Due to nusinersen’s route of administration and dosing regimen, the spinal muscular atrophy (SMA) population and/or their caregivers need to travel to hospitals and work around physician’s schedules to receive treatment. Real-world studies with large sample sizes on administration practice and adherence rate of nusinersen are lacking, especially in non-United States settings. This study aimed to investigate the administration practice and adherence of nusinersen in Chinese adults with 5q-SMA. An ambispective, multicenter registry of adults with 5q-SMA in China provided the longitudinal data for this analysis. Nusinersen was scheduled on Day 0, 14, 28, 63, and every 4 months thereafter. Adherence rate was calculated at dose level. A dose was deemed adherent if the interval between the current and preceding dose aligned with the standard dosing regimen, allowing a grace period of ± 7 days for doses 2 through 4 and ± 28 days for all subsequent doses. A total of 177 participants receiving nusinersen with 1,329 doses were included in the study. All injections were given in inpatient setting with no ventilatory support or sedation needed. Only one injection (0.1

Currently, no curative therapies exist for Amyotrophic Lateral Sclerosis (ALS). This study aimed to evaluate the efficacy and safety of Huoling Shengji granules (HLSJ), a traditional Chinese medicine (TCM), compared to the standard treatment riluzole. A multicenter, randomized, double-blind, double-dummy, active-controlled Phase II clinical trial was conducted across 11 centers in China. A total of 140 ALS patients were randomly assigned (1:1) to receive either HLSJ or riluzole for 48 weeks. The primary endpoint, analyzed in the full analysis set (FAS), was the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score from baseline to Week 48. Safety profiles were comparable between groups, with no significant difference in adverse events (80.28% vs. 80.56%, P = 0.9671). Analysis using the pre-specified Last Observation Carried Forward (LOCF) method showed a numerical advantage for HLSJ (1.07 points) but lacked statistical superiority. However, a more scientific analysis using the Mixed Model for Repeated Measures (MMRM), recommended for progressive diseases, indicated that HLSJ was significantly superior to riluzole in slowing ALSFRS-R score decline (Least Squares Mean Difference [LSMD]: 2.29 points; 95% confidence interval [CI]: 0.52 to 4.06; P = 0.0114). While the LOCF model showed no statistical difference, the MMRM analysis confirmed that HLSJ demonstrated significant efficacy superior to riluzole with a favorable safety profile. These findings provide a critical basis for conducting pivotal Phase III confirmatory trials of HLSJ for ALS treatment.

Introduction: As a rare neurodegenerative disease, the prognosis of Amyotrophic lateral sclerosis (ALS) is closely linked to motor symptoms. Recent research has increasingly concentrated on non-motor symptoms (NMS), especially constipation, and their correlation with survival in patients with ALS. However, it is unclear whether there is an interaction and/or mediation effect between NMS, especially constipation, and ALS progression and survival. Therefore, this study aims to investigate the role of NMS in the relationship between ALS progression and survival. Methods: We conducted a multicenter prospective cohort study on ALS patients. Based on the inclusion and exclusion diagnoses, we collected a total of 150 ALS patients and conducted a nine-month follow-up. Results: We applied the VanderWeele's Four-Way Decomposition method to decompose the excess risk of moderate (ΔFS: 0.47-1.1/month)/fast (ΔFS>1.1/month) ALS progression compared to slow (ΔFS<0.47/month) ALS progression into four components. The results indicated that the interaction effect between constipation and the progression rate of ALS (moderate/severe) played a significant role, with values of 2.571 and 10.819, accounting for 81.890% and 91.590% of the total increased excess risk, respectively (P<0.05). Conclusions: Our results suggest that constipation plays an interaction role between ALS progression and survival. Clinical Trial Registration number: ChiCTR2500101119. The registration time is 21/04/2025.

