Tubuloside B, a major constituent of Cistanche deserticola, inhibits migration of hepatocellular carcinoma by inhibiting Hippo-YAP pathway.

BACKGROUND: Studies have shown that phenylethanoid glycosides (PhGs) have multiple pharmacological effects such as anti-inflammatory, hepatoprotective or neuroprotective functions, whereas their anti-tumor effects are rarely studied. Tubuloside B (Tub B) is a PhG isolated from Cistanche deserticola, a traditional Chinese medicine. To date, there is a lack of comprehensive research regarding the biological activity of Tub B. PURPOSE: The subject of the current study was to investigate the anti-hepatocellular carcinoma (HCC) cell activity and the underlying mechanism of Tub B. METHODS: We evaluated the in vitro anti-migratory effect of Tub B by scratch and transwell assays. RNA-seq was employed to identify the differential genes by Tub B. Besides, the functional mechanism of Tub B was investigated by distinct molecular biology techniques including immunofluorescent staining, quantitative PCR, as well as western blot analysis. Subsequently, we utilized Hep3B cells for in vivo metastasis assays through spleen injection and evaluated the anti-migratory effect of Tub B in hepatocellular carcinoma (HCC). RESULTS: Tub B exhibited in vitro and in vivo inhibition of HCC cell migration. Tub B decreased the expression of transcriptional target genes downstream of the Hippo pathway, including CTGF, CYR61, and N-cadherin as determined by RNA-seq. Furthermore, mechanistic studies confirmed that Tub B increased phosphorylation of YAP at S127, which contributes to YAP cytoplasmic localization. Additionally, overexpression of YAP abrogated Tub B-induced inhibition of HCC migration and the mRNA levels of CTGF, CYR61, and N-cadherin. CONCLUSIONS: Taken together, these results illustrated that Tub B demonstrated great potential in inhibiting migration of HCC, and a portion of its impact can be attributed to the modulation of the Hippo-YAP pathway.

A Machine Learning-Based Preclinical Osteoporosis Screening Tool (POST): Model Development and Validation Study.

Background: Identifying persons with a high risk of developing osteoporosis and preventing the occurrence of the first fracture is a health care priority. Most existing osteoporosis screening tools have high sensitivity but relatively low specificity. Objective: We aimed to develop an easily accessible and high-performance preclinical risk screening tool for osteoporosis using a machine learning-based method among the Hong Kong Chinese population. Methods: Participants aged 45 years or older were enrolled from 6 clinics in the 3 major districts of Hong Kong. The potential risk factors for osteoporosis were collected through a validated, self-administered questionnaire and then filtered using a machine learning-based method. Bone mineral density was measured with dual-energy x-ray absorptiometry at the clinics; osteoporosis was defined as a t score of -2.5 or lower. We constructed machine learning models, including gradient boosting machines, support vector machines, and naive Bayes, as well as the commonly used logistic regression models, for the prediction of osteoporosis. The best-performing model was chosen as the final tool, named the Preclinical Osteoporosis Screening Tool (POST). Model performance was evaluated by the area under the receiver operating characteristic curve (AUC) and other metrics. Results: Among the 800 participants enrolled in this study, the prevalence of osteoporosis was 10.6% (n=85). The machine learning-based Boruta algorithm identified 15 significantly important predictors from the 113 potential risk factors. Seven variables were further selected based on their accessibility and convenience for daily self-assessment and health care practice, including age, gender, education level, decreased body height, BMI, number of teeth lost, and the intake of vitamin D supplements, to construct the POST. The AUC of the POST was 0.86 and the sensitivity, specificity, and accuracy were all 0.83. The positive predictive value, negative predictive value, and F1-score were 0.41, 0.98, and 0.56, respectively. Conclusions: The machine learning-based POST was conveniently accessible and exhibited accurate discriminative capabilities for the prediction of osteoporosis; it might be useful to guide population-based preclinical screening of osteoporosis and clinical decision-making.

Clinical Efficacy of Diet Intervention Combined with Bismuth Potassium Citrate in Helicobacter pylori-Related Chronic Atrophic Gastritis.

