Selenium maintains intestinal epithelial cells to activate M2 macrophages against deoxynivalenol injury.

Selenium (Se) is indispensable in alleviating various types of intestinal injuries. Here, we thoroughly investigated the protective effect of Se on the regulation of the epithelial cell-M2 macrophages pathway in deoxynivalenol (DON)-induced intestinal damage. In the present study, Se has positive impacts on gut health by improving gut barrier function and reducing the levels of serum DON in vivo. Furthermore, our study revealed that Se supplementation increased the abundances of GPX4, p-PI3K, and AKT, decreased the levels of 4-HNE and inhibited ferroptosis. Moreover, when mice were treated with DON and Fer-1(ferroptosis inhibitor), ferroptosis was suppressed and PI3K/AKT pathway was activated. These results indicated that GPX4-PI3K/AKT-ferroptosis was a predominant pathway in DON-induced intestinal inflammation. Interestingly, we discovered that both the number of M2 anti-inflammatory macrophages and the levels of CSF-1 decreased while the pro-inflammatory cytokine IL-6 increased in the intestine and MODE-K cells supernatant. Therefore, Se supplementation activated the CSF-1-M2 macrophages axis, resulting in a decrease in IL-6 expression and an enhancement of the intestinal anti-inflammatory capacity. This study provides novel insights into how intestinal epithelial cells regulate the CSF-1-M2 macrophage pathway, which is essential in maintaining intestinal homeostasis confer to environmental hazardous stimuli.

Induction Toripalimab and Chemotherapy for Organ Preservation in Locally Advanced Laryngeal and Hypopharyngeal Cancer: A Single-Arm Phase II Clinical Trial.

PURPOSE: The aim of this study was to assess the efficacy, toxicities, and potential role of larynx preservation of induction chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitor in locally advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: This is a single-arm phase II study. Patients with histopathologically confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma and Eastern Cooperative Oncology Group Performance Status 0-1 were eligible. Three cycles of induction chemotherapy (paclitaxel 175 mg/m2 d1, cisplatin 25 mg/m2 d1-3) combined with PD-1 inhibitor (toripalimab 240 mg d0) were administered. Response assessment was performed after induction chemoimmunotherapy using RECIST 1.1 criteria. Patients with a complete/partial response of the primary tumor received concurrent chemoradiation, followed by maintenance therapy of toripalimab. Otherwise, patients were referred to surgery, followed by adjuvant (chemo) radiation and maintenance therapy of toripalimab. The primary endpoint is a larynx preservation rate at 3 months postradiation. RESULTS: Twenty-seven patients were enrolled. Most cases exhibited stage IV disease (81.5%), with T4 representing 37.0%. Five patients underwent pretreatment tracheostomy because of impaired larynx function. Overall response rate of induction chemoimmunotherapy was 85.2%. At 3 months postradiation, the larynx preservation rate was 88.9%. With a median follow-up of 18.7 months, the 1-year overall survival rate, progression-free survival rate, and larynx preservation rate were 84.7%, 77.6%, and 88.7%, respectively. When excluding those with pretreatment tracheostomy, the 1-year larynx preservation rate was 95.5%. Exploratory analysis revealed that relapse correlated with enrichment of RNA signature of hypoxia and M2 macrophage-associated genes. CONCLUSIONS: Induction toripalimab combined with chemotherapy provided encouraging activity, promising larynx preservation rate and acceptable toxicity in this cohort of extensively locally advanced laryngeal and hypopharyngeal cancer.

