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Effects of comprehensive oral care on nasogastric tube removal in long-term care residents with dysphagia: A multi-center randomized controlled trial.

Oral care is essential for residents in long-term care (LTC) facilities to reduce complications such as aspiration pneumonia. While routine oral hygiene is standard practice, comprehensive oral care (COC)-which includes facial and intraoral muscle massage, salivary gland stimulation, and oral moisturization-may further enhance swallowing function. However, evidence linking COC directly to nasogastric (NG) tube removal remains limited. This study evaluated the effectiveness of COC in facilitating NG tube removal and improving swallowing function among LTC residents with dysphagia. A multicenter, open-label randomized controlled trial was conducted across eight LTC facilities. The intervention group (n = 40) received daily one-on-one COC sessions lasting 30-40 min, while the control group (n = 37) received routine oral hygiene. Participants were followed for six months, with outcomes including NG tube removal, swallowing function, body weight, and pneumonia incidence. At six months, the COC group demonstrated a significantly higher NG tube removal rate, with eight participants achieving full oral intake (p = 0.005). Functional Oral Intake Scale scores were also significantly higher in the intervention group (p = 0.005). Time to NG tube removal ranged from 17 to 182 days. Under intention-to-treat principles, the NG tube removal rate remained significantly higher in the COC group (16.7%vs. 0%, p = 0.005). Competing risks analysis using the Aalen-Johansen estimator confirmed a 6-month cumulative incidence of NG tube removal of 14.6% in the COC group versus 0% in the control group (Gray's test: p = 0.005), with no significant between-group difference in mortality (p = 0.500). No significant differences were observed in body weight change or pneumonia incidence between groups. Among participants who successfully discontinued NG tube use, dementia was the most common underlying condition. These findings suggest that daily one-on-one COC is a feasible intervention in LTC settings and may improve swallowing function while facilitating NG tube removal in residents with dysphagia.

Humans

Six weeks of isometric resistance training led to evidence of corticospinal but not reticulospinal adaptation in previously untrained adult males.

The latest hypothesis regarding the source of enhanced neural activation from resistance training is the reticulospinal rather than the corticospinal tract, based on invasive animal and emerging human data. The present study employed a six-week isometric resistance training intervention in a randomized controlled design to address this knowledge gap. Thirty-nine healthy, untrained males (age ~23 y, sustained contraction group n = 13, explosive contraction group n = 9, control group n = 17) underwent neuromuscular and electrophysiological testing and completed all study requirements. Maximal isometric torque (MVC) and rate of torque development (RTD) were measured during a familiarization session as well as before and after the six-week period. Transcranial magnetic stimulation was used to assess motor-evoked potential (MEP) area and silent period duration while subjects contracted to 10% of MVC. Loud sound (120&#xa0;dB) was used to modulate MEP area and reaction time to visual stimuli during the StartReact test. Only the intervention groups demonstrated significant improvements in MVC (27%) and RTD (60%) (both P < 0.01), along with reduced MEP area (-&#xa0;21%) and silent period duration (-&#xa0;23%) (both P < 0.01). The sustained contraction group showed reduced modulation of reaction time and increased MEP suppression due to loud sound. Short-term resistance training seemed to reduce cortical inhibition and corticospinal excitability in both training groups. The study showed conflicting changes in measures purported to evaluate reticulospinal functioning. It is recommended to examine different forms of resistance training and longer training exposure in future.

Humans

Effects of testosterone-augmented multimodal exercise intervention in spinal cord injury: a randomized controlled trial.