Objective: To investigate the clinical impact of dietary intervention in combination with bismuth potassium citrate in the management of chronic atrophic gastritis (CAG) caused by Helicobacter pylori. Methods: From April 2019 to October 2022, 160 patients with newly identified Helicobacter pylori-related CAG were treated at our facility. They were split into two groups at random: the bismuth potassium citrate medication group (n = 80) and the diet intervention + bismuth potassium citrate experimental groups (n = 80). The bismuth potassium citrate treatment group was given bismuth potassium citrate capsule treatment only, and the diet intervention + bismuth potassium citrate treatment group was given diet intervention based on bismuth potassium citrate capsule. The diet intervention score, symptom score, and pathological score of the two groups were observed at baseline and after treatment, and the relationship between dietary intervention and symptoms and pathology of Helicobacter pylori-related CAG was analyzed. Results: During the baseline period, there was no discernible difference in the diet intervention score, symptom score, or pathology score between the two groups (P > .05); after the diet intervention combination treatment, the diet intervention score, diet intervention + bismuth potassium citrate experimental groups symptom score, and pathology score were considerably lower than those in the bismuth potassium citrate treated group (P < .05). Conclusions: Dietary intervention combined with bismuth potassium citrate exhibited more effective treatment than bismuth potassium citrate-only treatment in Helicobacter pylori-related CAG, which hinted us proper diet has a positive impact on improving the therapeutic efficacy of bismuth potassium citrate.

Tai Chi for the prophylaxis of episodic migraine: protocol of a non-inferiority randomized controlled trial with mechanism exploration.

BACKGROUND: Migraine is a complex neurovascular disorder with considerable clinical, social and economic issues. Tai chi has the potential to be an alternative prophylactic treatment for migraine with high safety since the adverse effects and limited efficacy of available medications. AIMS: The proposed study aims to compare the prophylaxis efficacy of 24-week Tai Chi training on migraine attacks with the standard prophylactic medication; and to explore the mechanism of Tai Chi in preventing migraine attacks by analyzing the associations between changes of migraine attacks and changes of neurovascular functions and inflammatory makers. METHOD: This is a two-arm parallel non-inferiority randomized controlled trial. In total 220 Hong Kong Chinese women aged 18-65 years with diagnosis of episodic migraine will be recruited and randomized to either the Tai Chi training group or the standard prophylactic medication group with 1:1 ratio, and receive the 24 weeks of modified 33-short form Yang-style Tai Chi training and the standard prophylactic medications, respectively. A 24-week follow-up will be implemented for both groups. For efficacy examination, the primary outcome was the frequency of migraine attacks measured by the migraine diary; and for the mechanism exploration, the primary outcome was the volume and number of white matter hyperintensity (WMH) measured by magnetic resonance imaging (MRI). The measurements will be conducted at the baseline, 24th weeks, and 48th weeks. Linear mixed model will be adopted to comprehensively analyze the changes of variables within and between groups. DISCUSSION: Given the importance of reducing disease burden and financial cost of migraine attacks, the findings of this study will provide new insights regarding the role of Tai Chi in alleviating migraine burden and further shed light on the mechanism action of Tai Chi on preventing headache attacks. TRIAL REGISTRATION: ClinicalTrials.gov NCT05690737. Registered on January 28, 2023.

Efficacy and feasibility of a 12-week Tai Chi training for the prophylaxis of episodic migraine in Hong Kong Chinese women: A randomized controlled trial.

