism, kinetics and toxicity for aqueous ozonation reaction of furan derivatives.

The compounds including furan-2,5-dicarboxylic acid (FDCA), 2-methyl-3-furoic acid (MFA), and 2-furoic acid (FA), containing Furan ring are considered to be possessing high ozone reactivity, although in depth studies of their ozonation processes have not been carried out yet. Hence, mechanism, kinetics and toxicity by quantum chemical, and their structure activity relationship are being investigated in this study. Studies of reaction mechanisms revealed that during the ozonolysis of three furan derivatives containing C=C double bond, furan ring opening occurs. At temperature (298 K) and pressure of 1 atm, the degradations rates of 2.22 × 103 M-1 s-1 (FDCA), 5.81 × 106 M-1 s-1 (MFA) and 1.22 × 105 M-1 s-1 (FA) suggested that the reactivity order is: MFA > FA > FDCA. In the presence of water, oxygen and ozone, the Criegee intermediates (CIs) as the primary products of ozonation would produce lower molecule weight of aldehydes and carboxylic acids by undergoing degradation pathways. The aquatic toxicity reveals that three furan derivatives play green chemicals roles. Significantly, most of the degradation products are least harmful to organisms residing in the hydrosphere. The mutagenicity and developmental toxicity of FDCA is minimum as compared to FA and MFA, which shows the applicability of FDCA in a wider and broader field. Results of this study reveal its importance in the industrial sector and degradation experiments.

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.

[Effect of moxibustion of "Ganshu"(BL18) and "Shenshu" (BL23) on musculoskeletal interaction in osteoporosis rats].

OBJECTIVE: To observe the effect of moxibustion of "Ganshu" (BL18)and "Shenshu" (BL23) on bone mineral density (BMD), biomechanics, bone metabolism and musculoskeletal morphology of osteoporosis (OP) rats, so as to explore its mechanism underlying treatment of OP via bone-muscle interaction. METHODS: Thirty-two female SD rats were randomly divided into sham operation, OP model, moxibustion and medication (nilestriol) groups, with 8 rats in each group. For rats of the sham operation group, a small amount of fat around the ovaries was removed, and those of the other 3 groups received removal of bila-teral ovaries for establishing OP model. Moxibustion was applied to bilateral BL18 and BL23 for 30 min, once every other day, 3 times a week for 12 weeks. Rats of the medication group received gavage of nilestriol (1 mg/kg) once a week for 12 weeks.After the interventions, a dual-energy absorptiometry was used to determine the BMD and bone mineral content of the rats' right femur and the fourth lumbar vertebrae under anesthesia, and three-point bending test used to detect the biomechanical properties (including load, displacement, stiffness) of the right femur. The levels of serum type I collagen C-terminal peptide (CTX-I), acid-resis-tant tartrate phosphatase (TRACP) and estradiol (E2) were determined using enzyme-linked immunosorbent assay, and histopathological changes of the left femur and the quadriceps observed after hematoxylin-eosin (H.E.) staining. RESULTS: Compared with the sham operation group, the BMD and bone mineral contents of the right femur and the fourth lumbar vertebra, the load and stiffness of the right femur, and concentration of serum E2 were significantly decreased (P<0.01, P<0.05), and the displacement of the right femur, and concentrations of serum CTX-Ⅰ and TRACP notably increased in the model group (P<0.01). After the interventions, the decreased levels of BMD and bone mineral contents, the load and stiffness and concentration of serum E2, and the increased levels of the displacement, and concentrations of serum CTX-Ⅰ and TRACP were all reversed by both moxibustion (except the bone mineral content of the fourth lumbar vertebra) and medication (P<0.01,P<0.05). No signi-ficant differences were found between moxibustion and medication in up-regulating the levels of BMD and bone mineral contents, the load and stiffness (except serum E2) and down-regulating the levels of the displacement, and concentrations of serum CTX-Ⅰ and TRACP (P>0.05). H.E. staining revealed that rats in the sham operation group showed mild thinness of the bone cortex, uneven thickness of trabecular bone, with distortion, fracture and osteoporosis of the left femur, and different size of rhabdomyocytes in the right quadriceps femoris muscle, with obvious proliferation of interstitial fibrous tissue and inflammatory cell infiltration, which were relatively and clearly milder in both moxibustion and medication groups. CONCLUSION: Moxibustion of BL18 and BL23 can increase the BMD and bone mineral content, improve biomechanical performance, adjust bone metabolism, and mitigate bone and the attached muscle histopathological changes in OP rats, suggesting that modulating interaction between bones and muscles is probably one of the ideas in the treatment of OP.

