Long-term di-(2-ethylhexyl) phthalate exposure reduces sorafenib treatment efficacy by enhancing mesenchymal transition in hepatocellular carcinoma.

Di(2-ethylhexyl) phthalate (DEHP) is a worldwide common plasticizer. Nevertheless, DEHP is easily leached out to the environment due to the lack of covalent bonds with plastic. High dose of DEHP exposure is often observed in hemodialysis patients because of the continual usage of plastic medical devices. Although the liver is the major organ that catabolizes DEHP, the impact of long-term DEHP exposure on the sensitivity of liver cancer to chemotherapy remains unclear. In this study, we established long-term DEHP-exposed hepatocellular carcinoma (HCC) cells and two NOD/SCID mice models to investigate the effects and the underlying mechanisms of long-term DEHP exposure on chemosensitivity of HCC. The results showed long-term DEHP exposure potentially increased epithelial-mesenchymal transition (EMT) in HCC cells. Next generation sequencing showed that long-term DEHP exposure increased cell adhesion/migratory related genes expression and blunted sorafenib treatment induced genes alterations. Long-term exposure to DEHP reduced the sensitivity of HCC cells to sorafenib-induced anti-migratory effect by enhancing the EMT transcription factors (slug, twist, and ZEB1) and mesenchymal protein (vimentin) expression. In NOD/SCID mice model, we showed that long-term DEHP-exposed HCC cells exhibited higher growth rate. Regarding the anti-HCC effects of sorafenib, subcutaneous HuH7 tumor grew slowly in sorafenib-treated mice. Nonetheless, the anti-tumor growth effect of sorafenib was not observed in long-term DEHP-exposed mice. Higher mesenchymal markers and proliferating cell nuclear antigen (PCNA) expression were found in sorafenib-treated long-term DEHP-exposed mice. In conclusion, long-term DEHP exposure promoted migratory activity in HCC cells and decreased sorafenib sensitivity in tumor-bearing mice.

Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 3: Alleviation of hypoxia, muscle-wasting, and modulation of redox functions in amyotrophic lateral sclerosis.

OBJECTIVE: The aim of this clinical study is to obtain evidence for the clinical efficacy of Bu-Shen-Jian-Pi formula (BSJP), a traditional Chinese medicine, used for the treatment of amyotrophic lateral sclerosis, a relatively rare, progressive and usually fatal disease possibly associated with alterations in tissue redox status, hypoxia, and muscular injury. BACKGROUND: The active agents in BSJP formula† causing apoptosis, modulation of redox changes, and alterations in the immune status have been studied previously by us using cell cultures. The findings from these investigations have been incorporated into pharmacology databases employed in our analysis of BSJP using network pharmacology analysis/artifical intelligence. This information has been used here in the design of the investigation and to optimize evaluation of the clinical efficacy and usefulness of this herbal medicine, as far as possible using evidence-based medicine criteria. MATERIALS AND METHODS: The design of the study was a randomized multi-center, controlled clinical trial in 127 patients with confirmed diagnoses of amyotrophic lateral sclerosis. Patients and investigator were double-blinded. Clinical efficacy was determined using the Amyotrophic Lateral Sclerosis Symptom Score in Integrative Treatment Scale (ALS-SSIT) and the Amyotrophic Lateral Sclerosis Rating Scale-Revised (ALSFRS-R), together with tests of limb muscle strength using the manual muscle test (MMT), forced vital capacity (FVC), and clinical chemistry laboratory tests over a 20-week observation period. RESULTS: The scores of ALS-SSIT in the BSJP group increased significantly (22%) after treatment. The ALSFRS-R score in the BSJP group decreased significantly after treatment (19%). The rate of decrease in muscle function (MMT score) in most BSJP patients was lower than that in the control group, where the differences in the scores for the trapezius and triceps brachii were statistically significant compared to the control group. The fall in FVC in the BJSP group was significantly slower than in the control group. There were no marked differences observed in the frequency of side effects. Serum vitamin D3 levels in the BSJP group showed greater increases compared to the control group. CONCLUSION: BSJP treatment reduced the rate of progression of amyotrophic lateral sclerosis according to the ALS-SSITS and ALSFRS scores and significantly reduced the rate of deterioration in muscle function in the limbs of amyotrophic lateral sclerosis patients. The modes of action of BSJP in treating amyotrophic lateral sclerosis are probably diverse and multi targeted, some of which may involve regulation of serum vitamin D3 and alleviation of the impairments in liver and kidney function.

Brain derived neurotrophic factor and treatment outcomes among veterans attending an intensive treatment program for posttraumatic stress disorder.