Background: Tai Chi has been broadly applied as alternative treatment for many neurological and psychological disorders. Whereas no study using Tai Chi as prophylactic treatment for migraine. The purpose of this study was to preliminarily examine the efficacy and feasibility of a 12-week Tai Chi training on migraine attack prevention in a sample of Chinese women. Methods: A two-arm randomized controlled trial was designed. Women aged 18 to 65 years and diagnosed with episodic migraine were randomized to either Tai Chi group (TC group) or the waiting list control group. A modified 33-short form Yang-style Tai Chi training with 1 h per day, 5 days per week for 12 weeks was implemented in the TC group, with a 12-week follow up period. The control group received a "delayed" Tai Chi training at the end of the trial. The primary outcome was the differences in attack frequency between 4 weeks before baseline and at the 9-12 weeks after randomization. The intensity and duration of headache were also measured. The feasibility was evaluated by the maintenance of Tai Chi practice and satisfactory level of the participants toward training. Results: Eighty-two women were randomized, finally 40 in TC group and 33 in control group were involved in the analysis. On average, women in TC group had 3.0 times (95% CI: -4.0 to -2.0, P < 0.01) and 3.6 days (95% CI: -4.7 to -2.5, P < 0.01) reduction of migraine attack per month. Compared with the control group, the differences were statistically significant (-3.7 attacks/month, 95% CI: -5.4 to -1.9; and -3.0 migraine days/month, 95% CI: -4.5 to -1.5; both P < 0.001). The intensity and duration of headache had 0.6 (95% CI: -1.2 to -0.0, P < 0.05) units and 1.2 (IQR: -5.0 to 1.1, P < 0.05) hours reduction in TC group, respectively. Most of the participants (69.2%-97.4%) were satisfied with the training. At the end of 24 weeks, on average, the participants maintained 1.5 times of practice per week and 20 min for each practice. Conclusion: The 12-week Tai Chi training significantly decreased the frequency of migraine attack. It was acceptable and practicable among female migraineurs. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT03015753.

Effectiveness of Tai Chi on Blood Pressure, Stress, Fatigue, and Sleep Quality among Chinese Women with Episodic Migraine: A Randomised Controlled Trial.

The beneficial effects of Tai Chi on the cardiovascular risk profile and the migraine trigger factors among female migraineurs remain unknown. This study aimed to evaluate the effectiveness of a 12-week Tai Chi training on blood pressure (BP) and migraine-related trigger factors, including stress, fatigue, and sleep quality among Chinese women with episodic migraine. In this study, eligible Hong Kong Chinese women aged 18-65 years were randomly assigned to the Tai Chi group adopting a modified 33-short form of Yang style Tai Chi training for 12 weeks, followed by additional 12 weeks of self-practice or the waiting list control group that maintained the usual lifestyle for 24 weeks. The primary outcome was the changes in BP from the baseline to 12 and 24 weeks. The secondary outcomes included the stress level, fatigue, and sleep quality measured by the perceived stress scale (PSS), the numeric rating scale-fatigue (NRS-fatigue), and the Pittsburgh sleep quality index (PSQI), respectively. Significant between-group differences were found in systolic BP (-6.8 mmHg at 24 weeks, P=0.02), and a decreasing trend was significant across baseline, 12 weeks, and 24 weeks between groups (P < 0.05). The 12-week Tai Chi training significantly reduced the BP level and moderately improved stress level, fatigue status, and sleep quality among Chinese women with episodic migraine. Therefore, Tai Chi could be considered a promising mind-body exercise with good feasibility for migraineurs in the future. This trial is registered with registration number NCT03015753.

Tubuloside B, isolated from Cistanche tubulosa, a promising agent against M1 macrophage activation via synergistically targeting Mob1 and ERK1/2.

Targeting macrophage M1 polarization is a promising strategy with fewer detrimental effects in COVID-19 curation. Phenylethanoid glycosides (PhGs) of Cistanche tubulosa are a botanical drug to possess various anti-inflammation-related functions, such as immunomodulating, hepatoprotective or neuroprotective functions, whereas their anti-inflammatory activity is rarely understood. A search into their anti-inflammatory characteristics led to the isolation of 49 PhGs along with 15 new PhGs. Their inhibitory effects against M1 polarization induced by LPS plus IFN-γ were explored in RAW264.7 macrophages. Of these PhGs, tubuloside B (Tub B) exerted substantial NO scavenging effect both in chemical- and cell-based assays, and it inhibited massive production of cytokines and chemokines. Tub B decreased ERK1/2 phosphorylation via direct binding and inhibited the MAPK signaling pathway. Tub B also directly binded to Mob1 protein, thereby increased the stability and level of Mob1 protein by inhibiting ubiquitinated degradation. Mob1 was pivotal for the anti-inflammatory activity of Tub B, and it acted independently of the canonical Hippo-YAP pathway. Moreover, ERK1/2 and Mob1 also had a synergic effect on modulating the inflammatory response. Finally, these effects of Tub B were verified in mice with LPS-induced systemic inflammatory response syndrome. Taken together, these results indicated that Tub B acted as a promising agent against M1 macrophage activation by synergistically targeting ERK1/2 and Mob1, and that it may potentially be a drug candidate to prevent/treat inflammatory diseases, especially in COVID-19.