CONTEXT: Spinal cord injury (SCI) leads to profound muscle atrophy, aerobic deconditioning, and metabolic dysfunction. Exercise-based interventions alone produce modest benefits. Whether testosterone can augment physiologic responses to exercise in this population remains untested. OBJECTIVE: To evaluate efficacy and safety of home-based intervention combining functional electrical stimulation-assisted leg cycling (FES-LC), arm ergometry (AE), and testosterone compared with FES-LC, AE plus placebo in adults with SCI. METHODS: This randomized, placebo-controlled, double-blind trial enrolled 84 adults (76 males and 8 females) aged 19-70 years with SCI (neurologic levels C4-T12; AIS grades A-D). Participants were randomized to multimodality intervention (home-based FES-LC, AE and intramuscular testosterone undecanoate) (n = 38) or control intervention (FES-LC, AE plus placebo) (n = 46) for 16 weeks. The primary outcome was change in aerobic capacity (peak VO2) during AE cardiopulmonary exercise testing. Secondary outcomes included lean mass, hemoglobin, cardiometabolic markers, and safety. RESULTS: Mean (SD) age was 44 (13) years and time since injury was 13.9 (13) years). Between-group changes in peak VO2 were not statistically significant. Within-group improvements were larger in multimodality (&#x223c;19% increase; 0.10 L/min; 95% CI, 0.02-0.18 L/min) compared to controls (&#x223c;6% increase; 0.06 L/min; 95% CI, -0.01-0.13). The multimodality group gained significantly more lean mass (whole-body:1.84 kg, 95% CI: 0.52-3.16, P = .007; lower extremity 0.92 kg, 95% CI: 0.38-1.45, P = .001), and anemia was corrected in a greater proportion of participants. Adverse event rates were similar between groups. CONCLUSION: A home-based multimodality intervention combining FES-LC, AE, and testosterone was safe and associated with greater improvements in lean mass and hemoglobin. Although between-group differences in aerobic capacity were not statistically significant, greater within-group increases were observed in the multimodality group. These findings may inform future studies of testosterone-augmented exercise interventions for individuals living with SCI.

Humans

Proteomic and phosphoproteomic profiles of time-dependent dynamic changes in LPS-induced macrophage polarization.

The temporal proteomic and phosphoproteomic reprogramming during early M1 macrophage polarization (0-6&#xa0;h) remains poorly understood. We performed time-resolved proteomic and phosphoproteomic analyses of LPS-stimulated RAW264.7 macrophages at seven time points within 6&#xa0;h. Time-clustering of differentially expressed molecules revealed two patterns: initial change with partial recovery, and sustained dysregulation. Upregulated proteins and phosphorylation sites were enriched in the Rho GTPase signaling pathway, T-cell receptor signaling pathway, NF-&#x3ba;B cascade, osteoclast differentiation pathway, and antiviral immune pathway. Downregulated pathways were associated with cell cycle regulation, chromatin remodeling, RNA metabolism, and mRNA processing, indicating resource reallocation to prioritize acute inflammatory responses. Kinase-substrate network analysis confirmed the mitogen-activated protein kinase (MAPK), cyclin-dependent kinase (CDK), protein kinase B (AKT), and ribosomal S6 kinase (RSK) families as core upstream phosphorylation regulators. Integrated analysis revealed synergistic and antagonistic relationships between proteomic and phosphoproteomic changes. This study provides a temporal molecular atlas of M1 polarization, delineating inflammatory signaling dynamics and offering a basis for therapeutic target discovery in inflammatory diseases. SIGNIFICANCE: Macrophage M1 polarization is a central event in innate immune defense against pathogenic invasion, yet its dysregulation is a pivotal driver of the onset and progression of a broad spectrum of inflammation-associated disorders, spanning autoimmune diseases, infectious conditions and inflammatory bone diseases, making the dissection of its molecular regulatory mechanisms an urgent research priority in immunology and translational medicine. Dynamic molecular events within 0-6&#xa0;h after LPS stimulation are critical for initiating and shaping M1 inflammatory activation, yet systematic time-resolved proteomic and phosphoproteomic profiling remains insufficient.In this study, we comprehensively characterized temporal proteome and phosphoproteome changes at seven consecutive time points during macrophage polarization, clarified two distinct dynamic molecular patterns, identified core signaling pathways and key kinase regulators involved in inflammatory reprogramming, and uncovered the leading role of post-translational phosphorylation modifications in initiating polarization. This work delineates the time-series molecular atlas of early macrophage activation, provides novel insights into the temporal regulatory mechanism of inflammatory signaling networks, and lays a solid experimental foundation for exploring new intervention targets and regulatory nodes in clinical translational research.

Lipopolysaccharides

Effects of cinnamon supplementation combined with exercise training on anthropometric indices and reproductive hormones in overweight and obese women.