Brain derived neurotrophic factor (BDNF) may play an important role in the success of treatment for posttraumatic stress disorder (PTSD). Pre- and post-treatment blood samples were analyzed for 40 veterans who completed a 3-week intensive outpatient treatment for PTSD. The treatment included Cognitive Processing Therapy, mindfulness, and yoga as core treatment components. PTSD symptoms were assessed at pre-treatment, post-treatment, and 3-month follow-up. Participants reported large decreases in PTSD symptoms from pre-to post-treatment (d = 1.46, p < 0.001) and pre-treatment to 3-month follow-up (d = 0.91, p < 0.001). Unexpectedly, participants demonstrated a decrease in BDNF from pre-to post-treatment (d = 0.64, p < 0.001). Changes in BDNF from pre-to post-treatment were not significantly associated with PTSD symptom improvement. However, higher levels of post-treatment BDNF were significantly associated with lower PTSD symptoms at 3-month follow-up (n = 27, r = -0.57, p = 0.002) and greater improvements in PTSD symptoms from pre-treatment to 3-month follow-up (n = 27, r = 0.50, p = 0.008). Higher levels of post-treatment BDNF may facilitate the long-term success of intensive PTSD treatment. Further research with larger samples is needed to evaluate the processes by which BDNF may affect consolidation of improvements after completion of PTSD treatment.

Effectiveness of septoplasty compared to medical management in adults with obstruction associated with a deviated nasal septum: the NAIROS RCT.

Background: The indications for septoplasty are practice-based, rather than evidence-based. In addition, internationally accepted guidelines for the management of nasal obstruction associated with nasal septal deviation are lacking. Objective: The objective was to determine the clinical effectiveness and cost-effectiveness of septoplasty, with or without turbinate reduction, compared with medical management, in the management of nasal obstruction associated with a deviated nasal septum. Design: This was a multicentre randomised controlled trial comparing septoplasty, with or without turbinate reduction, with defined medical management; it incorporated a mixed-methods process evaluation and an economic evaluation. Setting: The trial was set in 17 NHS secondary care hospitals in the UK. Participants: A total of 378 eligible participants aged > 18 years were recruited. Interventions: Participants were randomised on a 1: 1 basis and stratified by baseline severity and gender to either (1) septoplasty, with or without turbinate surgery (n = 188) or (2) medical management with intranasal steroid spray and saline spray (n = 190). Main outcome measures: The primary outcome was the Sino-nasal Outcome Test-22 items score at 6 months (patient-reported outcome). The secondary outcomes were as follows: patient-reported outcomes - Nasal Obstruction Symptom Evaluation score at 6 and 12 months, Sino-nasal Outcome Test-22 items subscales at 12 months, Double Ordinal Airway Subjective Scale at 6 and 12 months, the Short Form questionnaire-36 items and costs; objective measurements - peak nasal inspiratory flow and rhinospirometry. The number of adverse events experienced was also recorded. A within-trial economic evaluation from an NHS and Personal Social Services perspective estimated the incremental cost per (1) improvement (of ≥ 9 points) in Sino-nasal Outcome Test-22 items score, (2) adverse event avoided and (3) quality-adjusted life-year gained at 12 months. An economic model estimated the incremental cost per quality-adjusted life-year gained at 24 and 36 months. A mixed-methods process evaluation was undertaken to understand/address recruitment issues and examine the acceptability of trial processes and treatment arms. Results: At the 6-month time point, 307 participants provided primary outcome data (septoplasty, n = 152; medical management, n = 155). An intention-to-treat analysis revealed a greater and more sustained improvement in the primary outcome measure in the surgical arm. The 6-month mean Sino-nasal Outcome Test-22 items scores were -20.0 points lower (better) for participants randomised to septoplasty than for those randomised to medical management [the score for the septoplasty arm was 19.9 and the score for the medical management arm was 39.5 (95% confidence interval -23.6 to -16.4; p < 0.0001)]. This was confirmed by sensitivity analyses and through the analysis of secondary outcomes. Outcomes were statistically significantly related to baseline severity, but not to gender or turbinate reduction. In the surgical and medical management arms, 132 and 95 adverse events occurred, respectively; 14 serious adverse events occurred in the surgical arm and nine in the medical management arm. On average, septoplasty was more costly and more effective in improving Sino-nasal Outcome Test-22 items scores and quality-adjusted life-years than medical management, but incurred a larger number of adverse events. Septoplasty had a 15% probability of being considered cost-effective at 12 months at a £20,000 willingness-to-pay threshold for an additional quality-adjusted life-year. This probability increased to 99% and 100% at 24 and 36 months, respectively. Limitations: COVID-19 had an impact on participant-facing data collection from March 2020. Conclusions: Septoplasty, with or without turbinate reduction, is more effective than medical management with a nasal steroid and saline spray. Baseline severity predicts the degree of improvement in symptoms. Septoplasty has a low probability of cost-effectiveness at 12 months, but may be considered cost-effective at 24 months. Future work should focus on developing a septoplasty patient decision aid. Trial registration: This trial is registered as ISRCTN16168569 and EudraCT 2017-000893-12. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/226/07) and is published in full in Health Technology Assessment; Vol. 28, No. 10. See the NIHR Funding and Awards website for further award information.