The Role of Alternative Splicing in Cancer: Regulatory Mechanism, Therapeutic Strategy, and Bioinformatics Application.

[Formula: see text] Alternative splicing (AS) can generate distinct transcripts and subsequent isoforms that play differential functions from the same pre-mRNA. Recently, increasing numbers of studies have emerged, unmasking the association between AS and cancer. In this review, we arranged AS events that are closely related to cancer progression and presented promising treatments based on AS for cancer therapy. Obtaining proliferative capacity, acquiring invasive properties, gaining angiogenic features, shifting metabolic ability, and getting immune escape inclination are all splicing events involved in biological processes. Spliceosome-targeted and antisense oligonucleotide technologies are two novel strategies that are hopeful in tumor therapy. In addition, bioinformatics applications based on AS were summarized for better prediction and elucidation of regulatory routines mingled in. Together, we aimed to provide a better understanding of complicated AS events associated with cancer biology and reveal AS a promising target of cancer treatment in the future.

Phlorizin alleviates cholinergic memory impairment and regulates gut microbiota in d-galactose induced mice.

We explored the effect of phlorizin against cholinergic memory impairment and dysbacteriosis in D-galactose induced ICR mice. The control (CON) group, D-galactose model (DGM) group, and three groups (DG-PL, DG-PM, DG-PH) treated with phlorizin at 0.01%, 0.02%, and 0.04% (w/w) in diets were raised for 12 weeks. Supplementing with phlorizin reversed the loss of organ coefficient and body weight caused by D-galactose. The functional abilities of phlorizin on hippocampal-dependent spatial learning and memory, anti-oxidation, anti-inflammation were also observed. Meanwhile, phlorizin intervention upregulated the gene expression of Nrf2, GSH-PX, SOD1, decreased the gene expression of NF-κB, TLR-4, TNF-α, and IL-1ß in the hippocampus, while enhanced the gene expression of JAM-A, Mucin2, Occludin in the caecum. Furthermore, a neurotransmitter of acetylcholine (ACh) was enhanced, while acetylcholinesterase (AChE) activity was inhibited by phlorizin administration. Moreover, phlorizin administration increased short-chain fatty acids (SCFAs) content, and reduced lipopolysaccharides (LPS) levels, which may relate to the rebuilding of gut microbiota homeostasis. Treatment with phlorizin may be an effective intervention for alleviating cognitive decline and gut microbiota dysbiosis.

Acupuncture Reduced the Risk for Insomnia in Stroke Patients: A Propensity-Score Matched Cohort Study.