BACKGROUND: The prevalence of obesity and increased fat in the chest and abdomen in women and hormonal changes, can affect female fertility. The present study aims to investigate the effect of exercise training combined with cinnamon supplementation on chest and abdominal circumference, as well as sex hormones, in overweight and obese women. METHODS: Twenty-six inactive overweight and obese women were randomly allocated to an exercise (E; n = 13) and exercise plus cinnamon supplementation (E+S; n = 13) group. Both groups completed a 4-week exercise program three times weekly, while the E+S group additionally received cinnamon supplementation three times weekly. Chest and abdominal circumferences and serum concentrations of estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were assessed before and after the intervention. RESULTS: Significant pre-to-post reductions in chest and abdominal circumference were observed in both groups (all p &#x2264; 0.005). Estradiol, progesterone, and FSH concentrations increased, whereas LH concentrations decreased significantly in both groups (all p &#x2264; 0.005). However, between-group comparisons revealed a significant difference only for chest circumference (p = 0.003), with no significant group differences in abdominal circumference or any reproductive hormone concentration (all p > 0.05). CONCLUSION: Both groups showed favorable changes in anthropometric and reproductive hormone measures following the 4-week study period. However, the significant between-group difference was limited to chest circumference, providing no clear evidence that cinnamon supplementation conferred additional benefits for abdominal circumference or reproductive hormone profiles beyond those observed with exercise. These findings highlight the potential relevance of exercise-based interventions while warranting confirmation in larger, adequately powered trials.

Humans

Faster N1 latency in response to homeostatic-like plasticity of PREPs is impaired during pain: A randomized-placebo capsaicin-pain study.

INTRODUCTION: Homeostatic-like plasticity (HP-like) stabilizes cortical excitability through long-term potentiation and depression-like mechanisms. The efficacy of homeostatic regulation in the corticomotor system is impaired during pain, which may have functional relevance for chronic pain. This study investigated whether a cortical HP-like response could be assessed by nociceptive stimulation, and if such response was impaired by experimental tonic pain. METHODS: Twenty-eight healthy participants completed placebo and capsaicin sessions, with 11 sham controls for time and design. HP-like plasticity was induced with two blocks of anodal tDCS over the primary motor cortex. The N1 (TP7) and N2P2 (Cz) components of electrically induced pain-related evoked potentials (PREPs) were assessed from the volar forearm before and after patch application, and again immediately and 20&#xa0;min after HP-like induction. An HP-like response was defined by PREP decrease after induction, and further normalization to baseline. RESULTS: Anodal tDCS did not induce an HP-like regulation of PREP amplitudes. Interestingly, an HP-like response was observed as a fastening of N1 latency after HP-like induction, which returned to baseline values after 20&#xa0;min. The latter effect was impaired during capsaicin-induced pain, where N1 was slower. The N2P2 component showed habituation over time in all sessions. CONCLUSION: This is the first study that investigates the HP-like regulation of nociceptive-evoked responses. An HP-like response was observed as a shortening of N1 latency, suggesting that early nociceptive processing may be susceptible to homeostatic regulation. In contrast, the later component, N2P2, showed habituation over time, which prevented evaluation of HP-like effects.

Humans

Outcomes of patients with myelofibrosis treated with ruxolitinib and anemia-supporting medications.

OBJECTIVE: This post hoc analysis of the phase 3b JUMP trial evaluated addition of anemia-supporting medications to ruxolitinib in patients with myelofibrosis and anemia. METHODS: 101 patients with baseline hemoglobin <12.0&#x2009;g/dL initiated an erythropoiesis-stimulating agent (ESA) or danazol <3&#x2009;months post-enrollment and maintained ESA/danazol &#x2265;3&#x2009;months; 97% initiated ESAs. Patients enrolled in JUMP who had hemoglobin <12.0&#x2009;g/dL but did not initiate ESAs/danazol within 3 months were evaluated as an unmatched comparator. Total JUMP population data were also analyzed for spleen length (&#x2265;50% reduction from baseline) and symptom response (&#x2265;6.5-point improvement in FACT-Lym score). RESULTS: Baseline characteristics were similar to comparator JUMP patients (no ESAs/danazol within 3&#x2009;months, n&#x2009;=&#x2009;1242). Mean total daily ruxolitinib dose remained >25&#x2009;mg. Week 24 spleen length response was achieved by 37% of patients; 26% achieved symptom response, similar to the comparator population (28% and 26%, respectively) and comparable to the total JUMP population (N&#x2009;=&#x2009;2233). Outcomes were similar between the hemoglobin <12.0&#x2009;g/dL analysis population and patients with baseline hemoglobin <10.0&#x2009;g/dL (n&#x2009;=&#x2009;52). In all groups, hemoglobin levels increased after Week 4 following an expected initial decrease. DISCUSSION: This analysis suggests that patients treated with ruxolitinib and anemia-supporting care continued to receive optimal ruxolitinib dosing; spleen-length and symptom response rates in these patients were comparable to the overall JUMP population, the majority of whom did not have anemia. CONCLUSION: Results support use of anemia-supporting medications with ruxolitinib and may allow maintenance of ruxolitinib dose intensity in patients with myelofibrosis and anemia.