Septoplasty is an operation to straighten the septum, which is the partition wall between the nostrils inside the nose. Septoplasty can be used as a treatment for people who have a bent septum and symptoms of a blocked nose, such as difficulty sleeping and exercising. Medical management (a saltwater spray to clear the nose followed by a nose steroid spray) is an alternative treatment to septoplasty. The Nasal AIRway Obstruction Study (NAIROS) aimed to find out whether septoplasty or medical management is a better treatment for people with a bent septum and symptoms of a blocked nose. We recruited 378 patients with at least moderately severe nose symptoms from 17 hospitals in England, Scotland and Wales to take part in the NAIROS. Participants were randomly put into one of two groups: septoplasty or medical management. Participants' nose symptoms were measured both when they joined the study and after 6 months, using a questionnaire called the Sino-nasal Outcome Test-22 items. This questionnaire was chosen because patients reported that it included symptoms that were important to them. Other studies have shown that a 9-point change in the Sino-nasal Outcome Test-22 items score is significant. After 6 months, on average, people in the septoplasty group improved by 25 points, whereas people in the medical management group improved by 5 points. We saw improvement after septoplasty among patients with moderate symptoms, and among those with severe symptoms. Most patients who we spoke to after a septoplasty were happy with their treatment, but some would have liked more information about what to expect after their nose surgery. In the short term, septoplasty is more costly than medical management. However, over the longer term, taking into account all the costs and benefits of treatment, suggests that septoplasty would be considered good value for money for the NHS.

Efficacy and safety of Xiaofeng powder in the treatment of chronic urticaria: A systematic review and meta-analysis.

BACKGROUND: Chronic urticaria is a group of skin diseases characterized by pruritus and/or vascular oedema and belongs to the category of "addictive rash" in Traditional Chinese Medicine, and its aetiology is closely related to wind evil. Antihistamines are often used in treatment. Although they have certain effects, they also easily cause disease recurrence. Xiaofeng powder treats this disease has a significant effect in improving the disease state and reducing the recurrence rate. However, there is a lack of evidencebased research. This study to systematically evaluate the clinical efficacy of modified Xiaofeng powder in the treatment of chronic urticaria (CU). METHODS: Computer searches of Chinese databases such as China National Knowledge Infrastructure, China Scientific Journal Database, China Biomedical Literature Database, and WanFang Date and foreign databases such as PubMed and the Web of Science were performed. We retrieved published clinical randomized controlled trials of Xiaofeng powder in the treatment of CU from the establishment of the databases to November 2023. The data were extracted from clinical trials that met the inclusion criteria of this study, and the quality was evaluated through the Cochrane Handbook of Systematic Reviews 5.1.0. Finally, a meta-analysis was performed using RevMan 5.3 statistical software. RESULTS: A total of 11 randomized controlled trials involving 1076 patients were included. The cure rate odds ratio (OR) and 95% confidence interval (CI; shown in brackets) were 2.11 [1.45, 3.07]; the total effective rate OR and CI were 2.42 [1.60, 3.68]; the recurrence rate OR and CI were 0.22 [0.15, 0.34]; the adverse reaction rate OR and CI were 0.23 [0.12, 0.45]; and the mean weighted mean difference (MD) and 95% CI (shown in brackets) of itching degree, wind mass size, wind mass number and wind mass duration in symptom and sign integrals were -0.70 [-0.73, 0.67], -0.64 [-0.96, 0.31], , -0.72 [-1.23, 0.22], and -0.68 [-1.13, 0.23], , respectively. CONCLUSION: The clinical efficacy of modified Xiaofeng powder in the treatment of CU is better than that of antihistamine drugs, with lower adverse reaction and recurrence rates and higher safety. However, the quality of clinical research included is relatively low, and findings need to be confirmed by high-quality research.

Pediatric massage therapy for treatment of tic disorders in children: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Tic disorder is a common neurodevelopmental disorder in childhood, characterized primarily by motor or vocal tics. However, there is no systematic evaluation of pediatric massage therapy for children with Tic disorder. This study aims to evaluate the effectiveness and safety of massage therapy for children with tic disorder through a comprehensive meta-analysis and systematic review. METHODS: We systematically searched relevant randomized controlled trials from various databases such as CBM, CNKI, VIP, Wanfang database, PubMed, Embase, Web of Science, Cochrane Library, and SINOMED, published up to October 2023. To collect randomized controlled trials on pediatric massage therapy or in combination with other therapies for the treatment of tic disorders in children. The risk of bias in the included articles was assessed using the Cochrane guideline. Meta-analyses were performed using Review Manager 5.4, and publication bias was evaluated by using Begg test and Egger test in Stata SE software. RESULTS: This meta-analysis included 19 randomized controlled trials with 1423 patients. Pediatric massage therapy alone or in combination with conventional medication demonstrated a significant increase in clinical effectiveness rates [risk ratios = 1.15, 95% confidence interval [CI] (1.10, 1.20), Z = 6.54, P < .001], and reduced Yale Global Tie Severity Scale scores [standardized mean difference = -0.85, 95% CI (-1.50, -0.19), Z = 2.54, P = .01] and traditional Chinese medicine syndrome scores [standardized mean difference = -1.35, 95%CI (-2.08, -0.63), Z = 3.66, P = .0002]. In terms of adverse reactions, there was no statistical difference between the experimental and control groups [risk ratios = 0.26, 95% CI (0.14, 0.49), Z = 4.25, P < .001]. The Begg test and Egger test results indicated no publication bias. CONCLUSION: Evidence suggests that pediatric massage therapy is effective in improving tic disorders in children.