Background: Post-stroke insomnia (PSI) affects the quality of life for stroke patients, reduces the likelihood of successful rehabilitation, and produces additional complications following stroke. Previous reports have provided some information regarding PSI risk factors, but little is known concerning protective factors for PSI. This study analyzed the relationship between acupuncture and insomnia in stroke patients and explored the use of acupuncture as a preventive treatment. Methods: Patients diagnosed with stroke from 2010 to 2019 were identified in the case database of the First Affiliated Hospital of Guangzhou University of Chinese These patients followed until 2020, and numerous factors were examined, including gender, age, stroke type, stroke location, and baseline comorbidities. A 1:1 propensity score was used to match an equal number of patients receiving acupuncture with stroke patients who did not receive acupuncture (N = 1,680 for each group). The purpose of the study was to compare the incidence of insomnia in these two stroke cohorts. We used the Cox regression model and Kaplan-Meier method to estimate the risk of insomnia as the outcome event. Results: Compared with the non-acupuncture cohort in general, stroke patients who received acupuncture treatment exhibited a lower risk of insomnia after adjusting for age, gender, stroke type, stroke location, and comorbidities (adjusted hazard ratio HR = 0.27, 95% confidential interval = 0.23 to 0.32). Acupuncture also reduced the risk of PSI for both genders. The respective risks were HR = 0.28 (adjusted) for males and HR = 0.26 (adjusted) for females. Acupuncture also lowered the risk for PSI for different age groups. The risks were HR = 0.22 (adjusted) for individuals 18 to 39 years of age, HR = 0.31 (adjusted) for individuals 40 to 59 years of age, HR = 0.28 (adjusted) for those 60 to 79 years of age, and HR = 0.18 (adjusted) for individuals 80 years of age and older. Concerning the stroke type, regardless of whether the stroke was ischemic, hemorrhagic, or a combination of the two stroke types, patients who received acupuncture exhibited lower risk (adjusted HR = 0.28, 0.17, and 0.49, respectively). Concerning stroke location, except for the cerebral hemispheres (adjusted HR = 1.10, 95% confidential interval = 0.12 to 1.01), the risk of PSI after receiving acupuncture was lower for the frontal lobe (adjusted HR = 0.42), the basal ganglia (adjusted HR = 0.22), the radiation crown (adjusted HR = 0.42), the diencephalon (adjusted HR = 0.20), or multiple partial strokes (adjusted HR = 0.26), the risk of PSI after receiving acupuncture was lower. For all baseline complications, acupuncture reduced the risk of insomnia. The cumulative incidence of insomnia in the acupuncture cohort was significantly lower than the non-acupuncture cohort (log-rank test, P = 0.000). Limitations: First, our research only included patients from a single center. Second, we did not classify the post-stroke insomnia severity. Second, the information was extracted manually. Overall, the sample size was small, and we needed to increase the sample size to strengthen the conclusions. Conclusion: Acupuncture treatment reduced the risk of insomnia in stroke patients. Future research be conducted with increased sample sizes and further elaboration on the specific acupuncture protocols that were used.

Effects of Basketball and Baduanjin Exercise Interventions on Problematic Smartphone Use and Mental Health among College Students: A Randomized Controlled Trial.

Problematic smartphone use (PSU) has become a prevalent issue worldwide. Previous studies suggest that physical exercising may effectively reduce smartphone users' addiction levels. Comparisons and further evaluations on the long-term effects of different types of exercise-based interventions on treating PSU remain to be investigated. Objective. We investigated if group-based basketball and Baduanjin exercise (a type of Qigong) would reduce PSU and improve the mental health of college students and whether such effects would be sustained. A twelve-week experiment was conducted, where 96 eligible Chinese college students with PSU were randomly assigned to two intervention arms (i.e., basketball and Baduanjin exercises) and a control arm. Outcome measures, including PSU (measured by the Mobile Phone Addiction Index in Chinese (MPAI)) and mental health indices for anxiety (measured by Self-Rating Anxiety Scale (SRAS)), loneliness (measured by the short-form of the UCLA Loneliness Scale (UCLA-LS)), inadequacy (measured by the revised Janis and Field's Feelings of Inadequacy Scale (FIS)), and stress (measured by the Chinese version of Perceived Stress Scale (CPSS)) were collected at the baseline, the end of week 12, and the two-month follow-up. A Generalized Estimating Equations (GEE) model for longitudinal data was utilized in analyses. Results. Both exercise interventions demonstrated significant effects on decreasing PSU (basketball: p < 0.01; Baduanjin: p < 0.01), feelings of anxiety (basketball: p < 0.01; Baduanjin: p=0.04), loneliness (basketball: p < 0.01; Baduanjin: p < 0.01), inadequacy (basketball: p < 0.01; Baduanjin: p < 0.01), and perceived stress (basketball: p < 0.01; Baduanjin: p=0.04), at the end of interventions. At two months after interventions, both exercise interventions demonstrated significant effects on decreasing PSU (basketball: p < 0.05; Baduanjin: p < 0.05), feelings of anxiety (basketball: p < 0.01; Baduanjin: p=0.03), loneliness (basketball: p < 0.01; Baduanjin: p < 0.01), and inadequacy (basketball: p < 0.01; Baduanjin: p=0.01), but not for feeling of stress. Furthermore, group-based basketball demonstrated larger improvements for all these significant results on reducing PSU and meanwhile improving their related mental health parameters among college students.

Correlation Between Cognition and Balance Among Middle-Aged and Older Adults Observed Through a Tai Chi Intervention Program.