BACKGROUND:Hyaluronic acid (HA) is a cornerstone of aesthetic skin treatments due to its vital role in skin hydration and combating aging signs. OBJECTIVE:This trial evaluated the efficacy and safety of a novel non-cross-linked HA gel for improving skin quality in a Chinese population. MATERIALS AND METHODS:In this multicenter, randomized, controlled trial, 420 subjects were enrolled (2:1, treatment: control). The treatment group received three full-face intradermal injections of the HA gel at 3-week intervals, whereas the control group received no intervention. Primary end points were blinded evaluations of the Global Aesthetic Improvement Scale and a composite improvement rate for skin dryness/dullness. RESULTS:The treatment group showed significantly higher Global Aesthetic Improvement Scale improvement (90.63% vs 3.65%) and composite improvement rates (83.20% vs 3.65%) than control group ( p < .0001), with effects sustained for 6 months. Skin hydration and elasticity significantly increased from baseline ( p < .05). Peak efficacy rates for fine lines and roughness reached 51.59% and 50.00%, respectively. Adverse events were mild and transient, with decreasing incidence. CONCLUSION:This non-cross-linked HA gel effectively enhances skin hydration, elasticity, and texture with sustained 6-month benefits and a favorable safety profile, supporting its use for facial rejuvenation.

The diagnosis of amyotrophic lateral sclerosis (ALS) mainly relies on clinical symptoms and the exclusion of other diseases, with a lack of specific biomarkers, leading to delayed diagnosis and a high rate of misdiagnosis. This study aims to explore the utility of peripheral immune cells and glycosylation indices as potential diagnostic biomarkers for ALS to enhance the accuracy and efficiency of early ALS diagnosis. This retrospective study included 54 ALS patients diagnosed in our hospital from June 2023 to October 2024, along with 54 healthy controls. Blood samples and laboratory data, including levels of peripheral immune cells and glycosylation indices, were collected from both groups. Through logistic regression, random forest models, receiver operating characteristic (ROC) curve analysis, and SHAP interpretability analysis, the predictive abilities and clinical significance of each candidate indicator were screened and evaluated. Notable disparities were detected in age, leukocyte count, monocyte levels, glycated haemoglobin A1c (HbA1c), and haemoglobin glycation index (HGI) between the control and ALS groups (all P < 0.05). Logistic regression analysis revealed that age (OR = 1.114) and monocyte (OR = 3.174) were risk factors for ALS, while leukocyte (OR = 0.533) and HbA1c (OR = 0.069) were protective factors. The random forest algorithm, ranked by decreasing importance, showed that leukocyte, HGI, monocyte, and HbA1c level all influenced ALS. Using these indicators to predict ALS resulted in a false-positive rate of 18% and a false-negative rate of 6%. ROC curve analysis indicated that the combined use of leukocyte, monocyte, HbA1c level, and HGI provided the highest diagnostic value for ALS (AUC = 0.774), which was higher than that of any individual indicator (all P < 0.05). SHAP analysis visualization demonstrated that increased monocyte and decreased leukocyte, HGI, and HbA1c level were all associated with an increased risk of ALS onset, ranked in descending order of feature importance as monocyte, leukocyte, HGI, and HbA1c. Peripheral blood white blood cells, monocytes, HbA1c, and HGI can serve as potential diagnostic biomarkers for ALS. Combined detection can improve the diagnostic accuracy of ALS, facilitating early diagnosis and intervention, and ultimately improving patient prognosis. Further validation in cohorts including disease controls is required to confirm specificity.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, and its prognosis is closely associated with the rate of disease progression. An increasing number of studies are focusing on non-motor symptoms (NMS), particularly constipation; however, their role in the association between ALS progression and survival remains unclear. This study investigated the contribution of NMS to the relationship between ALS progression and survival. In this multicenter prospective cohort study, 150 patients with ALS were followed for 9 months. VanderWeele’s four-way decomposition method was applied to evaluate the interaction and mediation effects of NMS on the association between ALS progression and survival. Compared with slow progression (ΔFS < 0.47/month), moderate progression (ΔFS 0.47–1.1/month) and fast progression (ΔFS > 1.1/month) were associated with increased excess relative risk of mortality. Constipation demonstrated significant interaction effects with ALS progression. The combined interaction components accounted for 79.55% and 91.15% of the excess relative risk in the moderate- and fast-progression groups, respectively. In contrast, no significant pure natural indirect effect was observed. Constipation primarily functions as an interacting factor rather than a mediator in the association between ALS progression and survival. These findings highlight the potential prognostic relevance of constipation, particularly among patients with more rapidly progressive disease.