Humans

Efficacy of targeted neuromodulation treatments: a clinical report.

BACKGROUND: Peripheral neuropathy is a debilitating condition characterized by chronic pain, numbness, tingling, burning, and tightness/swelling. Conventional therapies often focus on symptom management, and some patients experience chronic and refractory symptoms. RESEARCH DESIGN AND METHODS: This retrospective clinical analysis evaluated the clinical outcomes of neuromodulation neuropathy treatment using the NeuroGen-Series device in patients with diabetic peripheral neuropathy (DPN) or idiopathic peripheral neuropathy (IPN). 9,805 unique patients who underwent 133,741 treatments between 18 August 2017, and 23 July 2024, were analyzed. Patients were divided into treatment completers (&#x2265;24 sessions) and noncompleters (<24 sessions). Paired t-tests confirmed statistically significant reductions in pre- and post-treatment symptom scores (p&#x2009;<&#x2009;0.001). RESULTS: Among completers, symptom severity decreased by an average of 46.2%. Tingling and pain showed the greatest improvement, while tightness/swelling and numbness showed the least reduction. 64% of patients reported improvement after one session, and 84% reported improvement after 24 sessions. Nonresponders accounted for 5.8% of patients overall. Younger patients and those with higher initial symptom severity were more likely to discontinue treatment. CONCLUSIONS: Overall, neuromodulation treatment resulted in statistically significant reductions in symptom severity, though nonresponders and high attrition rate highlight the need for individualized treatment strategies and further investigation.

Humans

Associations between prescribed amphetamines and spontaneous cervical artery dissection: a matched case-control study.

AIMS: To assess whether prescribed amphetamines are associated with spontaneous cervical artery dissection (sCeAD), an important cause of stroke in young adults. METHODS: We conducted a retrospective matched case-control study within a large academic health system in Chicago, Illinois. Adults aged 18-85&#xa0;years with incident sCeAD were matched 1:4 to controls without dissection on age, sex, and race/ethnicity. The primary exposure was documented amphetamine prescription. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) controlling for relevant vascular and clinical covariates. Sensitivity analyses included strict matched-strata and inverse probability-weighted models. RESULTS: Among 11,463 individuals, including 2,293 cases and 9,170 controls, amphetamine exposure was associated with higher odds of sCeAD (adjusted OR 1.70, 95% CI 1.18-2.46). Results were unchanged in strictly matched strata (OR 1.70, 95% CI 1.18-2.46) and remained directionally consistent after inverse probability weighting (OR 1.40, 95% CI 1.09-1.79). High-dose amphetamine exposure (&#x2265;30&#xa0;mg/day) had the strongest association (OR 1.96, 95% CI 1.18-3.26), whereas low-dose exposure was not statistically significant. CONCLUSION: Prescribed amphetamines were associated with modestly increased odds of sCeAD. While these findings are observational and hypothesis-generating, they may support a possible association in susceptible patients.

Humans

Predictive value of anal sphincter electromyography for sacral neuromodulation test-phase outcomes.

BACKGROUND: Sacral neuromodulation (SNM) is an established therapy for refractory pelvic organ dysfunction. Anal sphincter electromyography (EMG) is commonly used preoperatively to assess sacral and peripheral nerve integrity. However, the prognostic significance of chronic neurogenic EMG changes for SNM outcomes remains unclear. OBJECTIVE: To evaluate whether chronic neurogenic changes on preoperative anal sphincter EMG predict the outcome of the SNM test phase. METHODS: We retrospectively analysed 62 consecutive patients with bladder and/or bowel dysfunction or pelvic pain who were candidates for SNM treatment and who underwent preoperative anal sphincter EMG. EMG findings were classified as normal or showing chronic neurogenic changes. SNM test-phase success was defined as a &#x2265;50% improvement of symptoms at 24&#xa0;days. Outcomes were compared between EMG groups. RESULTS: Of the 62 patients (49 women, 13 men), 30 (48%) had normal EMG findings and 32 (52%) showed chronic neurogenic changes. Overall, the SNM test phase was successful in 47 patients (76%). Success rates were similar in patients with normal EMG (72%) and neurogenic EMG changes (79%), with no statistically significant difference (p&#xa0;=&#xa0;0.878). Sex-stratified analyses revealed no significant association between EMG findings and test-phase success in women or men. CONCLUSIONS: Chronic neurogenic changes on anal sphincter EMG do not predict SNM test-phase outcomes. These findings suggest that abnormal sphincter EMG results should not be used as a standalone criterion to exclude patients from SNM therapy. SIGNIFICANCE: Signs of neurogenic damage on anal sphincter EMG are not an indicator of reduced neuromodulatory capacity or diminished clinical response to SNM.