BACKGROUND: Age-associated decline in cognition and balance may cause severe ability loss for daily living activities among middle-aged and older adults. The relationship between cognition and balance in this aging population remains to be explored. OBJECTIVE: The present study Is exploratory in nature and aimed to examine the relationship between balance (both static and dynamic components) and global cognitive function among middle-aged and older adults through Tai Chi (TC) practice as a research avenue. METHODS: A short-term (12 weeks) intervention of TC was conducted among middle-aged and older adults in the community setting. Global cognitive function (using the Chinese version of the Montreal Cognitive Assessment score (MoCA) and balance (i.e., one leg standing test score; Timed Up and Go Test score, TUGT) of all participants were assessed before and after the intervention. Age, body mass index (BMI), sex, and physical fitness variables (Chair Stand Test, CST; the 6-Meter Walk Test, 6MWT) were also collected as confounding factors. RESULTS: Significant moderator effects of baseline CST on the association between the dichotomized baseline MoCA score and the baseline left leg balance score (p = 0.0247), the baseline right leg balance score (p = 0.0140) and the baseline TUGT score (p = 0.0346) were found. Change score of left score balance (p = 0.0192) and change score of TUGT (p = 0.0162) were found to be significantly associated with change score of cognitive function. CONCLUSION: Cognitive function and balance are interrelated in middle-aged and older adults. The association between global cognitive function and balance Is moderated by strength of lower limbs. The change scores of cognitive function and balance introduced by TC training were found to be positively correlated. Future research Is warranted to further confirm the cause-effect relationship of cognitive function and balance and its influencing factors among middle-aged and older adults utilizing intervention studies with larger sample sizes.

Mental Imagery and Acute Exercise on Episodic Memory Function.

Mental imagery is used extensively in the sporting domain. It is used for performance-enhancement purposes, arousal regulation, affective and cognitive modification, and rehabilitation purposes. The purpose of this experiment was to evaluate whether acute exercise and mental imagery of acute exercise have similar effects on cognitive performance, specifically memory function. A within-subject randomized controlled experiment was employed. Participants (N = 24; Mage = 21.5 years) completed two exercise-related visits (i.e., actual exercise and mental imagery of exercise), in a counterbalanced order. The acute-exercise session involved 10 min of intermittent sprints. The mental-imagery session involved a time-matched period of mental imagery. After each manipulation (i.e., acute exercise or mental imagery of acute exercise), memory was evaluated from a paired-associative learning task and a comprehensive evaluation of memory, involving spatial-temporal integration (i.e., what, where, and when aspects of memory). Bayesian analyses were computed to evaluate the effects of actual exercise and mental imagery of exercise on memory function. For the paired-associative learning task, there was moderate evidence in favor of the null hypothesis for a main effect for condition (BF01 = 2.85) and time by condition interaction (BF01 = 3.30). Similarly, there was moderate evidence in favor of the null hypothesis for overall (what-where-when) memory integration (BF01 = 3.37), what-loop (BF01 = 2.34), where-loop (BF01 = 3.45), and when-loop (BF01 = 3.46). This experiment provides moderate evidence in support of the null hypothesis. That is, there was moderate evidence to support a non-differential effect of acute exercise and mental imagery of acute exercise on memory function.

Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals.

BACKGROUND: Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions. OBJECTIVES: This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population. METHODS: Summary results collected from 153,014 individuals (54.4% women; mean age 55.1 ± 12.1 years) from 33 studies (of 5 ancestries) were meta-analyzed. Linear regression analyses examining associations between electrolyte concentrations (mmol/l of calcium, potassium, sodium, and magnesium), and electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals) were performed. The study adjusted for potential confounders and also stratified by ancestry, sex, and use of antihypertensive drugs. RESULTS: Lower calcium was associated with longer QT intervals (-11.5 ms; 99.75% confidence interval [CI]: -13.7 to -9.3) and JT duration, with sex-specific effects. In contrast, higher magnesium was associated with longer QT intervals (7.2 ms; 99.75% CI: 1.3 to 13.1) and JT. Lower potassium was associated with longer QT intervals (-2.8 ms; 99.75% CI: -3.5 to -2.0), JT, QRS, and PR durations, but all potassium associations were driven by use of antihypertensive drugs. No physiologically relevant associations were observed for sodium or RR intervals. CONCLUSIONS: The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation by >5 ms.