INTRODUCTION:Nasolabial fold (NLF) correction is commonly evaluated at 6 to 12 months, yet the clinical distinction between immediate volumizing fillers and delayed biostimulatory fillers is best understood as a time-course problem rather than a single-visit comparison. This study compared the long-term efficacy trajectory and late safety profile of a poly-L-lactic acid (PLLA) dermal filler with a hyaluronic acid (HA) filler for correction of moderate-to-severe NLFs through 120 weeks after the final injection. METHODS:This multicenter randomized, evaluator-blinded, parallel-group parent trial with an observational extension enrolled adults aged 18 to younger than 65 years with bilateral Wrinkle Severity Rating Scale (WSRS) grade 3 or 4 NLFs at 6 centers in China. The parent trial followed participants for 52 weeks after the final injection; extension participants were then followed for an additional 68 weeks, giving a total follow-up of 120 weeks after the final injection. The parent trial randomized 208 participants to PLLA (n=106) or HA (n=102). The 120-week analysis included 135 participants: 63 in the PLLA group and 72 in the HA group. RESULTS:In the parent-trial full analysis set, WSRS effective correction rates were similar between PLLA and HA at 4 weeks (89.80% versus 92.78%; P=0.461) and 12 weeks (90.00% versus 88.12%; P=0.670). The treatment curves separated later, favoring PLLA at 24, 36, and 52 weeks. At 120 weeks, the WSRS effective correction rate was 55.56% (35/63) with PLLA and 25.00% (18/72) with HA (P<0.001). Participant-rated GAIS improvement was numerically greater with PLLA (73.02% versus 56.94%; P=0.108), whereas investigator-rated GAIS improvement significantly favored PLLA (80.95% versus 63.89%; P=0.024). No late device-related safety event was observed. CONCLUSION:PLLA and HA showed similar short-term efficacy through 12 weeks, whereas PLLA provided superior long-term performance through 120 weeks. These findings support PLLA as a durable biostimulatory option when sustained correction is prioritized, while also underscoring that long-term extension data should be interpreted in light of attrition and observational follow-up.

Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disorder. ALS typically progresses rapidly, leading to respiratory failure within 3 to 5 years of symptom onset. Identifying risk factors that influence disease progression and survival is critical for enhancing management strategies. The present study therefore investigated the roles of inflammatory factors and adipokines (especially adiponectin) in the progression and prognosis of ALS. The study included 80 ALS patients, with a follow-up period of 1.5 years. Survival analysis was performed using a Cox regression, with hazard ratios (HR) and 95% confidence intervals (CI) presented via forest plots. Our results indicated that ALS patients in the fast-progressing group exhibited lower levels of adiponectin (p < 0.001) and IL-10 (p < 0.001). The Cox regression and forest plot results suggest the potential of adiponectin (HR = 0.905, 95%CI: 0.866-0.946, p < 0.001), IL-10 (HR = 0.968, 95%CI: 0.951-0.986, p < 0.001), δFS (HR = 1.234, 95%CI: 1.065-1.430, p = 0.005) and ALSFRS-R (HR = 0.820, 95%CI: 0.765-0.878, p < 0.001) as potential risk factors. In addition, these risk factors are significantly associated with poor survival prognosis in high-risk populations (all p < 0.001). This study identifies adiponectin, IL-10, ALSFRS-R, and δFS as key risk factors influencing ALS progression and prognosis.

Upper limb spasticity is a common and disabling complication of stroke. Botulinum toxin type A (BoNT-A) is widely used for focal spasticity treatment, but naturally derived products may present limitations related to immunogenicity and manufacturing variability. Recombinant botulinum toxin type A, produced by genetic engineering without complexing proteins, may provide improved product consistency. This Ib/II study evaluated the safety, tolerability, and preliminary efficacy of recombinant botulinum toxin type A in adults with post-stroke upper limb spasticity.This multicenter, seamless Ib/II clinical study included an open-label dose-escalation Ib phase and a randomized, double-blind, placebo-controlled II phase. Adult patients with post-stroke upper limb spasticity received a single intramuscular injection of recombinant botulinum toxin type A or placebo. The primary endpoint in Phase II was the change from baseline in the Modified Ashworth Scale (MAS) score of the primary target muscle group at Week 4. Secondary endpoints included MAS and Tardieu scale changes in individual muscle groups, Disability Assessment Scale (DAS), Physician's Global Assessment (PGA), and immunogenicity.The Ib phase showed improvements in MAS, DAS, and PGA, indicating an early efficacy signal. In Phase II, recombinant botulinum toxin type A produced a significant reduction in MAS score of the primary target muscle group at Week 4 compared with placebo, with effects sustained through Week 12. At Week 4, the PGA score in the Eveotox® group showed a statistically significant improvement compared with the placebo group. While MAS and PGA scores showed significant improvement, DAS functional scores did not differ statistically from the placebo group at week 4. The treatment was generally well tolerated, and low incidence of antibodies were observed.Recombinant botulinum toxin type A was safe and effective in reducing post-stroke upper limb spasticity after a single administration. These results support further Phase III clinical evaluation.

Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited peripheral neuropathy and currently lacks disease-modifying therapy. PXT3003, a low-dose oral combination targeting PMP22 overexpression, has shown efficacy in two trials, while one recent confirmatory trial failed to meet its primary efficacy endpoints. In this trial, eligible participants aged 16 to 65 years with genetically confirmed mild-to-moderate CMT1A were randomly assigned to receive oral PXT3003 or placebo twice daily for 15 months. The primary endpoint was the change in the overall neuropathy limitations scale (ONLS) total score from baseline to month 15. At month 15, mean ONLS change from baseline was -0.268 (SD: 0.82) in the PXT3003 group versus 0.013 (SD: 0.65) in the placebo group, with a between-group difference of -0.249 (95% confidence interval [CI]: -0.467 to -0.030; p = 0.0257). Significant improvements were observed in the ONLS leg subscore and ankle-dorsiflexion strength. These findings support PXT3003 as a promising therapeutic option for alleviating limb symptoms in patients with CMT1A.

Objective To quantitatively evaluate sleep spindle alterations in sporadic amyotrophic lateral sclerosis (ALS) and explore their potential as biomarkers for diagnosis and phenotypic stratification. Methods In this cross-sectional study, overnight sleep electroencephalography was recorded in 97 sporadic ALS patients and 73 matched healthy controls. Sleep spindle parameters (amplitude, duration, density, frequency) were automatically analyzed at frontal leads. Multiple comparisons were controlled using the false discovery rate (FDR) approach. We used least absolute shrinkage and selection operator (LASSO) regression for diagnostic modeling and employed K-means clustering to define spindle-based subtypes. Bootstrap internal validation was performed to assess model optimism. Results After FDR correction, ALS patients showed significant spindle abnormalities predominantly in the bipolar FP12 derivation, including reduced slow spindle density (p-FDR = 0.007), reduced overall spindle density (p-FDR = 0.007), and shortened slow spindle duration (p-FDR = 0.017). A diagnostic model incorporating Epworth Sleepiness Scale score, wake after sleep onset, sleep efficiency, FP12 slow spindle density, and education years showed promising discriminative ability (apparent AUC = 0.931; optimism-corrected AUC = 0.923). Unsupervised clustering consistently revealed two distinct spindle phenotypes. The "spindle-deficient" phenotype, characterized by poorer spindle integrity, was independently associated with lower ALSFRS-R scores (OR 1.101, 95% CI 1.024-1.202, p = 0.017), lower percentage of predicted forced vital capacity (OR 1.035, 95% CI 1.010-1.065, p = 0.011), and absence of drinking history (OR 3.03, 95% CI 1.02-9.46, p = 0.049). Conclusions Sleep spindle alterations may represent a core electrophysiological feature of ALS, potentially reflecting thalamocortical dysfunction. These exploratory findings suggest that spindle parameters could serve as candidate biomarkers for disease stratification, though validation in independent longitudinal cohorts is needed before clinical application.

