BACKGROUND:Abrocitinib, a selective Janus kinase 1 inhibitor, is an effective therapy for moderate-to-severe atopic dermatitis (AD). However, evidence guiding dose reduction during long-term maintenance in real-world practice remains limited, and determinants of successful dose tapering are unclear. OBJECTIVE:To evaluate the feasibility of abrocitinib dose reduction and identify clinical and immunological features associated with tapering. METHODS:In this prospective real-world study, 66 adults with moderate-to-severe AD received standard-dose abrocitinib for 12 weeks, followed by individualized dose adjustment based on disease control. Clinical outcomes and serum cytokine profiles were assessed longitudinally to characterize treatment responses and immunological correlates of dose reduction. RESULTS:Baseline disease severity was comparable between groups defined by dose-adjustment outcomes. Patients requiring dose maintenance or escalation had a longer disease duration and higher prevalence of atopic comorbidities and family history, whereas those achieving dose reduction tended to be older. By Week 12, the dose-reduction group achieved significantly lower Eczema Area and Severity Index scores, pruritus numerical rating scale scores and eosinophil counts. These differences persisted during long-term follow-up despite dose reduction. Cytokine analyses demonstrated significantly lower IL-13 levels at Week 12, with consistent trends towards reduced inflammatory activity during maintenance therapy. CONCLUSIONS:Successful abrocitinib dose reduction appears to occur in a clinically distinct subgroup characterized by shorter disease duration, lower atopic burden and deeper early treatment responses. Patients achieving dose tapering exhibited a more quiescent inflammatory profile. These findings support an individualized treatment-optimization strategy aimed at maintaining long-term disease control with the minimal effective dose.

ObjectiveVitamin K1 (VK1) supplementation is an important therapeutic agent for the treatment of hemorrhage due to VK1 deficiency. It can be administered orally, intramuscularly, or via intravenous injection. This study was conducted to evaluate the bioequivalence of VK1 micelle produced by Hainan Biotech Pharmaceutical Co., Ltd. compared to the original drug KONAKION®MM when administered orally.MethodsThis was a randomized, open-label, two-period, single-dose, crossover bioequivalence study conducted under both fasting and fed conditions, with 28 participants in each condition. Participants received 10 mg oral dose of test (T) or reference (R) drug in the first period and the opposite drug in the second period, with a 9-day washout. Blood concentrations of the E and Z isomers of VK1 were measured at 26 or 29 time points for fasting condition or fed condition, respectively. Bioequivalence was determined if the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of the peak concentration (Cmax), the area under the concentration-time curve from time zero to the last measurable concentration (AUC0–t) and the extrapolated area under the curve from time zero to infinity (AUC0−∞) after log transformation for VK1 E isomer fell within the 80.00%–125.00% range under both fasting and fed conditions. The International Normalized Ratio (INR) was used as an exploratory endpoint to observe changes following dosing. Safety assessments included vital signs and electrocardiograms (ECGs).ResultsUnder fasting conditions, the 90% CIs for the GMRs of Cmax, AUC0-t, and AUC0−∞ for the VK1 E isomer were 99.17%–119.24%, 103.91%–121.13%, and 105.72%–122.77%, respectively. Under fed conditions, the corresponding 90% CIs were 83.56%–120.82%, 84.98%–124.63%, and 83.97%–124.32%. All values fell within the 80.00%–125.00% equivalence margin, confirming bioequivalence between the two formulations. There were no significant changes in INR. The safety profile was favorable, with no serious adverse events (SAEs) or grade 3 or higher adverse events (AEs) reported.ConclusionThe VK1 micelle produced by Hainan Brilliant Pharmaceutical Co., Ltd. is bioequivalent to the original drug KONAKION®MM, supporting its approval as a generic product by oral administration. It demonstrated good safety and tolerability in healthy Chinese subjects.Clinical Trial Registrationhttp://www.chinadrugtrials.org.cn/index.html, identifier CTR20223408; https://www.chictr.org.cn/, identifier ChiCTR2500096211.

Vagus nerve stimulation offers a promising strategy for seizure control but remains limited by its invasive delivery. Here, we reveal electroacupuncture (EA), an ancient neuromodulatory technique rooted in traditional Chinese medicine, at specific somatic acupoints linked to the vagal-brain axis to treat epilepsy and delineate the precise underlying neural mechanisms. We demonstrate that EA at the Dazhui (GV14) acupoint exhibits broad-spectrum antiseizure efficacy across multiple seizure models. Anatomical and functional analyses reveal that GV14 activates the vagal afferents and recruits neurons in the caudal nucleus of the solitary tract (cNTS), which are essential for seizure suppression. Using targeted recombination in active populations and chemogenetic manipulation, we show that GV14 EA suppresses seizures via the recruitment of a defined cNTS-locus coeruleus-amygdala circuit. Furthermore, through vagal afferent activity screening, we identify Yaoqi (EXB9) as an alternative therapeutic acupoint that activates a shared neural pathway to robustly attenuate seizures. Importantly, thread-embedding acupuncture at GV14 or EXB9 produces sustained seizure reduction in a chronic epilepsy model. Together, these findings elucidate a functional vagal-brain circuit underlying EA-induced seizure control and support its translational potential as a minimally invasive neuromodulatory strategy to replace vagal stimulation for epilepsy treatment.