Humans

The effect of olfactory training and odor exposure on visual selective attention.

Olfactory training (OT) is a well-established, non-invasive intervention that improves olfactory function by repeated, structured exposure to odorants. Beyond sensory outcomes, it also influences multiple aspects of cognition. Yet, its influence on attention, a fundamental process underlying many cognitive domains, remains unclear. This study examined the impact of a 12-week OT program on visual selective attentional performance and the effect of on-task odor exposure. Ninety-four healthy participants were initially included, and randomized into OT or placebo groups. Participants completed the d2 Test of Attention simultaneously with and without odor exposure in a randomized sequence at baseline, post-training, and a follow-up four weeks after stopping the training. The d2 test measures commission errors, omission errors, and concentration performance. Ninety-three participants (OT=51, placebo=42) completed baseline measurement, 74 (OT=39, placebo=35) returned for post-training session, and 57 participants (OT=29, placebo=28) returned for the follow-up appointment. Results showed that OT did not significantly improve d2 test performance. In the primary model, on-task PEA exposure reduced commission errors compared to the odorless condition, suggesting a possible transient effect of olfactory input on the inhibitory control in the context of the d2 attentional test. This effect, however, was no longer significant once the follow-up data were included and should be regarded as preliminary. Overall, these findings raise the possibility of a distinction between relatively long-term OT and short-term odor exposure: while OT did not improve visual selective attention, brief on-task odor exposure may transiently enhance inhibitory control during attentional tasks, a possibility that remains to be confirmed.

Humans

Gonadal function and fertility outcomes after orchiopexy versus orchiectomy for testicular torsion: A systematic review and meta-analysis.

PURPOSE: To review the early and late changes in hormonal profiles, semen parameters, and clinical outcomes in patients treated with orchiopexy versus orchiectomy for testicular torsion. METHODS: A systematic search was conducted across MEDLINE, Scopus, Web of Science, Cochrane Library, and other databases, following PRISMA guidelines. PRIMARY OUTCOMES: FSH, LH, testosterone, inhibin-B, and semen parameters. Quality was assessed using the Newcastle-Ottawa Scale. Certainty of evidence was evaluated using the GRADE framework. Statistical analysis was performed using the random-effects model. RESULTS: Eleven studies involving 538 participants (197 orchiectomy, 341 orchiopexy) were included. Orchiectomy was associated with a significant increase in FSH (SMD: 1.63, P < 0.0001) and LH (SMD: 1.31, P < 0.0001) compared to orchiopexy. However, testosterone (MD: 0.31 ng/mL; P = 0.4) and inhibin-B (SMD: -0.14; P = 0.87) levels were comparable between groups. Regarding semen parameters, orchiectomy resulted in a significant reduction in sperm concentration (MD: -18 million/mL, P = 0.01). No significant differences were found in sperm count (MD: 13.9 million; P = 0.43), normal morphology (MD: 4.97%; P = 0.12), or total motility (MD: 4.05%; P = 0.49). The pooled rate for ipsilateral atrophy following orchiopexy was 38%, which likely depends on ischemia duration. CONCLUSION: Surgical choice in testicular torsion does not significantly affect the overall hormonal balance or most semen parameters due to compensatory mechanisms of the hypothalamic-pituitary-gonadal axis. Clinical decisions should consider individual case factors, as we lack reliable data on subsequent paternity rates.

Male

The Effectiveness of Passive Half-Time Interventions on Simulated Second-Half Performance in Elite Youth Soccer Players.