Treatments for ADHD in Children and Adolescents: A Systematic Review.

CONTEXT: Effective treatment of attention-deficit/hyperactivity disorder (ADHD) is essential to improving youth outcomes. OBJECTIVES: This systematic review provides an overview of the available treatment options. DATA SOURCES: We identified controlled treatment evaluations in 12 databases published from 1980 to June 2023; treatments were not restricted by intervention content. STUDY SELECTION: Studies in children and adolescents with clinically diagnosed ADHD, reporting patient health and psychosocial outcomes, were eligible. Publications were screened by trained reviewers, supported by machine learning. DATA EXTRACTION: Data were abstracted and critically appraised by 1 reviewer and checked by a methodologist. Data were pooled using random-effects models. Strength of evidence and applicability assessments followed Evidence-based Practice Center standards. RESULTS: In total, 312 studies reported in 540 publications were included. We grouped evidence for medication, psychosocial interventions, parent support, nutrition and supplements, neurofeedback, neurostimulation, physical exercise, complementary medicine, school interventions, and provider approaches. Several treatments improved ADHD symptoms. Medications had the strongest evidence base for improving outcomes, including disruptive behaviors and broadband measures, but were associated with adverse events. LIMITATIONS: We found limited evidence of studies comparing alternative treatments directly and indirect analyses identified few systematic differences across stimulants and nonstimulants. Identified combination of medication with youth-directed psychosocial interventions did not systematically produce better results than monotherapy, though few combinations have been evaluated. CONCLUSIONS: A growing number of treatments are available that improve ADHD symptoms and other outcomes, in particular for school-aged youth. Medication therapies remain important treatment options but are associated with adverse events.

The impact of blinding on estimated treatment effects in randomized clinical trials on acupuncture: A meta-epidemiological study.

OBJECTIVE: To evaluate the sole impact of blinding patients and outcome assessors in acupuncture randomized controlled trials (RCTs) on treatment effects while considering the type of outcome measures. METHODS: We searched databases for the meta-analyses on acupuncture with both blinded and non-blinded RCTs. Mixed-effects meta-regression models estimated the average ratio of odds ratios (ROR) and differences in standardized mean differences (dSMD) for non-blinded RCTs versus blinded mixed-effects meta-regression model. RESULTS: The study included 96 meta-analyses (1012 trials). The average ROR for lack of patient blinding was 1.08 (95% confidence intervals 0.79-1.49) in 18 meta-analyses with binary patient-reported outcomes. The average ROR for lack of outcome assessor blinding was 0.98 (0.77-1.24) in 43 meta-analyses with binary subjective outcomes. The average dSMD was -0.38 (-0.96 to 0.20) in 10 meta-analyses with continuous patient-reported outcomes. The average dSMD was -0.13 (-0.45 to 0.18) in 25 meta-analyses with continuous subjective outcomes. The results of the subgroup analysis were consistent with the primary analysis findings. CONCLUSIONS: Blinding of participants and outcome assessors does not significantly influence acupuncture treatment efficacy. It underscores the practical difficulties of blinding in acupuncture RCTs and the necessity to distinguish between trials with and without successful blinding to understand treatment expectations' effects. Enhancing blinding procedures' quality and assessment in future research is crucial for improving RCTs' internal validity and reliability.

Observation of the efficacy of elongated needle therapy in treating patients with â ¢B prostatitis of stagnant dampness-heat syndrome. / 芒针治疗湿热瘀阻证⠢Båž‹å‰åˆ—è ºç‚Žæ‚£è€ çš„ç–—æ•ˆè§‚å¯Ÿ.

OBJECTIVES: To observe the clinical efficacy in patients with ⅢB prostatitis of stagnant dampness-heat syndrome treated with elongated needle therapy. METHODS: A total of 90 patients with ⅢB prostatitis of stagnant dampness-heat syndrome were selected and randomly divided into a treatment group(45 cases, 2 dropped out) and a control group(45 cases, 1 dropped out) using a random number table method. The control group was treated with oral administration of Qianlie Shutong Capsule, 3 capsules per dose, 3 times a day for a total of 4 weeks. The treatment group received elongated needle therapy at Qihai(CV6), Zhongji(CV3), bilateral Zhibian(BL54) and Shuidao(ST28), with one treatment per day for 4 weeks. Before and after treatment, the traditional Chinese medicine syndrome score, National Institutes of Health Chronic Prostatitis Symptom Index(NIH-CPSI) score were compared between the two groups, and the clinical efficacy was compared after treatment. RESULTS: Compared with that before treatment, the control group showed significant decrease in traditional Chinese medicine syndrome score, testicular pain, urinary frequency, unending remnants of urine, scrotal wetness, yellowish urine, urinary symptoms, and quality of life scores after treatment(P<0.05)；the treatment group showed significant decrease in traditional Chinese medicine syndrome score, and perineal pain, groin pain, pelvic pain, testicular pain, scrotal wetness, yellowish urine scores, NIH-CPSI total score, pain symptoms, urinary symptoms, and quality of life scores after treatment(P<0.05). After treatment, the treatment group showed significantly lower traditional Chinese medicine syndrome score, and perineal pain, groin pain, pelvic pain, testicular pain scores, NIH-CPSI total score, pain symptoms, and quality of life scores than those of the control group(P<0.05). The effective rate in the treatment group (63.64%, 28/43) was significantly higher than that in the control group (88.37%, 38/44, P<0.05). CONCLUSIONS: Elongated needle therapy can significantly improve the traditional Chinese medicine syndrome score, NIH-CPSI total score, and pain symptom scores in patients with ⅢB prostatitis of stagnant dampness-heat syndrome. It can significantly improve the cure rate in these patients and is particularly effective in relieving pain.