Baicalin attenuated metabolic dysfunction-associated fatty liver disease by suppressing oxidative stress and inflammation via the p62-Keap1-Nrf2 signalling pathway in db/db mice.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the main cause of chronic liver disease. Baicalin (Bai), a bioactive molecule found in Scutellaria baicalensis Georgi, possesses antioxidant and antiinflammatory properties. These activities suggest Bai could be a promising therapeutic agent against NAFLD; however, its specific effects and underlying mechanism are still not clear. This study aims to explore the effect of Bai to attenuate MAFLD and associated molecular mechanisms. Bai (50, 100 or 200 mg/kg) was orally administered to db/db mice with MAFLD for 4 weeks or db/m mice as the normal control. Bai markedly attenuated lipid accumulation, cirrhosis and hepatocytes apoptosis in the liver tissues of MAFLD mice, suggesting strong ability to attenuate MAFLD. Bai significantly reduced proinflammatory biomarkers and enhanced antioxidant enzymes, which appeared to be modulated by the upregulated p62-Keap1-Nrf2 signalling cascade; furthermore, cotreatment of Bai and all-trans-retinoic acid (Nrf2 inhibitor) demonstrated markedly weakened liver protective effects by Bai and its induced antioxidant and antiinflammatory responses. The present study supported the use of Bai in attenuating MAFLD as a promising therapeutic agent, and its strong mechanism of action in association with the upregulating the p62-keap1-Nrf2 pathway.

Corrigendum: Comparative effectiveness of electroacupuncture VS neuromuscular electrical stimulation in the treatment of chronic low back pain in active-duty personals: A single-center, randomized control study.

[This corrects the article DOI: 10.3389/fneur.2022.945210.].

Comparative effectiveness of electroacupuncture VS neuromuscular electrical stimulation in the treatment of chronic low back pain in active-duty personals: A single-center, randomized control study.

Introduction: Low back pain (LBP) is the most prevalent form of chronic pain in active-duty military personnel worldwide. Electroacupuncture (EA) and neuromuscular electrical stimulation (NMES) are the two most widely used treatment methods in the military, while evidence for their benefits is lacking. The aim of this randomized clinical trial is to investigate the effectiveness of EA vs. NMES in reducing pain intensity among active-duty navy personals with chronic LBP. Methods: The study is designed as a single-center, randomized controlled trial. The primary outcome is a positive categorical response for treatment success in the first-time follow-up, which is predesignated as a two-point or greater decrease in the NRS score and combined with a score > 3 on the treatment satisfaction scale. The secondary outcomes include pain intensity, rate of treatment success, and Oswestry Disability Index (ODI) fear-avoidance beliefs questionnaire (FABQ) score along with muscular performance. The first follow-up starts on the first day after completing the last treatment session, and then the 4-weeks and 12-weeks follow-up are applied via telephone visit. Results: Eighty-five subjects complete the treatment diagram and are included in the analysis. For the primary outcome, no difference has been found between EA and NMES, with 65.1% (28 in 43) individuals reporting a positive response to EA treatment, while 53.5% (23 in 43) in NMES. However, for longer follow-ups, superiority in positive response of EA has been found in 4-weeks (26 in 39, 66.7% vs. 16 in 40, 40%; P = 0.018) and 12-weeks (24 in 36, 66.7% vs. 12 in 36, 33.3%; P = 0.005) follow-up. In the regression analysis, baseline pain intensity and FABQ score are identified to be highly associated with positive treatment outcomes. Finally, the subgroup analysis suggests that EA treatment is associated with better long-term outcomes in patients with LBP with a severe pain score (NRS score >4, Figure 4B) and stronger fear-avoidance beliefs. Conclusion: Both the EA and NMES are associated with a positive response in treating military LBP, and the former offers lasting benefits in the later follow-ups. Thus, electroacupuncture is a more recommended treatment for military LBP. A lot of research is needed to verify an efficient and standardized treatment session, with more information and evidence about indications for these treatments. Trial registration: ChiCTR, (ChiCTR2100043726); registered February 27, 2021.

Association between Exercise and Blood Pressure in Hypertensive Residents: A Meta-Analysis.