Efficacy of different-frequency TEAS on acute pain after the total knee arthroplasty: a study protocol for a parallel group randomized trial.

BACKGROUND: Total knee arthroplasty (TKA) is an optimal option for patients with middle-to-end-stage knee osteoarthritis. However, the management of postoperative acute pain remains inefficient. Transcutaneous electrical acupoint stimulation (TEAS) is a nonpharmacological method to manage postoperative acute pain. Different frequencies of TEAS have been tested using varying parameters, but the optimal analgesic frequency remains controversial. The aim of this study was to explore the optimal analgesic frequency of TEAS for treating acute pain after the primary unilateral TKA. METHODS/DESIGN: This is a double-blind, randomized controlled trial. A total of 156 patients are randomly assigned to: G1, 5 Hz TEAS; G2, 100 Hz TEAS; G3, mixed TEAS (alternative use of daily 5 Hz and 100 Hz TEAS) and G4, placebo TEAS. In the G1, G2 and G3 groups, TEAS is conducted at acupoints SP9 and GB34 of the leg that was operated on (at a wave of continuous, balanced and asymmetrical biphasic square, with a pulse width of 200 µs, and a strong but comfortable current) for 30 min prior to a 30-min rehabilitation session per day for 2 weeks. In G4 group, TEAS is delivered at a strong but comfortable current for 30 s, then the current is gradually decreased to none over the next 15 s. The primary outcomes are measured before surgery, at baseline (POD 3, before TEAS intervention), week 1 and 2 after TEAS intervention with the Numeric Pain Rating Scale and The American Knee Society Score. The secondary outcomes include: (1) Active range of motion of the knee that was operated on; (2) Surface electromyography of both quadriceps; (3) Modified 30-s sit to stand test; (4) Additional usage of analgesia; and (5) SF-36. The additional outcomes include: (1) Patients' satisfaction rate; (2) Patient's expectation rate; and (3) Incidence of analgesia-related side effects. To test the blinding of participants and assessors, they are asked to guess whether the subjects received active or placebo TEAS within 5 min after the latest intervention. The safety and financial cost of TEAS are assessed. DISCUSSION: Mixed TEAS has more favorable effect on acute pain control than the placebo or 5 Hz or 100 Hz TEAS. TRIAL REGISTRATION: ChiCTR1800016347 . Date of registration was 26 May 2018. Retrospectively registered.

[Effects of carbon supplementary modes on phosphorus bioaccumulation/phosphorus harvesting process in a tidal flow constructed wetland.] / 碳源补å 方式对潮汐流人工湿地生物蓄磷/磷移除的影响.

We explored the effects of carbon supplementary modes on operational performance in a tidal flow constructed wetland (TFCW) utilizing phosphorus bioaccumulation/phosphorus harvesting (PB-PH) process. Three different carbon supplementary modes were adopted during the periodical phosphorus harvesting process. The results showed that the carbon supplementary mode significantly affected the performances of phosphorus bioaccumulation and phosphorus harvesting throughout the experiment. The optimization of carbon supplementary mode would facilitate the maintenance of abundance and activities of polyphosphate-accumulating organisms (PAOs). Subsequently, the amounts of phosphorus release and PHB synthesis in PAOs, as well as the utilization rate of supplementary carbon, could be effectively enhanced during the phosphorus harvesting process. The efficient and stable phosphorus removal effects of the TFCW could be ensured during the phosphorus bioaccumulation process. When the PB-PH cycle length was 30 d and using the continuous circulation carbon supplementary mode, the amount of phosphorus retained in the bed and the mean phosphorus harvesting efficiency of the TFCW were 26994.88 mg and 70.8%, respectively. Regarding a typical PB-PH cycle, the mean phosphorus removal efficiency of the TFCW could achieve (91.4±2.1)% during the phosphorus bioaccumulation process. The amounts of phosphorus release and PHB synthesis in PAOs, and the utilization rate of supplementary carbon in the system could reach up to (1563.72±127.84) mg, (4.52±0.39) mmol C·g-1 VSS, and (97.3±1.6)%, respectively.