Health Benefits, Food Applications, and Sustainability of Microalgae-Derived N-3 PUFA.

Today's consumers are increasingly aware of the beneficial effects of n-3 PUFA in preventing, delaying, and intervening various diseases, such as coronary artery disease, hypertension, diabetes, inflammatory and autoimmune disorders, neurodegenerative diseases, depression, and many other ailments. The role of n-3 PUFA on aging and cognitive function is also one of the hot topics in basic research, product development, and clinical applications. For decades, n-3 PUFA, especially EPA and DHA, have been supplied by fish oil and seafood. With the continuous increase of global population, awareness about the health benefits of n-3 PUFA, and socioeconomic improvement worldwide, the supply chain is facing increasing challenges of insufficient production. In this regard, microalgae have been well considered as promising sources of n-3 PUFA oil to mitigate the supply shortages. The use of microalgae to produce n-3 PUFA-rich oils has been explored for over two decades and some species have already been used commercially to produce n-3 PUFA, in particular EPA- and/or DHA-rich oils. In addition to n-3 PUFA, microalgae biomass contains many other high value biomolecules, which can be used in food, dietary supplement, pharmaceutical ingredient, and feedstock. The present review covers the health benefits of n-3 PUFA, EPA, and DHA, with particular attention given to the various approaches attempted in the nutritional interventions using EPA and DHA alone or combined with other nutrients and bioactive compounds towards improved health conditions in people with mild cognitive impairment and Alzheimer's disease. It also covers the applications of microalgae n-3 PUFA in food and dietary supplement sectors and the economic and environmental sustainability of using microalgae as a platform for n-3 PUFA-rich oil production.

Association of Acupuncture and Auricular Acupressure With the Improvement of Sleep Disturbances in Cancer Survivors: A Systematic Review and Meta-Analysis.

Background: Studies on the efficacy of acupuncture and auricular acupressure on sleep disturbances in cancer patients have been growing, but there is no specific and comprehensive systematic review and meta-analysis. This review aims to evaluate the efficacy and safety of acupuncture and auricular acupressure on sleep disturbances in cancer survivors based on existing randomized clinical trials (RCTs). Methods: Four English-language and four Chinese-language biomedical databases were searched for RCTs published from database inception to July 30, 2021. RCTs comparing acupuncture and auricular acupressure with sham control, drug therapy, behavior therapy, or usual care for managing cancer were included. The quality of RCTs was appraised with the Cochrane Collaboration risk of bias (ROB) tool. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated for the effect sizes. Results: Thirteen RCTs with 961 patients were included. The risk of performance bias or reporting bias for most of the included trials was high or unclear. Evidence was not found for short-term effects on sleep scales compared to sham control (MD, 1.98; 95% CI, 0.33-3.64; p = 0.02; I2 = 36%), wait list control (MD, 0.40; 95% CI, -0.87-1.68; p = 0.54; I2 = 49%), drug therapy (MD, 1.18; 95% CI, -3.09-5.46; p = 0.59; I2 = 98%). For long-term effect, two sham-controlled RCTs showed no significance of acupuncture on insomnia scale scores (MD, 1.71; 95% CI, -2.38-5.81; p = 0.41; I2 = 89%). Subgroup analyses suggested no evidence that auricular acupressure (MD, 3.14; 95% CI=1.52, 4.76; p = 0.0001; I2 = 0%) or acupuncture (MD, 0.54; 95% CI=-1.27, 2.34; p = 0.56; I2 = 0%) was associated with the reduction in insomnia scale scores. Conclusions: This systematic review and meta-analysis found no evidence about acupuncture or auricular acupressure in the improvement of sleep disturbances in cancer survivors in terms of short- or long-term effect. Adverse events were minor. The finding was inconsistent with previous research and suggested that more well-designed and large-scale randomized controlled trials are needed to identify the efficacy of acupuncture and auricular acupressure for sleep disturbances in cancer survivors. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, CRD42020171612.

Production, Processing, and Protection of Microalgal n-3 PUFA-Rich Oil.