The half-time period in soccer provides a potentially important window to implement short-duration interventions aimed at maintaining second-half performance. However, passive rest has been associated with a decline in subsequent physical and technical performance. While re-warm-up strategies are well studied, little is known about the efficacy of technology-based, passive recovery modalities, device-supported interventions that require minimal active movement or physical exertion from the athlete, during half-time intervals. This study examined whether percussive therapy, electrical muscle stimulation, and pneumatic compression can mitigate second-half performance decline in male adolescent soccer players. Forty-three academy-level players (17.5 &#xb1; 0.6 years) completed a simulated soccer protocol including the Loughborough Soccer Pass Test (LSPT), repeated 20-meter sprints, and completed Total Quality of Recovery (TQR) assessments before and after half-time. Participants were randomized into one of four intervention groups during the 15-minute half-time interval: Passive Rest (CON), Percussive Therapy (Theragun Pro; TG), EMS (PowerDot; PD), and Pneumatic Compression (RecoveryAir; COMP). Linear mixed-effects models assessed Time &#xd7; Condition interactions for performance and recovery outcomes. Passive half-time rest led to significant deterioration in technical skill, sprint performance, and perceived recovery (p < .05) for the control group. TG and PD significantly improved technical performance (LSPT scores) compared to the control group (d = 0.65 and 0.72, respectively; p < .01). Furthermore, TG and COMP were effective at maintaining 20-meter sprint times (d = 0.58 and 0.49; p < .01), whereas the control group experienced significant slowing. Perceived recovery (TQR) scores significantly declined in the CON group from First Half to Second Half (16.5 &#xb1; 2.2 to 11.1 &#xb1; 2.3. However, this decline was significantly attenuated in all intervention groups: TG (17.5 &#xb1; 1.9 to 14.2 &#xb1; 1.9), PD (17.3 &#xb1; 1.9 to 15.1 &#xb1; 1.9), and COMP (17.6 &#xb1; 1.9 to 15.9 &#xb1; 2.0). Short-duration passive interventions during half-time can mitigate performance decline in adolescent soccer players. TG and EMS appear most effective for preserving technical skills, while COMP may support perceived recovery. These findings highlight practical strategies for optimizing in-game performance and inform evidence-based half-time protocols.

Humans

Muscle Massage Adding Capacitive Resistive Electric Transfer Therapy in Active or Sham Condition for Post-Exercise Recovery in Athletes: A Crossover Clinical Trial.

The increasing demands of elite sports reduce recovery time, impair performance, and increase injury risk. Efficient lactate transport is essential for postexercise recovery. Capacitive resistive electric transfer (CRET) therapy enhances deep tissue heating, induces vasodilation, and promotes circulation. To evaluate whether adding active CRET to a standardized muscle recovery massage, compared with the same massage plus sham CRET, influences indicators of muscle recovery following a maximal anaerobic effort test. A randomized, single-blind, sham-controlled, and crossover clinical trial was conducted in 25 athletes. Participants completed four visits and, after the maximal power and anaerobic capacity test (Wingate test), received a standardized muscle recovery massage combined with either active CRET or sham CRET. Blood lactate levels, muscle oxygenation, muscle thickness, echogenicity, knee extension force, and muscle activity were assessed before and after the test, after treatment, and 24&#xa0;hours later. Compared with massage plus sham CRET, massage plus active CRET was associated with lower blood lactate concentration at 60&#xa0;min postexercise (p&#xa0;=&#xa0;0.029). Ultrasound-derived muscle thickness and echogenicity also differed between conditions at several time points (p&#xa0;<&#xa0;0.05). However, no significant differences were observed in Wingate test performance, force, muscle activity, and oxygenation between conditions. In athletes performing repeated Wingate exercise, adding active CRET to massage was associated with lower blood lactate concentration at 60&#xa0;min postexercise and with differences in ultrasound-derived muscle thickness and echogenicity compared with sham CRET plus massage. However, these between-condition differences were not accompanied by clear short-term functional recovery benefits. TRIAL REGISTRATION: NCT06906146.

Humans

[Exploring the mechanism underlying the efficacy differences of "Tiaojing Cuyun Acupuncture"for premature ovarian failure based on vaginal microbiota structure].