Sacral neuromodulation for constipation and fecal incontinence in children and adolescents - study protocol of a prospective, randomized trial on the application of invasive vs. non-invasive technique.

BACKGROUND: A therapeutic effect of sacral neuromodulation (SNM) on fecal incontinence (FI) and quality of life has been proven in adults. SNM is, however, rarely used in pediatric cases. The aim of the study is to investigate effects of SNM in pediatric constipation in a prospective parallel-group trial. METHODS: A monocentric, randomized, unblinded, parallel-group trial is conducted. SNM is conducted in the invasive variant and in an innovative, external approach with adhesive electrodes (enteral neuromodulation, ENM). We include patients with constipation according to the ROME IV criteria and refractory to conventional options. Patients with functional constipation and Hirschsprung's disease are able to participate. Participants are allocated in a 1:1 ratio to either SNM or ENM group. Clinical data and quality of life is evaluated in regular check-ups. Neuromodulation is applied continuously for 3 months (end point of the study) with follow-up-points at 6 and 12 months. Findings are analyzed statistically considering a 5% significance level (p ≤ 0.05). Outcome variables are defined as change in (1) episodes of abdominal pain, (2) episodes of FI, (3) defecation frequency, (4) stool consistency. Improvement of proprioception, influence on urinary incontinence, quality of life and safety of treatment are assessed as secondary outcome variables. We expect a relevant improvement in both study groups. DISCUSSION: This is the first trial, evaluating effects of neuromodulation for constipation in children and adolescents and comparing effects of the invasive and non-invasive application (SNM vs. ENM). TRIAL REGISTRATION: The study is registered with clinicaltrials.gov, Identifier NCT04713085 (date of registration 01/14/2021).

Abdominal massage to prevent ileus after colorectal surgery. A single-center, prospective, randomized clinical trial: the MATRAC Trial.

BACKGROUND: There is scarce literature on the effect of mechanical abdominal massage on the duration of ileus after colectomy, particularly in the era of enhanced recovery after surgery (ERAS). The aim of this study was to determine whether abdominal massage after colorectal surgery with anastomosis and no stoma helps toward a faster return of intestinal transit. METHODS: This study was a superiority trial and designed as a prospective open-label, single-center, randomized controlled clinical trial with two parallel groups. Patients scheduled to undergo intestinal resection and follow an ERAS protocol were randomly assigned to either the standard ERAS group or the ERAS plus massage group. The primary endpoint was the return of intestinal transit, defined as the first passage of flatus following the operation. Secondary endpoints included time of the first bowel motion, maximal pain, 30 day complications, complications due to massage, anxiety score given by the Hospital Anxiety and Depression (HAD) questionnaire, and quality of life assessed by the EQ-5D-3L questionnaire. RESULTS: Between July 2020 and June 2021, 36 patients were randomly assigned to the ERAS group or the ERAS plus massage group (n = 19). Patients characteristics were comparable. There was no significant difference in time to passage of the first flatus between the ERAS group and the ERAS plus abdominal massage group (1065 versus 1389 min, p = 0.274). No statistically significant intergroup difference was noted for the secondary endpoints. CONCLUSION: Our study, despite its limitations, failed to demonstrate any advantage of abdominal massage to prevent or even reduce symptoms of postoperative ileus after colorectal surgery. TRIAL REGISTRATION NUMBER: 38RC20.021.