BACKGROUND: Exercise is recommended as an effective lifestyle behaviour for adults to prevent and treat hypertension. In this study, a randomized-effect meta-analysis was used to analyse the influence of exercise interventions on blood pressure in patients with hypertension. METHODS: Candidate papers were retrieved from PubMed, Web of Science, Embase, and Cochrane Library electronic databases, and 46 studies were finally included and analysed. RESULTS: It was shown that preplanned walking (systolic blood pressure (SBP): WMD (weighted mean difference) = -5.94, 95% CI: -8.57, -3.30; diastolic blood pressure (DBP): WMD = -2.66, 95% CI: -3.66, -1.67), yoga (SBP: WMD = -5.09, 95% CI: -9.28, -0.89; DBP: WMD = -3.06, 95% CI: -5.16, -0.96), aquatic sports (SBP WMD = -7.53, 95% CI: -11.40, -3.65; DBP: WMD = -5.35, 95% CI: -9.00, -1.69), and football (SBP: WMD = -6.06, 95% CI: -9.30, -2.82; DBP: WMD = -5.55, 95% CI: -8.98, -2.13) had significant effects on blood pressure reduction. However, Tai Chi (SBP: WMD = -8.31, 95% CI: -20.39, 3.77; DBP: WMD = -3.05, 95% CI: -6.96, 0.87) and Qigong (SBP: WMD = -4.34, 95% CI: -13.5, 4.82; DBP: WMD = -3.44, 95% CI: -7.89, 1.01) did not significantly reduce blood pressure. The heterogeneity of the meta-analysis was high. CONCLUSION: Walking, yoga, aquatic sports, and football were feasible and independent lifestyle interventions, and they were effective options for treating hypertension. More scientifically designed randomized controlled trials are needed in the future to further compare different forms of exercise for the treatment of hypertension.

Eighteen structurally diversified sesquiterpenes isolated from Pogostemon cablin and their inhibitory effects on nitric oxide production.

Five new sesquiterpenes, namely, guaianes A-E (1-5), including one novel carbon skeleton guaiane-type sesquiterpene derivatives (1), together with thirteen known compounds (6-18), were isolated from the aerial parts of Pogostemon cablin (Blanco.) Benth. Their chemical structures were mainly established through the relative spectroscopic data, while the absolute configurations of compounds 1-5 were elucidated on the base of single-crystal X-ray diffraction analysis and electronic circular dichroism (ECD) calculations. All compounds were tested for their inhibiting effects on NO production in LPS-stimulated BV2 microglia cells as well as the cell viabilities. The results showed that compounds 2-16 and 18 possessed moderately anti-inflammatory activities at a concentration of 50 µM.

Coffee consumption and risk of heart failure in the Physicians' Health Study.

BACKGROUND: Previous studies have reported the benefits of coffee consumption on diabetes, stroke, hyperlipidemia, and coronary artery disease (CAD). However, no large-scale long-term prospective study has evaluated the relation between coffee consumption and heart failure (HF) among US population. OBJECTIVE: To test the hypothesis that coffee consumption is associated with risk of HF among male physicians. METHODS: We prospectively studied 20,433 middle-aged and older men from the Physicians' Health Study (PHS). Coffee consumption was assessed using a semi-quantitative food frequency questionnaire. The incidence of HF was assessed based on self-reports on annual questionnaires which were validated in a subsample using by review of medical records. We used Cox proportional hazard models to compute the hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). RESULTS: The mean (SD) age of men was 66.4 (9.2) years. During a mean follow-up of 9.3 years, 901 new cases of HF were reported. In a multivariable Cox model adjusting for age, alcohol, smoking, and exercise, the HR (95% CI) of HF were 1.00 (reference), 1.04 (0.84-1.28), 0.90 (0.73-1.11), and 1.09 (0.91-1.30) for coffee consumption of almost never, <1 cup/day, 1 cup/day, and ≥2 cups/day, respectively (P for linear trend - 0.47). In a secondary analysis, dietary caffeine intake was not associated with HF risk: multivariable adjusted HR (95% CI) were 1.00 (reference), 1.07 (0.87-1.31), 0.95 (0.77-1.18), 1.06 (0.86-1.31), and 1.15 (0.92-1.44) across consecutive quintiles of dietary caffeine (P for linear trend - 0.34). CONCLUSIONS: We found no association between either coffee consumption or dietary caffeine intake with HF risk among US male physicians.