Microalgae have been increasingly considered as a sustainable "biofactory" with huge potentials to fill up the current and future shortages of food and nutrition. They have become an economically and technologically viable solution to produce a great diversity of high-value bioactive compounds, including n-3 polyunsaturated fatty acids (PUFA). The n-3 PUFA, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), possess an array of biological activities and positively affect a number of diseases, including cardiovascular and neurodegenerative disorders. As such, the global market of n-3 PUFA has been increasing at a fast pace in the past two decades. Nowadays, the supply of n-3 PUFA is facing serious challenges as a result of global warming and maximal/over marine fisheries catches. Although increasing rapidly in recent years, aquaculture as an alternative source of n-3 PUFA appears insufficient to meet the fast increase in consumption and market demand. Therefore, the cultivation of microalgae stands out as a potential solution to meet the shortages of the n-3 PUFA market and provides unique fatty acids for the special groups of the population. This review focuses on the biosynthesis pathways and recombinant engineering approaches that can be used to enhance the production of n-3 PUFA, the impact of environmental conditions in heterotrophic cultivation on n-3 PUFA production, and the technologies that have been applied in the food industry to extract and purify oil in microalgae and protect n-3 PUFA from oxidation.

Theoretical study on the formation of Criegee intermediates from ozonolysis of pentenal: An example of trans-2-pentenal.

In this study, we investigated the reaction mechanism and kinetics of ozone with trans-2-pentenal using density functional theory (DFT) and conventional transition state theory (CTST). At 298 K and 1 atm, the gas-phase reaction mechanisms and kinetic parameters were calculated at the level of CCSD(T)/6-311+G(d,p)//M06-2X/6-311+G(d,p). Both CC and CO bond cycloaddition as well as hydrogen abstraction were found. The calculations indicated that the main reaction path is 1,3-dipole cycloaddition reactions of ozone with CC bond with the relatively lower syn-energy-barrier of 3.35 kcal mol-1 to form primary ozonide which decomposed to produce a carbonyl oxide called a Criegee intermediate (CI) and an aldehyde. The subsequent reactions of CIs were analysed in detail. It is found that the reaction pathways of the novelty CIs containing an aldehyde group are extremely similar with general CIs when they react with NO, NO2, SO2, H2O, CH2O and O2. The condensed Fukui function were calculated to identify the active site of the chosen molecules. At 298 K and 1 atm, the reaction rate coefficient was 9.13 × 10-18 cm3 molecule-1 s-1 with atmospheric lifetime of 1.3 days. The calculated rate constant is in general agreement with the available experimental data. The branching ratios indicated that syn-addition pathways are prior to anti-addition. The atmospheric ratios for CIs formation and the bimolecular reaction rate constants for the Criegee intermediates with the variety of partners were calculated. Our theoretical results are of importance in atmospheric chemistry of unsaturated aldehyde oxidation by ozone.

Preoperative electroacupuncture for postoperative nausea and vomiting in laparoscopic gynecological surgery: a randomized controlled trial.

OBJECTIVE: We aimed to evaluate the effectiveness and safety of preoperative electroacupuncture (EA) on the incidence of postoperative nausea and vomiting (PONV), and severity of postoperative pain, in gynecological patients undergoing laparoscopic surgery. The effects of EA administered at different preoperative time points were compared. METHODS: A total of 413 patients undergoing elective laparoscopic gynecological surgery were randomly allocated into 4 groups receiving EA the day before surgery (Group Pre, n = 103), 30 min before (Group 30, n = 104) or both (Group Comb, n = 103), or usual care alone (Group Usual, n = 103). All acupuncture groups had usual care. The incidence of PONV and pain at 24 h were primary outcomes. Secondary outcomes included the severity of postoperative nausea, vomiting and pain, requirement for antiemetic medication and quality of recovery (QoR)-15 scores after surgery. RESULTS: There were significant differences between the four groups in nausea and vomiting incidence (0-24 h), postoperative antiemetic use (0-48 h), and postoperative pain (0-6 h), with the EA groups recording the lowest levels. Regarding primary outcomes, incidence of nausea and vomiting at 6-24 h was 28/11/18/11% (p = 0.003) 23/5/8/9% (p < 0.001), respectively, for Groups Usual/Pre/30/Comb. Accordingly, EA reduced the incidence of nausea and vomiting at 6-24 h by 61/34/60% and 79/65/61% for Groups Pre/30/Comb, respectively. Regarding secondary outcomes, incidence of nausea and vomiting at 0-6 h was 20/9/11/7% (p = 0.013) and 17/7/9/6% (p = 0.021), respectively, for Groups Usual/Pre/30/Comb. Rescue antiemetics at 0-6 h were required by 18/4/11/4% (p = 0.001) in Groups Usual/Pre/30/Comb. The mean numerical rating scale (NRS) pain score (0-10) at 0-6 h was significantly different between groups (2.45/1.89/2.01/1.97 for Groups Usual/Pre/30/Comb, p = 0.024). There were no significant differences between the three EA-treated groups. CONCLUSION: In gynecological patients undergoing laparoscopic surgery and treated with multimodal antiemetic methods, one session of preoperative EA may be a safe adjunctive treatment for PONV prophylaxis. Optimal timing of EA requires further verification. TRIAL REGISTRATION NUMBER: ChiCTR-INR-16010035 (Chinese Clinical Trial Registry).