Bushen Formula promotes the decrease of HBsAg levels in patients with CHB by regulating Tfh cells and B-cell subsets.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Formula (BSF) is the effective traditional Chinese medicine (TCM) for chronic hepatitis B (CHB) according to our previous researches. However, the special effectiveness of BSF treating CHB patients in different stages and the immunoregulatory mechanisms remain to be explored. AIM OF THE STUDY: To compare the therapeutic effects of BSF in both treatment-naive patients and Peg-IFN-α-treated patients, and explore the potential mechanism of immunomodulation. MATERIALS AND METHODS: Ultra-high performance liquid chromatography-quadrupole electrostatic field-orbital trap high resolution mass spectrometry and the TCMSP database were used to determine the main components of BSF. Two hundred and sixty-six patients were enrolled in the retrospective study, and they were divided into the treatment group (T-Group, BSF plus Peg-IFN-α) and the control group (C-Group, Peg-IFN-α monotherapy). Within each group, patients were further grouped into subgroups, namely T1/C1 groups (treatment-naive patients, T1 = 34, C1 = 94) and T2/C2 groups (Peg-IFN-α-treated patients, T2 = 56, C2 = 82). Serum HBV markers, serum HBV DNA levels, serum ALT/AST and TCM symptoms were obtained from the record. Bioinformatics analysis was employed to obtain the potential immunoregulatory mechanisms of BSF treating CHB patients. Among patients in T2 and C2 group, peripheral mononuclear cells from 36 patients were used to analyze the characteristics of peripheral follicular helper T (Tfh) cells and B-cell subtypes by flow cytometry. Preparation of BSF-containing serum in rats. In vitro, the co-culture system of CXCR5+ cells and HepG2.2.15 cells was built to investigate the immunoregulatory effects of BSF. RESULTS: A total of 14 main active compounds were detected in BSF, which were deemed critical for the treatment of CHB. Our findings indicated that the T2-Group exhibited the higher percentage of HBsAg decline ≥ 1-log10 IU/ml and rate of HBeAg seroclearance compared to the C2-Group (35.7% vs. 15.9%, P = 0.033; 33.9% vs. 11.0%, P = 0.002). Additionally, the T2-Group demonstrated the higher percentage of HBsAg decline ≥ 1-log10 IU/ml and rate of HBeAg seroclearance compared to the T1-Group (35.7% vs. 14.7%, P = 0.031; 33.9% vs. 2.9%, P = 0.000). The total effective rate based on TCM clinical syndrome in T1-Group and T2-Group were significantly greater than those in C1-Group and C2-Group (85.3% vs. 61.7%, P = 0.012; 89.1% vs. 63.4%, P = 0.000). Bioinformatics analysis indicated that the immunoregulatory mechanisms of BSF treating CHB patients were mainly linked to the growth and stimulation of B-cell, T-cell differentiation, and the signaling pathway of the B-cell receptor. Furthermore, the frequencies of Tfh cells and its IL-21 level, and the IL-21R expressed by B-cell were all increased after BSF treatment. Additionally, in the co-culture system of CXCR5+ cells and HepG2.2.15 cells, HBsAg and HBeAg levels were decreased after BSF-containing serum treatment，as well as the up-regulating of Tfh cell frequencies and down-regulating of B-cell frequencies. CONCLUSIONS: BSF have the higher percentage of HBsAg decline and HBeAg seroclearance in Peg-IFN-α-treated patients compared with treatment-naive patients. The potential immunoregulatory mechanism may correlate with promoting the interaction between Tfh cells and B-cell through IL-21/IL-21R signaling pathway.

Efficacy of a fish hydrolysate supplement on sleep quality: A randomized, double-blind, placebo-controlled, crossover clinical trial.

BACKGROUND & AIMS: Sleep disturbances are widespread in modern societies and linked to a variety of diseases, creating an urgent need for the development of products that help combat sleep difficulties. One suitable nutritional supplement may be a fish hydrolysate composed of low molecular weight peptides. METHODS: This two-arm, double-blind, randomized, placebo-controlled crossover study investigated the effect of a 4-week fish hydrolysate intervention on sleep in a healthy German population reporting poor sleep quality, assessed with the Pittsburgh Sleep Quality Index (PSQI). Further sleep parameters were measured using an online diary and a wrist wearable device. Additionally, questionnaires related to stress, anxiety, depression, and well-being were evaluated and salivary cortisol and product satisfaction were assessed. RESULTS: The 4-week fish hydrolysate supplementation significantly improved subjective sleep quality measured with the PSQI-score (p = .002). Moreover, individuals reported improvements in sleep efficacy and a reduction in sleep disturbances and daytime sleepiness during fish hydrolysate intake (p = .013, p = .046, p = .004 respectively), but not during placebo phase (all p > .05). No significant intra-individual differences were found between fish hydrolysate and placebo supplementation (p > .05). CONCLUSIONS: Although no significant intra-individual differences were found between fish hydrolysate and placebo supplementation, the significant improvement in subjective sleep quality from baseline to treatment phase suggests that fish hydrolysate is a safe nutritional supplement to support individuals with self-reported sleep problems. CLINICAL TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov with the Identifier NCT04983355.

Transcutaneous tibial nerve stimulation in patients with multiple sclerosis and overactive bladder: a real-life clinical and urodynamic assessment.

