The effects of long- and short-term interdisciplinary treatment approaches in women with fibromyalgia: a randomized controlled trial

We investigated the effects of long- and short-term interdisciplinary treatment approaches for reducing symptoms and improving health-related quality of life (HRQoL) and physical functions of patients with fibromyalgia and compared the effects of two different interdisciplinary treatment approaches. We conducted a prospective, randomized, controlled trial involving 66 women with fibromyalgia eligible for the study at a university hospital setting. The patients were randomized into three groups (allocation ratio 1:1:1) using a computer-generated random numbers: a long-term interdisciplinary treatment group (LG, n = 22) that participated in 10 sessions (3-h once-weekly session for 10 weeks) of cognitive behavioral therapy (CBT) together with exercise training and other fibromyalgia related educational programs (two full days); a short-term interdisciplinary treatment group (SG, n = 22) that received two full days of educational, exercise, and CBT programs; and a control group (CG, n = 22). The patients were evaluated at baseline and 6 months after treatment using the visual analog scale (pain, fatigue, and sleep), Fibromyalgia Impact Questionnaire, Beck Depression Inventory, Short Form-36, tender point numbers, and pressure algometry as primary outcomes. The statistical analysis was confined to the ‘per-protocol’ set. No blinding was performed. The number of patients analyzed was 21 in the LG, 19 in the SG, and 19 in the CG. The intensity of pain (p < 0.001), severity of fatigue (p = 0.048), number of tender points (p = 0.002), and pressure pain threshold (p = 0.012) decreased significantly in both the LG and SG groups compared with controls. Moreover, physical functions (p = 0.017) and physical components of the HRQoL (p = 0.036) improved significantly in the intervention groups compared with the controls. However, there was no significant difference between intervention groups and the control group at the end of study in terms of quality of sleep (p = 0.055), severity of depressive symptoms (p = 0.696), and mental components of the HRQoL (p = 0.229). Finally, with the exception of the severity of fatigue and physical components of the HRQoL, there was no obvious significant difference between the efficacies of the two treatment approaches when compared with controls; the long-term treatment was found more effective in reducing pain than the short-term. Both, long- and short-term interdisciplinary treatments were effective in reducing the severity of some symptoms and disease activity in patients with fibromyalgia. The short-term program well meets the needs of women with fibromyalgia particularly in relation to pain and health status as measured using FIQ; however, a long-term program may be beneficial in reducing fatigue and improving physical function to a higher extent.     

Gossypol stimulates opening of a Ca2+‐ and Na+‐permeable but Ni2+‐ and Co2+‐impermeable pore in bEND.3 endothelial cells

Gossypol, a polyphenolic dialdehyde toxin isolated from cotton seed, has anti‐cancer properties and has recently shown some success in the treatment of glioma. Its effects on brain neurons and blood vessels are poorly understood. In this work we examined the effects of gossypol on cytosolic Ca²⁺ concentration ([Ca²⁺]_i) of mouse brain bEND.3 endothelial cells. Cell viability tests revealed that after 3 hour and 18 hour exposures, 10 µmol/L gossypol caused 23% and 65% cell death, respectively; 3 µmol/L gossypol caused no and 21% cell death, respectively. [Ca²⁺]_i was raised concentration‐dependently by 1‐10 µmol/L gossypol. We then explored the Ca²⁺ signalling triggered by 3 µmol/L gossypol, which inflicted minimal toxicity: the Ca²⁺ signal was composed largely of Ca²⁺ influx and to a small extent, intracellular Ca²⁺ release. Such Ca²⁺ influx was much larger than store‐operated Ca²⁺ influx triggered by maximal Ca²⁺ pool depletion. The Ca²⁺ influx triggered by 3 and 10 µmol/L gossypol caused NO release and cell death, respectively. Gossypol also triggered influx of Mn²⁺ and Na⁺, but not Ni²⁺ and Co²⁺. Gossypol‐triggered Ca²⁺ signal was inhibited only by 14% and 37% by 100 µmol/L La³⁺ and 10 µmol/L nimodipine, respectively; and not suppressed at all by 5 mmol/L Ni²⁺. Gossypol‐triggered Ca²⁺ signal was suppressed by 78% by 30 µmol/L ruthenium red, suggesting gossypol may act on TRPV channels. Our results suggest gossypol triggered opening of a non‐selective cation pore, possibly a member of the TRPV family.     