[Electroacupuncture on motor function in patients with primary osteoporosis: a randomized controlled trial].

OBJECTIVE: To observe the effect of electroacupuncture on motor function and muscle state in patients with primary osteoporosis (POP). METHODS: A total of 60 female patients with POP were randomized into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 1 case dropped off). On the basis of adjusting lifestyle, caltrate was given orally in the control group, 2 pills a day for 4 weeks. On the basis of the treatment in the control group, electroacupuncture was applied at Zusanli (ST 36), Yanglingquan (GB 34), Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23), etc. in the observation group, with disperse-dense wave of 2 Hz/10 Hz in frequency, once every other day, 3 times a week for 4 weeks. The time of timed up-and-go test (TUGT) and the value of 10 m maximal walking speed (10 m MWS) before and after treatment were compared in the two groups, and the Young's modulus values of bilateral multifidus muscles in prone position and sitting position before and after treatment were compared by real-time shear wave elastography (SWE) in the two groups. RESULTS: After treatment, the TUGT time was decreased compared before treatment in the observation group (P<0.01), and that in the observation group was shorter than the control group (P<0.01). After treatment, the value of 10 m MWS test was increased compared before treatment in the observation group (P<0.05). After treatment, the Young's modulus values of bilateral multifidus muscles in prone position and sitting position were increased compared before treatment in the observation group (P<0.01); except for the left side in sitting position, the Young's modulus values of multifidus muscles in the observation group were higher than those in the control group (P<0.01, P<0.05). CONCLUSION: On the basis of oral caltrate, electroacupuncture can improve the motor function and muscle state in patients with POP.

Acupuncture combined with traditional Chinese medicine e-aid cognitive behavioral therapy for insomnia (TCM-eCBT-I) for chronic insomnia: study protocol for a randomized controlled trial.

INTRODUCTION: The incidence of insomnia is getting higher and higher. Long-term insomnia seriously affects people's health. Drug use is usually accompanied with adverse events. Both acupuncture and cognitive behavioral therapy for insomnia (CBT-I) have been proven to be safe and effective non-pharmacological treatments for insomnia. As the insomniacs' bad sleep behavior and wrong cognition have not been effectively corrected, acupuncture has a quick effect, high patient compliance but unstable long-term efficacy, while CBT-I is complex, time-consuming, and expensive; additionally, patient compliance is low, and the number of trained therapists is limited, making it difficult to carry out. Therefore, this study aims to use the insomnia TCM system to construct a convenient and feasible traditional Chinese medicine e-aid cognitive behavioral therapy for insomnia (TCM-eCBT-I) for Chinese people, and combine the advantages of acupuncture and TCM-eCBT-I for maintaining long-term efficacy, and three treatments will be evaluated to provide clinicians with a more effective clinical protocol METHODS AND ANALYSIS: This study is a single-center, open-label, randomized controlled trial. Ninety subjects will be recruited and randomly assigned to three groups: the acupuncture group, the TCM-eCBT-I group, and the acupuncture combined with TCM-eCBT-I group, in a ratio of 1:1:1. We will evaluate the Pittsburgh Sleep Quality Index (PSQI) and Dysfunctional Beliefs and Attitudes About Sleep Scale (DBAS), Insomnia Severity Index (ISI), sleep diary, Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and Fatigue Scale-14 Scale (FS-14) scales. All adverse reactions will be assessed through the ADVERSE event table. All outcomes will be evaluated online at 0 weeks, 4 weeks, 8 weeks, 16 weeks, and 28weeks. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of the Affiliated Hospital of Nanjing University of Chinese Medicine (2020 NL-018-02). Informed consent will be obtained from all the subjects. The results will be shared with sleep researchers, public, and relevant academic institutions through high-impact peer-reviewed publications. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000032960. Registered on 17 May 2020.