Acupuncture for Cancer-Induced Bone Pain in Animal Models: A Systemic Review and Meta-Analysis.

BACKGROUND: Cancer-induced bone pain (CIBP) is a highly prevalent symptom, which afflicts vast majority of patients who suffer from cancer. The current treatment options failed to achieve satisfactory effect and the side effects were prominent. Recent randomized controlled trials (RCTs) of animal demonstrate the benefit of acupuncture for CIBP. We sought to determine if the pooled data from available RCTs supports the use of acupuncture for CIBP. METHODS: A literature search for randomized controlled trials was conducted in six electronic databases from inception to May 31, 2019. Meta-analysis was performed with Review Manager 5.3 software; the publication bias was assessed by Stata 12.0 software. We used random effects model for pooling data because heterogeneity is absolute among studies to some extent. RESULTS: Twenty-four trials were included in the review, of which 12 trials provided detailed data for meta-analyses. Preliminary evidence indicates that compared to wait list/sham group, acupuncture was effective on increasing paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). Compared to medicine, acupuncture was less effective on PWT, but as effective as medicine on PWL. Acupuncture can reinforce medicine's effect on PWT and PWL. Compared to the control group, acupuncture was superior to increase body weight (BW), decrease spinal cord glial fibrillary acidic protein (GFAP), and interleukin-1ß (IL-1ß). Furthermore, some studies showed acupuncture delay or partially reverse morphine tolerance. Three studies found acupuncture has no effect on PWT, but 2 of them found acupuncture could enhance small dose of Celebrex's effect on CIBP. CONCLUSIONS: Acupuncture was superior to wait list/sham acupuncture on increasing PWT and has no less effect on increasing PWL compared to medicine; acupuncture improved the efficacy of drugs, increased the CIBP animals' body weight, and decreased their spinal cord GFAP and IL-1ß. High-quality studies are necessary to confirm the results.

Coffee Consumption and Risk of Atrial Fibrillation in the Physicians' Health Study.

Background Although coffee consumption is often reported as a trigger for atrial fibrillation (AF) among patients with paroxysmal AF, prospective studies on the relation of coffee consumption with AF risk have been inconsistent. Hence, we sought to assess the association between coffee consumption and risk of AF in men. Methods and Results We prospectively studied men who participated in the Physicians' Health Study (N=18 960). Coffee consumption was assessed through self-reported food frequency questionnaires. The incidence of AF was assessed through annual questionnaires and validated through review of medical records in a subsample. Cox proportional hazard models were used to calculate hazard ratios and 95% CIs of AF. The average age was 66.1 years. A total of 2098 new cases of AF occurred during a mean follow-up of 9 years. Hazard ratios (95% CI) of AF were 1.0 (reference), 0.85 (0.71-1.02), 1.07 (0.88-1.30), 0.93 (0.74-1.17), 0.85 (0.74-0.98), 0.86 (0.76-0.97), and 0.96 (0.80-1.14) for coffee consumption of rarely/never, ≤1 cup/week, 2 to 4 cups/week, 5 to 6 cups/week, 1 cup/day, 2 to 3 cups/day, and 4+ cups/day, respectively; adjusting for age, smoking, alcohol intake, and exercise (P for nonlinear trend=0.01). In a secondary analysis the multivariable adjusted hazard ratio (95% CI) of AF per standard deviation (149-mg) change in caffeine intake was 0.97 (0.92-1.02). Conclusions Our data suggest a lower risk of AF among men who reported coffee consumption of 1 to 3 cups/day.