OBJECTIVE: To observe the efficacy of "Tiaojing Cuyun Acupuncture" combined with hormone replacement therapy in the treatment of premature ovarian failure (POF), and to investigate differences in vaginal microbiota among patients with different therapeutic responses, thereby preliminarily exploring the mechanism underlying efficacy differences. METHODS: Ninety-eight patients with POF were randomly divided into an observation group (49 cases, 1 case was eliminated)and a control group (49 cases, 1 case dropped out). The control group was treated with hormone replacement therapy with Femoston, one tablet each time, once daily. On the basis of the control group, the observation group was additionally treated with "Tiaojing Cuyun Acupuncture". Acupoint group 1 included Baihui (GV20), Zhongwan (CV12), Guanyuan (CV4), and bilateral Tianshu (ST25), Zigong (EX-CA1), Dahe (KI12), Zusanli (ST36), Sanyinjiao (SP6), and Taichong (LR3). Acupoint group 2 included Baihui (GV20), bilateral Shenshu (BL23), Ciliao (BL32), and Taixi (KI3). The two acupoint groups were used alternately, beginning with acupoint group 1. Treatment was administered once every other day, three times per week.Both groups were treated for three menstrual cycles. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH),estradiol (E2), and anti-M &#xfc; llerian hormone (AMH) levels on days 3-5 of the menstrual cycle were measured before and after treatment in the two groups. Self-rating anxiety scale (SAS) scores were assessed before and after treatment, and clinical efficacy was evaluated in the two groups. Five effective patients (G0 subgroup) and five ineffective patients (G1 subgroup)were randomly selected from each group, and their vaginal microbiota structure was analyzed using 16S rRNA sequencing. RESULTS: After treatment, FSH levels in both groups were lower than those before treatment (P<0.05); SAS scores in both groups were lower than those before treatment (P<0.05), and the observation group had lower SAS score than the control group (P<0.05). The total effective rate was 77.1% (37/48) in the observation group, which was higher than 56.3% (27/48) in the control group (P<0.05). Vaginal microbiota analysis showed that at the phylum level, the relative abundance of Firmicutes in the G0 subgroup of the control group was higher than that in the G1 subgroup, while the relative abundances of Bacteroidetes, Actinobacteria and Proteobacteria were lowed in the G0 subgroup. In contrast, the observation group exhibited an opposite trend: the G0 subgroup had lower Firmicutes abundance but higher abundances of Actinobacteria, Bacteroidetes and Proteobacteria compared with the G1 subgroup. At the family and genus levels, Bifidobacterium was enriched in the G0 subgroups of both groups, whereas Lactobacillus predominated in the G1 subgroups. The G0 subgroup of the control group showed higher abundance of Gardnerella, while both Lactobacillus and Gardnerella were concurrently elevated in the G1 subgroup of the observation group. Additionally, in the observation group indicated that Clostridiales and Rikenellaceae were significantly more abundant in the G0 subgroup than in the G1 subgroup (P<0.05). CONCLUSION: The "Tiaojing Cuyun Acupuncture" combined with hormone replacement therapy is superior to hormone replacement therapy alone in improving anxiety. There are differences in vaginal microbiota structure among patients with different theraputic efficacy, suggesting that the vaginal microecological environment may be involved in the mechanism of treatment response in POF.

Humans

Evaluation of pilocarpine effects on sweat proteome.

BACKGROUND: Sweat is increasingly recognized as a valuable, non-invasive biofluid for biomarker discovery, yet its composition depends on the stimulation method. This study aimed to determine how pharmacological induction with pilocarpine compares to physiologically induced sweat through exercise in shaping the sweat proteome. RESULTS: We analyzed thermoregulatory sweat from exercise, pilocarpine-induced sweat, and combined pilocarpine plus exercise sweat. Total protein concentrations were similar across conditions, but pilocarpine markedly increased proteomic diversity, with combined pilocarpine plus exercise sweat showing the highest number of identifications. The core sweat proteome remained stable, while pilocarpine selectively enriched low-abundance proteins involved in vesicular trafficking, cytoskeletal remodelling, and metabolism. Proteins linked to the canonical M3-Gq-PLC-Ca2+ pathway, including AQP5, CALML5, and CLIC1, were consistently enriched, confirming cholinergic activation. Pilocarpine-induced sweat also contained plasma-derived and immune-related proteins, reflecting enhanced secretion and reduced ductal reabsorption. CONCLUSIONS: Exercise yields a physiologically relevant but less complex proteome, pilocarpine-induced sweat produces a pharmacologically enriched yet biased profile, and combined pilocarpine plus exercise sweat maximizes protein detection at the expense of interpretability. These findings highlight the critical impact of stimulation paradigm on sweat proteomics and provide a reference framework for biomarker research. SIGNIFICANCE: This study employed LC-MS/MS to systematically characterize eccrine sweat and delineate how stimulation paradigms-exercise, pilocarpine, and their combination-shape its proteomic landscape. By demonstrating that pharmacological induction profoundly alters protein diversity and composition compared to physiologically induced sweat, these findings establish a critical benchmark for sweat-based biomarker research and highlight the need for paradigm-aware sampling strategies in clinical and translational contexts. Nonetheless, several methodological constraints warrant consideration: the limited sample size (five individuals per group), the exclusive inclusion of women under combined oral contraceptive treatment (21 active pills followed by 7 pill-free days), which restricts extrapolation to naturally cycling women, and the focus on healthy young adults (18-25&#xa0;years), limiting generalizability to older or clinically heterogeneous populations. Despite these limitations, this work provides a foundational framework for optimizing sweat collection protocols and advancing precision approaches in non-invasive diagnostics.