Salbutamol‐induced Decrease in Augmentation Index is Related to the Parallel Increase in Heart Rate

The change in augmentation index following salbutamol inhalation has been applied to evaluate endothelial function. We examined the contribution of salbutamol‐induced increase in heart rate to the observed decrease in augmentation index. Haemodynamics were recorded using whole‐body impedance cardiography and continuous pulse wave analysis from tonometric radial blood pressure. All subjects (n = 335, mean age 46, body mass index 26, 48% men) were without medications with cardiovascular influences. The effects of salbutamol inhalation (0.4 mg) versus the endothelium‐independent agent nitroglycerin resoriblet (0.25 mg) were examined during passive head‐up tilt, as the haemodynamic influences of these compounds depend on body position. Salbutamol decreased augmentation index by ~3‐4% units in supine and upright positions. Although salbutamol moderately increased cardiac index (+4.5%) and decreased systemic vascular resistance (?8.5%), the significant haemodynamic explanatory factors for decreased augmentation index in multivariate analysis were increased supine heart rate, and increased upright heart rate and decreased ejection duration (p < 0.001 for all, r² = 0.36–0.37). Sublingual nitroglycerin decreased supine and upright augmentation index by ~15% units and ~23% units, respectively. The haemodynamic explanatory factors for these changes in multivariate analysis were increased heart rate, reduced ejection duration and reduced systemic vascular resistance (p ≤ 0.021 for all, r² = 0.22–0.34). In conclusion, the lowering influence of salbutamol on augmentation index may be largely explained by increased heart rate, suggesting that this effect may not predominantly reflect endothelial function.     

止咳平喘十二味合剂治疗痰热郁肺型咳嗽变异型哮喘临床研究

目的：观察止咳平喘十二味合剂治疗痰热郁肺型咳嗽变异型哮喘的临床疗效及其对肺功能和外周血免疫球蛋白E（IgE）、肿瘤坏死因子-α（TNF-α）、白细胞介素-8（IL-8） 的影响。方法：将2018 年9 月—2020 年8 月间由呼吸科收治且符合研究条件的咳嗽变异型哮喘患者92 例,按随机化原则分为2 组各46 例。对照组采用孟鲁司特钠联合多索茶碱治疗,观察组在对照组治疗方案的基础上联合止咳平喘十二味合剂治疗,2 组均治疗2 周,比较2 组治疗前后咳嗽症状积分、咳嗽相关生活质量评分、肺功能指标及外周血IgE、TNF-α、IL-8。结果：治疗2 周后,观察组咳嗽症状积分低于对照组（P＜0.05）;咳嗽相关生活质量评分高于对照组（P＜0.05）,观察组肺功能指标第1 秒用力呼气容积（FEV1）、呼气峰值流速（PEF） 及用力呼气中期流速（MMEF75/25） 值均高于对照组（P＜0.05）,观察组外周血IgE、TNF-α、IL-8 均低于对照组（P＜0.05）。结论：止咳平喘十二味合剂可显著降低痰热郁肺型咳嗽变异型哮喘患者外周血IgE、TNF-α 和IL-8 等炎症因子水平,改善肺功能,减轻咳嗽症状,提高咳嗽相关生活质量。     

A nomogram for predicting brain metastases of EGFR-mutated lung adenocarcinoma patients and estimating the efficacy of therapeutic strategies

BackgroundTo establish a nomogram for predicting the outcome of EGFR-mutated lung adenocarcinoma patients with brain metastases (BMs) and to estimate the efficacy of different therapeutic strategies.MethodsThe data of 129 cases with BM from the period between January 1st 2011 and December 31st 2014 were collected, and all of the cases were pathologically confirmed to be lung adenocarcinoma, stages I–IV and with 19 and/or 21 exon mutations of EGFR. Cox regression analysis and log-rank test were used for data analysis. The nomogram was used to establish the progression models.ResultsIn the univariate analysis, the stage, ECOG score, interval between the diagnosis of lung cancer and BM, the number of brain metastatic lesions, and the diameter of the maximal brain metastatic lesion correlated well with overall survival (OS). In multivariate Cox proportional hazard analysis, the ECOG score, interval between the diagnosis of lung cancer and BM, and the number of brain metastatic lesions correlated well with the OS. Patients were divided into the poor prognostic group and the good prognostic group based on the nomogram prognostic model score. Subgroup analysis showed that in the poor prognostic group, the OS of patients who received radiotherapy was better than that of the patients who did not receive radiotherapy as the first-line treatment (30 vs. 19 months, P<0.05). The OS was 30 months in the TKI subgroup and 21 months in the no TKI subgroup, but no statistical difference was found (P>0.05). Patients in the good prognostic group who received radiotherapy had a better 3-y OS rate than the patients who received no radiotherapy as the first-line treatment (91.2% vs. 58.1%, P<0.05). The 3-y OS rate was 87.6% in the TKI subgroup and 67.8% in the no TKI group (P<0.05).ConclusionsWe established an effective nomogram model to predict the progression of EGFR-mutated lung adenocarcinoma patients with BM and the therapeutic effect of the individual treatments. Radiotherapy was beneficial for the patients of both the poor and good prognostic groups, but TKI may be better suited for treating the patients with good prognosis.     