Lack of Association Between Heart Failure and Incident Cancer.

BACKGROUND: Several recent studies have suggested an increased cancer risk among patients with heart failure (HF). However, these studies are constrained by limited size and follow-up, lack of comprehensive data on other health attributes, and adjudicated cancer outcomes. OBJECTIVES: This study sought to determine whether HF is associated with cancer incidence and cancer-specific mortality. METHODS: The study assembled a cohort from the Physicians' Health Studies I and II, 2 randomized controlled trials of aspirin and vitamin supplements conducted from 1982 to 1995 and from 1997 to 2011, respectively, that included annual health evaluations and determination of cancer and HF diagnoses. In the primary analysis, the study excluded participants with cancer or HF at baseline and performed multivariable-adjusted Cox models to determine the relationship between HF and cancer, modeling HF as a time-varying exposure. In a complementary analysis, the study used the landmark method and identified cancer-free participants at 70 years of age, distinguishing between those with and without HF, and likewise performed Cox regression. Sensitivity analyses were performed at 65, 75, and 80 years of age. RESULTS: Among 28,341 Physicians' Health Study participants, 1,420 developed HF. A total of 7,363 cancers developed during a median follow-up time of 19.9 years (25th to 75th percentile: 11.0 to 26.8 years). HF was not associated with cancer incidence in crude (hazard ratio: 0.92; 95% confidence interval: 0.80 to 1.08) or multivariable-adjusted analysis (hazard ratio: 1.05; 95% confidence interval: 0.86 to 1.29). No association was found between HF and site-specific cancer incidence or cancer-specific mortality after multivariable adjustment. Results were similar when using the landmark method at all landmark ages. CONCLUSIONS: HF is not associated with an increased risk of cancer among male physicians.

Glutathione Supplementation Attenuates Oxidative Stress and Improves Vascular Hyporesponsiveness in Experimental Obstructive Jaundice.

We investigated the protective effects and mechanism of glutathione (GSH) on vascular hyporesponsiveness induced by bile duct ligation (BDL) in a rat model. Seventy-two male Sprague-Dawley rats were randomly divided into four groups: a NS group, a GSH group, a BDL + NS group, and a BDL + GSH group. GSH was administrated into rats in the GSH and BDL + GSH groups by gastric gavage. An equal volume of normal saline was, respectively, given in the NS group and BDL + NS group. Blood was gathered for serological determination and thoracic aorta rings were isolated for measurement of isometric tension. Obstructive jaundice led to a significant increase in the serum total bilirubin, AST, and ALT levels. The proinflammatory cytokines levels (TNF-α and IL-1ß), concentration of NO, and oxidative stress markers (MDA and 3-NT) were increased as well. All of those were reduced by the treatment of GSH. Meanwhile, contraction of aorta rings to NA and vasorelaxation to ACh or SNP in the BDL group rats were markedly decreased, while GSH administration reversed this change. Our findings suggested that GSH supplementation attenuated overexpressed ONOO(-) from the reaction of excessive NO with O2 (∙-) and protected against obstructive jaundice-induced vascular hyporesponsiveness in rats.

Regional differences in health status in China: population health-related quality of life results from the National Health Services Survey 2008.

PURPOSE: To measure, describe and analyse regional differences in health-related quality of life measured by EQ-5D in China. Data were obtained via face-to-face interviews on a national representative sample (n=120,703, 15-103 years). The EQ-5D instrument was used to measure health status. RESULTS: Rural areas had worse health status than urban areas. Health status was worst in western areas and best in eastern areas, and such disparities were profounder in rural areas. In urban areas, health status was best in middle-sized cities. In rural areas, health status increased with the economic development level of a county. CONCLUSION: Our study enhances understanding of the urban-rural differences and east-middle-west differences in health and sheds light on inequalities in health status between different city categories in the urban areas and county categories in the rural areas.