Importance Tetramethylpyrazine nitrone has exhibited promising results in improving motor dysfunction in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Objective To evaluate the safety and efficacy of orally administered tetramethylpyrazine nitrone in patients with ALS. Design, Setting, and Participants This phase 2, multicenter, double-masked, placebo-controlled, randomized clinical trial was conducted from December 24, 2020, through July 14, 2023, in 11 centers in China, with a 180-day follow-up. Patients aged 45 to 70 years, with ALS onset within 2 years, ALS Functional Rating Scale-Revised (ALSFRS-R) scores of at least 2 points on each item, and forced vital capacity (FVC) of at least 80% were included. Patients experienced a 1- to 4-point decrease in ALSFRS-R score during a 3-month screening period. Interventions Patients were randomly assigned 1:1:1 to receive low-dose tetramethylpyrazine nitrone (600 mg twice daily), high-dose tetramethylpyrazine nitrone (1200 mg twice daily), or placebo (twice daily) for 180 days. Main Outcomes and MeasuresThe primary outcome was change in ALSFRS-R score (range of 0-48, with lower scores indicating worse function) from baseline to 180 days. The secondary outcomes were changes in FVC, grip strength, ALS Assessment Questionnaire-40 (ALSAQ-40) score, and end point events. Safety outcomes included adverse events. Results A total of 155 patients (mean [SD] age, 55.0 [6.5] years; 115 men [74.2%]) were randomized (51 [32.9%] to the low-dose tetramethylpyrazine nitrone group, 52 [33.6%] to the high-dose tetramethylpyrazine nitrone group, and 52 [33.6%] to the placebo group). No significant differences were observed in ALSFRS-R score changes between low-dose tetramethylpyrazine nitrone (least squares [LS] mean difference, -0.89 points; 95% CI -3.25 to 1.48 points) and high-dose tetramethylpyrazine nitrone (LS mean difference, -0.20 points; 95% CI -2.48 to 2.07 points) compared with placebo. High-dose tetramethylpyrazine nitrone showed a significantly slower decline in grip strength at day 180 (LS mean difference, 2.46 kg; 95% CI, 0.15-4.76 kg). In a subgroup of patients younger than 65 years with slower disease progression, tetramethylpyrazine nitrone significantly attenuated the decline in grip strength (LS mean difference, 3.63 kg; 95% CI, 0.84-6.41 kg), bulbar scores (LS mean difference, 0.66 points; 95% CI, 0.03-1.29 points), and respiratory scores (LS mean difference, 0.54 points; 95% CI, 0.03-1.06 points). Adverse events were mostly mild or moderate, with no severe treatment-related adverse events or deaths. Conclusions and Relevance This randomized clinical trial demonstrates that tetramethylpyrazine nitrone is safe and well-tolerated in patients with ALS. There was no difference in the primary end point across the low-dose, high-dose, and placebo groups, with significant benefits in a subgroup of younger patients with slower disease progression.

PAF15 is an oncogene and is overexpressed across multiple malignancies. However, its biological role in melanoma remains largely unclear. In this research, bioinformatics analysis (GEPIA2, TCGA, CancerSEA) confirmed transcriptional PAF15 overexpression in melanoma, correlating with a poor prognosis and implicating pathways involved in cell cycle, proliferation, DNA damage, and repair. Immunohistochemical analysis further confirmed high expression of PAF15 protein in clinical melanoma tissues. Subsequently, the impact of PAF15 on melanoma cell proliferation and cell cycle progression was quantified through MTT assay and propidium iodide staining. Annexin V staining and immunofluorescence were used to assess apoptosis and DNA damage. Markers associated with these biological pathways were evaluated by western blot. Evaluation of PAF15-mediated tumorigenic effects was performed using a subcutaneous xenograft model. The results revealed that PAF15 knockdown markedly suppressed melanoma cell proliferation through the induction of G0/G1 phase cell cycle arrest. Additionally, PAF15 knockdown triggered genomic instability, as evidenced by increased DNA damage markers, and promoted caspase-dependent apoptosis. Furthermore, PAF15 knockdown suppressed the growth of xenograft tumors in vivo. Notably, these tumor-inhibiting effects of PAF15 knockdown were effectively rescued upon PAF15 reconstitution. Summed up, these findings establish PAF15 as both a prognostic indicator for unfavorable clinical outcomes and a promising therapeutic vulnerability in melanoma.

Background Recent research has underscored the critical role of long non-coding RNAs (lncRNAs) in tumorigenesis and malignancy development. Nevertheless, the role of lncRNA cytoskeleton regulator RNA (CYTOR) in the progression of melanoma remains only partially elucidated. This research seeks to explore the impact of CYTOR on melanoma development and to elucidate the molecular mechanisms involved. Methods In vitro and in vivo models were used to assess CYTOR expression levels by QPCR and Western blotting. Melanoma cell proliferation, migration, and invasion were assessed by CCK-8 assay, scratch wound assay and transwell invasion experiments. The mechanism of CYTOR promoting melanoma progression was verified in a xenograft tumor mouse model. Results Our investigation identified a marked increase in CYTOR expression levels in both melanoma tissues and cells. Experiments conducted both in vitro and in vivo revealed that CYTOR markedly stimulated melanoma cell proliferation, migration, and invasion. Dual-luciferase reporter assays confirmed the direct binding of miR-485-5p to CYTOR, and glucose-6-phosphate isomerase (GPI) was identified as a direct target of miR-485-5p.