Pilocarpine

Multi-centre randomised controlled feasibility trial with embedded process evaluation of a samba percussion intervention for people living with Parkinson's disease: a protocol for the Sparky Samba trial.

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder, its principal symptom being deterioration of motor function. Current treatment options are limited to symptom management but there is evidence that physical activity can provide motor benefits. More recently there is evidence to suggest that rhythmic auditory stimulation may improve gait and balance in PD. Sparky Samba is a community initiative in South Wales, UK, founded by a person living with PD. Sessions incorporate the following samba rhythms from a trained facilitator and are held weekly in a community setting. METHODS: The Sparky Samba trial is a multi-site, non-blinded, randomised controlled feasibility trial of Sparky Samba compared with activity as usual. A total of 60 people with PD will be randomised 1:1 to take part in a local Sparky Samba group for 12 weeks or continue their normal activities for the same length of time. The primary outcome is feasibility defined by recruitment, retention, data completeness and intervention adherence. Secondary outcomes relating to motor function, cognition, well-being and self-efficacy will also be assessed at baseline and at 12 weeks. Additionally, we will conduct a process evaluation to understand contextual mechanisms surrounding Sparky Samba. This will be achieved through qualitative interviews and structured participant questionnaires following individual trial completion and through structured questionnaires with intervention delivery staff, supplemented with qualitative interviews. ANALYSIS: Feasibility outcomes will be assessed according to pre-defined criteria. For secondary outcomes, means and standard deviations (or medians and IQRs) will be calculated by arm, alongside 95% CIs for change from baseline to 12-week follow-up. Qualitative data will be subject to thematic analysis using NVivo software. ETHICS AND DISSEMINATION: This study received a favourable ethical opinion from the North of Scotland Research Ethics Committee in April 2025 (REC reference 25/NS/0037). Study results will be disseminated through the peer-review literature, the ISRCTN registry and directly to participants, which will be facilitated by the study's public and patient involvement steering group. TRIAL REGISTRATION NUMBER: ISRCTN11861663.

Humans

Identification of CD55 as a downstream factor of EP4 receptor signaling in colorectal cancer cells.

Prostaglandin E2 (PGE2) signaling through the E-type prostanoid 4 (EP4) receptor has been implicated in the pathophysiology of colorectal cancer (CRC). We herein identified decay-accelerating factor, also known as CD55, as a novel CRC-associated downstream factor of the EP4 receptor. The integration of transcriptomic profiling of PGE2-stimulated HCA-7 human colon cancer cells with analyses of cancer genomic databases predicted CD55 as a potential EP4 receptor-regulated target. Inhibitor-based experiments showed the induction of CD55 after a PGE2 stimulation required the EP4 receptor and Gi protein in HCA-7 cells, whereas protein kinase A signaling was dispensable. In combination with a toxicogenomic database analysis, p38 mitogen-activated protein kinase (MAPK) was identified as the predominant effector connecting the EP4 receptor to CD55 upregulation. A single-cell RNA-seq re-analysis of human CRC tissues revealed CD55 upregulation and p38 MAPK-related gene set enrichment in epithelial cells expressing the EP4 receptor, suggesting that this induction mechanism may operate in a subset of epithelial cells in clinical specimens. Collectively, these results delineate a PGE2/EP4 receptor/Gi protein/p38 MAPK signaling axis that induces CD55 expression in HCA-7 cells and epithelial tumor cells, provide new mechanistic clues for understanding the regulation of complement regulatory molecule CD55 expression by prostaglandin signaling.

Humans