Bex2 Controls Proliferation of Human Glioblastoma Cells Through NF-κB Signaling Pathway

Glioblastoma is the most common and fatal human brain malignancy in adults with highly proliferative capacity. Despite advances in surgery and adjuvant therapy, the median survival of patients has changed little over recent decades. Identifying molecules critical for glioma development is significant for devising effective targeted therapy. We previously reported that Bex2, a member of the brain expressed X-linked gene family, promoted the progression of glioma by promoting cell proliferation. In the present study, we investigated the main mechanism of Bex2 promoting the proliferation of glioblastoma cells. We found that Bex2 downregulation inhibited glioma cell proliferation and the expression of NF-κB p65, but Bex2 overexpression promoted them. Similarly, the proliferation of glioma cells was inhibited by p65 downregulation but increased by p65 overexpression. In addition, Bex2 overexpression-induced cell proliferation was abolished by p65 downregulation. Furthermore, Bex2 with nuclear localization signal deleted no longer promoted p65 expression. In conclusion, this study demonstrates that Bex2 promotes proliferation of human glioblastoma cells via NF-κB signaling pathway and Bex2 nuclear location is critical for p65 expression.     

Prevalence of human papillomavirus infection in esophageal and cervical cancers in the high incidence area for the two diseases from 2007 to 2009 in Linzhou of Henan Province,Northern China

The etiological role of human papillomavirus (HPV) in cervical cancer has been well established. However, it is inconclusive whether HPV plays the same role in esophageal carcinogenesis. In this study, we detected HPV infection in 145 frozen esophageal tissues, including 30 normal epithelium (ENOR), 37 dysplasia (DYS) and 78 invasive squamous cell carcinoma (ESCC), and in 143 frozen cervical tissues composed of 30 normal epithelium (CNOR), 38 intraepithelial neoplasia (CIN) and 75 invasive squamous cell carcinoma (CSCC). The patients and symptom-free subjects enrolled in this study were from a high-incidence area for both ESCC and CSCC, Linzhou City, Northern China, from 2007 to 2009. The HPV infection analysis was conducted by using an HPV GenoArray Test Kit. We found that the high-risk HPV types accounted for more than 90 % of the HPV-positive lesions of esophagus and cervix tissues. The prevalence of high-risk HPV types increased significantly during the progression of both esophageal and cervical carcinogenesis (positive rate in esophageal tissues: 33 % ENOR, 70 % in DYS and 69 % in ESCC; positive rate in cervical tissues: 27 % in CNOR, 82 % in CIN and 88 % in CSCC; P < 0.001, respectively). Infection with the high-risk HPV types increased the risk for both DYS and ESCC by 4-fold (DYS vs. ENOR: OR = 4.73, 95 %CI = 1.68-13.32; ESCC vs. ENOR: OR = 4.50, 95 %CI = 1.83-11.05) and increased the risk for both CIN and CSCC by 12-fold and 20-fold (CIN vs. CNOR: OR = 12.18, 95 %CI = 3.85-38.55; CSCC vs. CNOR: OR = 20.17, 95 %CI = 6.93-58.65), respectively. The prevalence of high-risk types in ESCC patients was lower than that in CSCC patients (P = 0.005) and was significantly associated with the degree of ESCC tumor infiltration (P = 0.001). HPV 16 was the most prevalent subtype in both esophageal and cervical tissues. Single HPV infection increased significantly along with the progression of ESCC and maintained a high level in cervical tissues, regardless of whether they were CNOR or CSCC tissues. Our results showed that infection with HPV, especially the high-risk types, was positively associated with both esophageal and cervical cancers, suggesting that HPV also plays a role in the etiology of ESCC in the high-incidence area.     

Vocal pattern detection of depression among older adults

Depression is a serious problem for many older adults but is too often undetected by the person, family or providers. Although vocal patterns have been successfully used to detect and predict depression in adults aged 18 to 65 years, no studies to date have included older adults. The study purpose was to determine whether vocal patterns associated with clinical depression in younger people also signify depression in older adults. An observational, repeated measures design was used to enroll 46 volunteer older adults who completed a semi‐structured interview composed the 9‐item Patient Health Questionnaire or PHQ‐9 depression scale and selected speech measures. Recorded interviews were analysed by machine learning algorithms to evaluate whether vocal patterns may predict presence of depression in older adults. In this study, using the PHQ‐9 and a supervised machine learning algorithm accurately predicted high and low depression scores between 86% and 92% of the time. Change in raw PHQ‐9 scores between interview cycles was predicted within 1.17 points. These results provide strong and promising evidence that vocal patterns can be used effectively to detect clinical depression in adults who are 65 years and older.