IntroductionAmyotrophic lateral sclerosis (ALS) is a rare, devastating neurodegenerative disease that affects upper and lower motor neurons, resulting in muscle atrophy, spasticity, hyperreflexia, and paralysis. Inflammation plays an important role in the development of ALS, and associated with rapid disease progression. Current observational studies indicate the thinning of cortical thickness in patients with ALS is associated with rapid disease progression and cognitive changes. However, the effects of inflammatory cytokines on cortical thickness in patients with ALS are unclear. Here, we investigated the relationship between inflammatory cytokines and cortical thickness in patients with ALS.MethodsWe evaluated 51 patients with ALS for inflammatory cytokines including interleukin (IL)-4, interferon (IFN)-α, IL-1β, IL-2, IL-5, IL-12, tumor necrosis factor (TNF)-α, IL-6, IL-10, IL-8, IL-17, and IFN-γ and analyzed the correlation between these indicators and the ALS functional rating scale-revised (ALSFRS-R) score or disease progression rate (ΔFS score). Twenty-six patients with ALS and 26 controls were studied using whole-cortex analysis, and post-hoc analyses were performed to examine the correlation between brain cortical thickness and ALSFRS-R or ΔFS scores.ResultsIL-4, IFN-α, IL-1β, and IL-2 levels were significantly correlated with ALSFRS-R scores, and the IL-2 level was significantly correlated with ΔFS scores. After controlling for age and sex, the ALS group had thinner cortexes in multiple clusters across the brain than the control group. Further analyses revealed that cortical thickness in the right superior temporal and lingual gyrus regions was inversely correlated with ΔFS scores. There was a significant positive correlation between the clusters in the right lingual cortex and IL-2 level.ConclusionThese results suggest cortical thickness was reduced in patients with ALS in motor and non-motor cortical areas. Inflammatory factors (especially IL-2) were correlated with cortical thickness, and both were related to the disease progression rate, suggesting IL-2 plays an important role in ALS.

Background:Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron degeneration and glial activation. The coupling of global blood oxygen level-dependent (gBOLD) signals with cerebrospinal fluid (CSF) inflow dynamics is a novel non-invasive biomarker, which is applied to assess the relationship between lymphatic function and ALS. Objective:The gBOLD-CSF coupling was used to assess the glymphatic system dysfunction related to ALS, and the relationship between this disease and the glymphatic system was further explored by combining the diffusion tensor imaging index of the perivascular space (DTI-ALPS) and the volume fraction of the choroid plexus (choroid plexus volume [CPV]/intracranial total volume [TIV]). Methods:We conducted a systematic analysis and comparative study of the imaging indicators and clinical data of 41 patients with ALS and 43 healthy controls (HC). Results:ALS patients showed significantly reduced gBOLD-CSF coupling (p < 0.001), reduced ALPS index (p < 0.001), and increased CPV fraction (p < 0.001). The area under the ROC curve (AUC) were 0.790 (gBOLD-CSF), 0.760 (ALPS index), and 0.748 (CPV fraction). A diagnostic model for ALS was developed based on gBOLD-CSF coupling, ALPS index, and CPV fraction with an AUC of 0.897 (0.830-0.964). The calibration curve demonstrates that the model exhibits strong consistency. The results of the Decision Curve Analysis (DCA) further indicate that the nomogram possesses substantial clinical utility. Conclusion:This study identified that gBOLD-CSF coupling has diagnostic value for ALS and developed a diagnostic model by combining the ALPS index and CPV fraction, which has good diagnostic efficacy and clinical application value.

OBJECTIVE:To investigate the role and mechanisms of Erianin in treating alopecia areata. METHODS:A C3H/HeJ AA mouse model was established using skin transfer or adoptive T-cell transfer. All mice received either systemic or topical treatments. Photographic documentation was used to monitor hair growth, which was quantified using G*Power software. Infiltrating inflammatory markers in the skin were assessed using immunofluorescence staining, and the infiltrating immune cell populations in the skin and subcutaneous draining lymph nodes (SDLNs) were analyzed using flow cytometry. RESULTS:Erianin effectively inhibited the function of effector T cells, significantly suppressing Alopecia Areata (AA) in C3H/HeJ transplanted mice. It also reversed systemic manifestations of AA and effectively promoted hair growth in AA mice. CONCLUSION:Erianin demonstrates a potent therapeutic effect on AA, primarily through modulation of T cell immune function.