AIMS: The aims of the present study were to assess the effectiveness of transcutaneous tibial nerve stimulation (TTNS) on overactive bladder (OAB) symptoms and on urodynamic parameters in patients with multiple sclerosis (PwMS) and to seek predictive factors of satisfaction. METHODS: All PwMS who performed 12-24 weeks of TTNS and who underwent urodynamic assessment before and after treatment between June 2020 and October 2022 were included retrospectively. Data collected were bladder diaries, symptoms assessed with Urinary Symptoms Profile (USP), and urodynamic parameters (bladder sensations, detrusor overactivity, and voiding phase). Patients with improvement rated as very good or good on Patient Global Impression of Improvement (PGI-I) score were considered as responders. RESULTS: Eighty-two patients were included (mean age: 47.1 ± 11.5 years, 67 (82%) were women). The mean USP OAB sub-score decreased from 7.7 ± 3.5 to 6.0 ± 3.4 (p < 0.0001). On bladder diaries, voided volumes, void frequency, and the proportion of micturition done at urgent need to void significantly improved with TTNS (p < 0.05). No significant change was found in urodynamic parameters. According to the PGI-I, 34 (42.5%) patients were good responders. The only parameter associated with higher satisfaction was the percentage of micturition done at urgent need to void before the initiation of the treatment (39.8% ± 30.5 in the responder group vs 25.1% ± 25.6 in the low/no responder group; p = 0.04). CONCLUSION: TTNS improves OAB symptoms in PwMS, without significant changes on urodynamics. A high rate of strong or urgent need to void in daily life was associated with higher satisfaction.

Silymarin (Milk Thistle) Treatment of Adults With Gambling Disorder: A Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Data on the pharmacological treatment of gambling disorder are limited. Silymarin (derived from milk thistle) has antioxidant properties. The goal of the current study was to determine the efficacy and tolerability of silymarin in adults with gambling disorder. METHODS: Forty-three individuals (18 [41.9%] women; mean age=49.61 [±13.1] years) with gambling disorder entered an 8-week, double-blind, placebo-controlled study. Dosing of silymarin ranged from 150 to 300 mg twice a day. The primary outcome measure was the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS). Secondary outcome measures comprised the Gambling Symptom Assessment Scale and measures of depression and anxiety. Outcomes were examined using mixed-effect models. RESULTS: Silymarin did not statistically differentiate from the placebo on any of the outcome measures of interest, in terms of treatment group×time interactions. There was a robust response in the placebo group (57% reduction on the PG-YBOCS), and on average there was a 56% reduction in YBOCS score for the milk thistle. CONCLUSIONS: The findings of this study do not support the use of silymarin/milk thistle in the treatment of gambling disorder but highlight the large placebo response seen in gambling disorder. Treatment interventions for gambling disorder need to better understand and address the placebo response. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02337634.

Whole-body and targeted narrowband ultraviolet B phototherapy effectively stabilize acral vitiligo with negligible repigmentation beyond wrists and ankles: Results from a split-body randomized controlled trial.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) phototherapy promotes stability and repigmentation in vitiligo. No studies have compared targeted NB-UVB with whole-body NB-UVB in treatment of acral vitiligo. OBJECTIVES: This randomized split-body study compared whole-body NB-UVB with targeted NB-UVB in inducing stability and repigmentation in acral vitiligo. METHODS: Thirty-two patients with bilaterally symmetrical acral vitiligo lesions (distal to elbows and knees) were recruited. Patients received whole-body NB-UVB treatment, with one hand and one foot shielded until elbow and knee, followed by targeted NB-UVB treatment on the shielded side. Patients were assessed at 4-week intervals for 24 weeks using Vitiligo Disease Activity (VIDA) score, Vitiligo Skin Activity Score (VSAS), Vitiligo Area Scoring Index (determined through fingertip method, using the method to calculate facial-VASI) and degree of repigmentation. RESULTS: After 12 weeks, 87.5% of patients achieved a VIDA score of 3, with none having active disease at 24 weeks. Over 50% repigmentation was observed in 42.2% and 37.5% of limbs in whole-body and targeted groups, respectively (p = .95). No improvement in F-VASI scores of hands and feet (distal to wrist and ankles) was noted with either modality over the 24-week period. CONCLUSION: Our study showed comparable repigmentation rates between whole-body and targeted NB-UVB groups. Limited effectiveness of phototherapy in repigmentation of hands and feet underscores an important therapeutic gap.

Daoyin therapy in chronic neck pain: study protocol for a randomized controlled trial.