Effectiveness of different acupuncture therapies for chronic cancer pain: A protocol for systematic review and Bayesian network meta-analysis.

BACKGROUND: Pain is a common and distressing symptom experienced by cancer patients. Previous research found acupuncture was associated with significant reductions in pain intensity and opioid use. Acupuncture therapies are various, and the difference in efficacy and safety has never been assessed. This paper aims to assess and rank the effectiveness of the different acupuncture methods and provide an acupuncture treatment guideline for relieving chronic pain in cancer survivors. METHODS: Four English databases (PubMed, Embase, Cochrane library, and Web of Science) and 4 Chinese databases (China National Knowledge Infrastructure, Wanfang Data, and Chinese Biomedical Literature Database) will be searched for randomized controlled trials (RCTs) published from the database inception to November 30, 2021. The primary outcomes will be patient-reported pain intensity measured by the Brief Pain Inventory, Visual Analog Scale, Verbal Rating Scale, Numerical Rating Scale, and other valid outcome measures. The Grading of Recommendations Assessment, and Development and Evaluation System will evaluate the quality of evidence. Bayesian network meta-analysis will be performed in WinBUGS V.1.4.3 to determine the comparative effectiveness of the acupuncture therapies. RESULTS: This study will quantify the effectiveness of each acupuncture intervention for chronic cancer pain with pain scores and the use of analgesics. The adverse events of acupuncture treatment for cancer pain will also be reported. CONCLUSION: The conclusion of our study will help physicians and patients choose suitable acupuncture methods to manage cancer pain.

CTCF: A novel fusion partner of ETO2 in a multiple relapsed acute myeloid leukemia patient.

ETO2 is a nuclear co-repressor, which plays a critical role in the regulation of the cell cycle, self-renewal capacity, and differentiation of hematopoietic progenitor cells. We identified novel fusion transcripts involving ETO2 and CTCF by RNA-seq in a multiple relapsed AML case. The CTCF-ETO2 and ETO2-CTCF chimeric genes were validated by RT-PCR and Sanger sequencing. In addition, both transcripts apparently promoted cell proliferation via JAK/STAT3 pathway that is sensitive to STAT3 inhibitors. The novel fusions may have prognostic value and pathogenic mechanisms in acute myeloid leukemia.

New theoretical investigation of mechanism, kinetics, and toxicity in the degradation of dimetridazole and ornidazole by hydroxyl radicals in aqueous phase.

Dimetridazole (DMZ) and ornidazole (ONZ) have been widely used to treat anaerobic and protozoal infections. The residues of DMZ/ONZ persist in the water environment. The mechanisms and kinetics of hydroxyl-initiated oxidation, the primary DMZ/ONZ degradation method, were evaluated by quantum chemical methods.·OH-induced degradation of DMZ and ONZ shared many mechanistic and kinetic characteristics. The most feasible degradation pathway involved forming OH-imidazole adducts and NO2. The OH-imidazole adducts were subsequently degraded into double·OH imidazole intermediates. The rate coefficients for·OH degradation of DMZ and ONZ were 4.32 × 109 M-1 s-1 and 4.42 × 109 M-1 s-1 at 298 K, respectively. The lifetimes of DMZ and ONZ treated with·OH at concentrations of 10-9-10-18 mol L-1 at 298 K were τDMZ = 0.231-2.31 × 108 s and τONZ = 0.226-2.26 × 108 s, respectively. Toxicity assessment showed that the first degradation products of DMZ and ONZ exhibited enhanced aquatic toxicity, whereas most of the secondary degradation products were not harmful to aquatic organisms. Some of transformation products were still developmental toxicant or mutagenicity positive.

The Therapeutic Effect of Tacrolimus in a Mouse Psoriatic Model is Associated with the Induction of Myeloid-derived Suppressor Cells.