Melittin Constrains the Expression of Identified Key Genes Associated with Bladder Cancer.

This work is aimed at investigating the effect of melittin on identified key genes in bladder cancer (BC) and further providing a theoretical basis for BC treatment. GSE35014 downloaded from the Gene Expression Omnibus (GEO) database was used to screen differentially expressed genes (DEGs) in BC cells and control. Results showed that a total of 389 upregulated and 169 downregulated genes were identified. Subsequently, GO analysis, KEGG pathway enrichment analysis, and PPI network analysis were employed to disclose the crucial genes and signaling pathways involved in BC. Fifteen module-related DEGs and their associated signaling pathways were obtained according to the PPI network and modular analyses. Based on the analysis of articles retrieved in the PubMed database, we found that melittin could induce apoptosis and constrain the progression of tumor cells as a result of regulating critical cancer-related signaling pathways, such as PI3K-Akt and TNF signaling pathways. Furthermore, PI3K-Akt and TNF signaling pathways were also found to be associated with module-related DEGs according to biological analyses. At last, qRT-PCR analysis demonstrated that melittin could constrain the expression of module-related DEGs (LPAR1, COL5A1, COL6A2, CXCL1, CXCL2, and CXCL3) associated with PI3K-Akt and TNF signaling pathways in BC cells. Functional assays revealed that melittin could constrain the proliferative and migrated abilities of BC cells. Conjointly, these findings provide a theoretical basis for these six genes as drug-sensitive markers of melittin in BC treatment.

Associations Between Copper and Zinc and Risk of Hypertension in US Adults.

Evidence linking copper and zinc to hypertension are limited and conflicting. Data from the National Health and Nutrition Examination Survey (NHANES) 2007-2014 were used. Zinc and copper intake from diet and supplements was assessed with 24-h dietary recall. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg/diastolic blood pressure (DBP) ≥ 90 mmHg/treatment with hypertensive medications. In a sensitivity analysis, according to the 2017 American College of Cardiology and American Heart Association guideline, hypertension was also defined as SBP ≥ 130 mmHg/DBP ≥ 80 mmHg/treatment with hypertensive medications. A total of 17,811 adults (8430 men and 9381 women) were included. After adjustment for age, gender, body mass index (BMI), race, educational level, smoking status, family income, and total daily energy intake, the OR of hypertension for highest vs. lowest quartile intake of copper, zinc, and copper/zinc ratio was 1.11 (0.90-1.37), 1.11 (0.90-1.35), and 0.95 (0.81-1.11), respectively. In stratified analysis by BMI (< 25 kg/m2, 25-30 kg/m2, > 30 kg/m2), no significant association was found between hypertension and intakes of copper, zinc, and copper/zinc ratio (highest vs. lowest quartile) in multivariate analysis. In multivariate analysis, the OR of hypertension for highest vs. lowest quartile levels of serum copper, zinc, and copper/zinc ratio was 1.11 (0.61-2.04), 1.43 (0.84-2.44), and 0.68 (0.34-1.33), respectively. Similar results were found in the sensitivity analysis. Zinc and copper might be not independently associated with hypertension in US adults.

A 0.2 V Micro-Electromechanical Switch Enabled by a Phase Transition.

Micro-electromechanical (MEM) switches, with advantages such as quasi-zero leakage current, emerge as attractive candidates for overcoming the physical limits of complementary metal-oxide semiconductor (CMOS) devices. To practically integrate MEM switches into CMOS circuits, two major challenges must be addressed: sub 1 V operating voltage to match the voltage levels in current circuit systems and being able to deliver at least millions of operating cycles. However, existing sub 1 V mechanical switches are mostly subject to significant body bias and/or limited lifetimes, thus failing to meet both limitations simultaneously. Here 0.2 V MEM switching devices with ≳106 safe operating cycles in ambient air are reported, which achieve the lowest operating voltage in mechanical switches without body bias reported to date. The ultralow operating voltage is mainly enabled by the abrupt phase transition of nanolayered vanadium dioxide (VO2 ) slightly above room temperature. The phase-transition MEM switches open possibilities for sub 1 V hybrid integrated devices/circuits/systems, as well as ultralow power consumption sensors for Internet of Things applications.