BACKGROUND: Daoyin therapy (DT), an ancient therapeutic approach with a history spanning thousands of years, has traditionally been employed to address musculoskeletal pain and psychosomatic disorders. However, the application of DT for chronic neck pain (CNP) has received limited attention in the existing literature, and systematic randomized clinical trials (RCTs) in this context remain scarce. This manuscript outlines an RCT protocol designed to investigate whether DT is more effective at alleviating CNP in adult individuals compared to other interventions. METHODS: A 12-week RCT was conducted, with participants undergoing randomization into one of three groups: DT, Meditation + Fitness Exercise (M+FE), or a control group. Participants in the DT and M + FE groups attended their respective training classes three times per week for 12 weeks. Participants in the control group were required to attend health education workshops every 2 weeks. Following the 12-week intervention period, all participants underwent follow-up assessments at the 16th week. Outcome measures encompassed the Simplified Chinese Neck Pain and Disability Scale (SC-NPAD) and Visual Analog Scale (VAS) for pain assessment, Static Neck Posture Assessment (SNPA) to evaluate neck and shoulder posture and function, Short Form-36 (SF-36) to assess quality of life, and blood tests measuring 5-Hydroxytryptamine (5-HT), Norepinephrine/Noradrenaline (NE/NA), γ-aminobutyric acid (GABA), Adreno-Cortico-Tropic-Hormone (ACTH), ß-Endorphin (ß-EP), and Calcitonin-Gene-Related Peptide (CGRP) levels via high-performance liquid chromatography (HPLC), chemiluminescence immunoassay (CLIA), enzyme-linked immunosorbent assay (ELISA), and radioimmunoassay (RIA). Brain activity changes were monitored through MRI scans. Repeated measures analyses of variance (ANOVAs) will be used to evaluate the outcomes at baseline, at the 12th week, and at the 16th week. Generalized Estimating Equation (GEE) models will be applied to analyze changes in outcomes over time and differences between groups. DISCUSSION: This trial aims to evaluate the efficacy of DT in comparison to other interventions and explore the neuroendocrine mechanisms underlying its effects in adults with CNP. If the intervention and procedures demonstrate feasibility and acceptability, there are plans to conduct a more extensive controlled trial. This could potentially pave the way for the broader application of DT, not only in the context of CNP but also for other chronic diseases. TRIAL REGISTRATION: This trial has been registered with the Chinese Clinical Trial Registry (Registration ID: [ChiCTR2400079571]).

Unexpected early loosening of rectangular straight femoral Zweymüller stems with an alumina-reduced surface after total hip arthroplasty-a prospective, double-blind, randomized controlled trial.

BACKGROUND: Alumina particles from the grit blasting of Ti-alloy stems are suspected to contribute to aseptic loosening. An alumina-reduced stem surface was hypothesized to improve osseointegration and show comparable short-term outcomes to those of a standard stem. METHODS: In this prospective, double-blind, randomized trial, 26 standard (STD) and 27 experimental new technology (NT) stems were implanted. The latter were additionally treated by acid etching and ice blasting to remove alumina particles from the grit-blasting process. Follow-up occurred at 12 and 24 months. Bone mineral density (BMD) around the stem was measured by a dual-energy x-ray absorptiometry device (DEXA). Radiographs were reviewed for alterations. Clinical scoring comprised the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Harris Hip Score (HHS). Survival rates were calculated up to 50 months. RESULTS: Lower mean BMD and more severe cortical hypertrophies were found in the NT group. At 12 months, radiolucent lines were observed mostly in the metaphyseal zone for both groups, with a progression tendency in the NT group at 24 months. At 12 months, pain scores and the WOMAC total and physical activity scores were significantly lower in the NT group, without any differences thereafter. The number of NT stem revisions amounted to 6 (24%) and 11 (41%) at 24 and 50 months, respectively. CONCLUSION: In the NT group, unexpected catastrophic failure rates of 41% caused by early aseptic loosening were noted within 50 months. Compared with the STD stems, NT stems lead to poor clinical and radiographic results. LEVEL OF EVIDENCE: II. TRIAL REGISTRATION: NCT05053048.

Effect and safety of electroacupuncture on weight loss in obese patients with pre-diabetes: study protocol of a randomised controlled trial.

INTRODUCTION: Obesity has been identified as a significant risk factor for several chronic conditions, including diabetes, tumours and cardiovascular disease, and has been associated with increased mortality rates. Despite the well-established clinical practice of electroacupuncture (EA) as a potential treatment option for obesity, its efficacy remains questionable, primarily due to the paucity of empirical evidence supporting its therapeutic benefits. METHODS AND ANALYSIS: The present study aims to investigate the efficacy and safety of EA for weight loss in obese individuals with pre-diabetes, using a randomised, placebo-controlled clinical trial design. A total of 256 eligible patients will be randomly assigned to one of two groups: EA (comprising EA treatment with health education) or superficial acupuncture (SA) (comprising SA treatment with health education). The intervention will be administered three times per week for the initial 12 weeks, two times per week for the subsequent 8 weeks and one time per week for the final 4 weeks, with a 24-week follow-up period. The primary outcome measure will be the percentage of patients who achieve a reduction of 10% or more in their body weight at week 24. Secondary outcome measures will include changes in body weight and body mass index, blood test results, data collected by the body composition analyser, size of adipose tissue scanned by MRI of the abdomen and the Impact of Weight on Quality of Life, the 21-item Three-Factor Eating Questionnaire-Revised and the Food Craving Questionnaire-Trait. The Treatment Emergent Symptom Scale will be employed to monitor every adverse reaction from baseline to follow-up. ETHICS AND DISSEMINATION: This trial has received ethical clearance from the Ethics Committee of Shanghai Municipal Hospital of Traditional Chinese Medicine under the registration number 2021SHL-KY-74. All participants will provide their written informed consent prior to their enrolment. The findings of this investigation will be disseminated through peer-reviewed publications and scholarly conferences. TRIAL REGISTRATION NUMBER: NCT05237089.