Objectives: Topical administration of Tacrolimus (TAC) is efective in the treatment of psoriasis in human patients and in mouse models. Previously, we showed that, though promoting the proliferative expansion of CD4+Foxp3+ regulatory T cells (Tregs), TNFR2 was protective in mouse psoriasis model. We thus examined the role of TNFR2 signal in the efect of TAC in the treatment of mouse psoriasis. Methods: To this end, psoriasis was induced in WT, or TNFR1 KO, or TNFR2 KO mice, and the psoriatic mice were treated with or without IMQ. Results: The results showed that TAC treatment potently inhibited the development of psoriasis in WT and TNFR1 KO mice, but not in TNFR2 KO mice. However, the treatment of TAC failed to induce the expansion of Tregs in psoriatic mice. In addition to playing a decisive role in the activation of Tregs, TNFR2 stimulates the generation and activation of myeloid-derived suppressor cells (MDSCs). This led us to found that the topical treatment with TAC markedly increased the number of MDSCs in the spleen of WT and TNFR1 KO mice, but not in TNFR2 KO mice. Consequently, TAC potently decreased serum levels of IL-17A, INF-γ, and TNF and their mRNA levels in the inflamed skin lesion. Conclusion: Therefore, our study for the first time found that the therapeutic efect of TAC in psoriasis is associated with the expansion of MDSCs in a TNFR2-dependent manner.

Acupuncture for hypertension with insomnia: Study protocol for a randomized, sham-controlled, subject-and-assessor-blinded trial.

Background: Previous studies show that insomnia and hypertension are closely related. Currently, intervention for hypertension with insomnia has become a research hotspot. Acupuncture, as a representative non-pharmaceutical therapy of traditional Chinese medicine (TCM), has been widely used in improving insomnia and hypertension. However, there are few clinical studies on acupuncture for hypertension with insomnia. Methods: A single-center, subject-and-assessor-blind, randomized, sham-controlled trial has been designed for a study to be conducted in Jiangsu Province Hospital of Chinese Medicine. Sixty eligible patients will be randomly assigned to the treatment group and the control group in a 1:1 ratio. The treatment group will receive acupuncture treatment, while the control group will receive sham acupuncture treatment. Both groups will be treated three times per week for 4 weeks. Data will be collected at baseline and after 4 weeks of treatment and analyzed by using SPSS 25.0. The primary outcome measures are sleep parameters of portable polysomnography before and after treatment. Secondary outcomes are Pittsburgh Sleep Quality Index, Insomnia Severity Index, home blood pressure, and heart rate variability. Discussion: This study aims to evaluate the efficacy of acupuncture using the portable polysomnography combined with sleep scales, and analyze heart rate variability to preliminarily explore the underlying mechanism of acupuncture on hypertension with insomnia. The trail, if proven to be effective, will provide strong scientific evidence to support acupuncture is effective to manage patients for hypertension with insomnia. Clinical trial registration: ChiCTR2200059161.

The top 100 most cited papers in insomnia: A bibliometric analysis.

Objective: The number of citations to a paper represents the weight of that work in a particular area of interest. Several highly cited papers are listed in the bibliometric analysis. This study aimed to identify and analyze the 100 most cited papers in insomnia research that might appeal to researchers and clinicians. Methods: We reviewed the Web of Science (WOS) Core Collection database to identify articles from 1985 to 24 March 2022. The R bibliometric package was used to further analyze citation counts, authors, year of publication, source journal, geographical origin, subject, article type, and level of evidence. Word co-occurrence in 100 articles was visualized using VOS viewer software. Results: A total of 44,654 manuscripts were searched on the Web of Science. Between 2001 and 2021, the top 100 influential manuscripts were published, with a total citation frequency of 38,463. The top countries and institutions contributing to the field were the U.S. and Duke University. Morin C.M. was the most productive author, ranking first in citations. Sleep had the highest number of manuscripts published in the top 100 (n = 31), followed by Sleep Medicine Reviews (n = 9). The most cited manuscript (Bastien et al., Sleep Medicine, 2001; 3,384 citations) reported clinical validation of the Insomnia Severity Index (ISI) as a brief screening indicator for insomnia and as an outcome indicator for treatment studies. Co-occurrence analyses suggest that psychiatric disorders combined with insomnia and cognitive behavioral therapy remain future research trends. Conclusion: This study provides a detailed list of the most cited articles on insomnia. The analysis provides researchers and clinicians with a detailed overview of the most cited papers on insomnia over the past two decades. Notably, COVID-19, anxiety, depression, CBT, and sleep microstructure are potential areas of focus for future research.