To investigate the involvement and mechanisms of PPARα agonists in alopecia areata (AA). AA models were established using skin grafting, adoptive T-cell transfer, and TCR retrograde T-cell transfer methods. Relative PPARα expression levels in C3H/HeJ AA mice and AA patients were evaluated using qPCR and immunohistochemistry (IHC). Hair changes in mice following treatment were documented photographically, while immunofluorescence staining was employed to assess inflammatory factor dynamics in the skin. Additionally, ELISA and flow cytometry were used to analyze AA-related immune factors and cell populations in treated mice. PPARα agonists demonstrated protective effects in C3H/HeJ skin graft AA models and TCR transgenic AA mice, promoting early reversal of AA. They effectively inhibited T effector cell function and exerted immunomodulatory effects. The PPARα signaling pathway plays a key role in AA pathogenesis. PPARα agonists show therapeutic potential for AA as an inflammatory condition.

IntroductionDepression is a severe neuropsychiatric manifestation in patients with amyotrophic lateral sclerosis (ALS), substantially impacting their quality of life and exacerbating caregiver burden, due to the need for different approaches in clinical care. However, a predictive model for the risk of depression in patients with ALS is lacking. This study aimed to develop and validate a predictive model using routinely accessible clinical and laboratory indicators to identify patients at high risk of depression.MethodsPatients with ALS who were hospitalized in the Department of Neurology at the Second Hospital of Hebei Medical University between March 2017 and December 2024 were included. Basic clinical data, laboratory test results, and relevant questionnaire scores were collected, and patients were divided into depressed and non-depressed groups. The least absolute shrinkage and selection operator regression and multivariate logistic regression analyses were applied for variable selection and model construction. Model performance was evaluated using the area under the receiver operating characteristic curve, calibration curves, decision curve analysis, and clinical impact curves, with internal validation performed via bootstrap resampling.ResultsDepression was observed in 33.9% of patients. Significant predictors included educational level, sleep disorders, anxiety, Revised Amyotrophic Lateral Sclerosis Functional Rating Scale total scores, C-reactive protein levels, and the Systemic Inflammation Response Index. The final model demonstrated good predictive accuracy and clinical applicability. A depression risk scoring table was further developed based on the coefficients of the logistic regression.ConclusionThe nomogram and the scoring table offer a reliable and practical approach for clinicians to identify patients with ALS who are at high risk for depression and enable early psychological intervention in clinical settings.

Background: Amyotrophic lateral sclerosis (ALS) is a rapidly progressing and rare neurodegenerative disease. Therefore, evaluating the risk factors affecting the survival of patients with ALS is crucial. Constipation, a common but overlooked symptom of ALS, can be effectively managed. It is currently unknown whether constipation contributes to the progression and survival of ALS. Objectives: This study aimed to investigate the association between constipation and ALS development and survival using a novel overlap-weighted (OW) method to enhance the robustness and reliability of results. Design: This prospective matching nested case-control (NCC) study was conducted within an ongoing ALS cohort at the Second Hospital of Hebei Medical University. Baseline data were collected from patients meeting the inclusion and exclusion criteria, with constipation as the exposure factor. A 9-month follow-up was conducted, with death as the endpoint event. Methods: We primarily used the OW method in NCC studies to examine the association between constipation and ALS development and survival. Weighted Cox proportional hazards model was used to assess risk factors associated with overall survival. Survival differences between the two groups were analyzed using Kaplan-Meier’s plots and log-rank tests. Finally, the bioinformatic analysis explored common pathways between ALS and constipation. Results: Among the 190 patients included, the prevalence of constipation was 50%. Patients with ALS constipation exhibited faster disease progression ( p < 0.001), with a positive correlation between constipation severity and progression rate ( r = 0.356, p < 0.001). The constipation group had poorer survival before and after OW (log-rank test, p < 0.0001). In the Cox proportional hazards model of 114 patients, constipation was a risk factor for ALS both before (hazard ratio (HR) = 5.840, 95% confidence interval (CI) = 1.504–22.675, p = 0.011) and after (HR = 5.271, 95% CI = 1.241–22.379, p = 0.024) OW. Conclusion: Constipation in individuals with ALS is associated with faster disease progression and reduced survival rates, potentially through the peroxisome proliferator-activated receptor pathway.