Auricular stimulation therapy (AST), encompassing transcutaneous auricular vagus nerve stimulation (taVNS) and auricular acupuncture, is gaining prominence as a non-pharmacological intervention for Depressive Disorders. Accumulating evidence from systematic reviews and randomized controlled trials (RCTs) demonstrate its efficacy in mitigating symptoms of Depressive Disorders, postpartum depression (PPD), post-stroke depression (PSD), with effects comparable to first-line antidepressants and a superior tolerability profile. Beyond symptom relief, AST is associated with improvements in sleep quality, cognitive function, and may serve as an adjunct to reduce antidepressant dosage. This review aims to systematically evaluate the current evidence on AST for depressive disorders and discuss its potential as a safe, effective, and medication-sparing clinical strategy.

OBJECTIVE:To study the application value of Lindegaard ratio evolution trajectory monitored by transcranial Doppler ultrasound (TCD) in predicting the prognosis of cerebral vasospasm (CVS) after traumatic brain injury (TBI), and to provide reference for early clinical improvement of prognosis. METHODS:A total of 194 patients with CVS after TBI admitted to China Tianjin Huanhu Hospital from February 2022 to May 2024 were selected. The evolution trajectory of Lindegaard ratio on the 1st, 3rd, 7th and 14 th day of TCD monitoring of CVS patients after TBI was analyzed. The clinical data and Lindegaard ratio trajectory of different prognostic groups were compared, and the predictive value of Lindegaard ratio evolution trajectory on the prognosis of CVS patients after TBI was analyzed. RESULTS:The Lindegaard ratio showed an increasing trend from day 1 to day 7, and decreased at day 14 (P < 0.05). The Lindegaard ratio of the high trajectory subgroup was higher than that of the median trajectory subgroup and the low trajectory subgroup on the 1st, 3rd, 7th and 14th day of treatment (P < 0.05). There were significant differences in Glasgow Coma Scale (GCS) score, epidural hematoma, CVS severity, Fisher grade, Lindegaard ratio trajectory and multiple trauma between the two groups with different prognosis (P < 0.05). GCS score at admission, epidural hematoma, severity of CVS, Fisher grade, Lindegaard ratio trajectory, and multiple injuries were all independent influencing factors of poor prognosis in patients with CVS after TBI (P < 0.05). The GCS score at admission, epidural hematoma, severity of CVS, Fisher grade, Lindegaard ratio trajectory, and multiple injuries were analyzed. The results showed that the AUC of the combination of the above indicators in predicting the prognosis of patients with CVS after TBI was 0.772 (95%CI: 0.697-0.848). CONCLUSIONS:TCD monitoring of Lindegaard ratio evolution trajectory can effectively predict the prognosis of patients with CVS after TBI. Among them, the risk of poor prognosis in patients with high Lindegaard ratio trajectory is significantly increased, which can provide reference for clinical individualized intervention and improvement of patient prognosis.

BACKGROUND:In the treatment of post-stroke depression (PSD), acupuncture has emerged as a therapeutic option; however, the exact mechanisms underlying its efficacy remain unclear. Prior research suggests acupuncture may improve PSD symptoms by regulating M1/M2 microglial polarization, reducing the release of inflammatory factors and inflammatory-associated damage. OBJECTIVE:The aim of the present study was to explore whether manual acupuncture (MA) can mediate microglial polarization via the silence information regulator/nuclear factor κB (Sirt1/NF-κB) pathway, thereby reducing inflammatory responses in the brains of rats exhibiting PSD and improving depressive behavior. METHODS:Thirty male rats were divided into a middle cerebral artery occlusion (MCAO) group, PSD group, PSD + MA group, PSD + MA + Sirt1 inhibitor group, and PSD + MA + NS (normal saline) group. Acupuncture was applied 6 days a week for 4 weeks at GV26, GV20 and bilateral PC6 and SP6. In the PSD + MA + Sirt1 inhibitor group, nicotinamide (NAM), a specific inhibitor of Sirt1, was slowly injected into the frontal lobe with a stereotactic injector 1 h before acupuncture. Behavioral tests were conducted after modeling and intervention, including the sucrose preference test (SPT) and open field test (OFT), and body weight was monitored. Following the tests, specimens of the dorsolateral frontal lobe were taken to evaluate molecular markers. Immunofluorescence staining was employed to determine the expression levels of M1 microglial markers CD16/Iba1 and M2 microglial markers CD206/Iba1 in the dorsolateral prefrontal cortex. mRNA expression of CD16/intrinsic nitric oxide synthase (iNOS) and CD206/arginase (Arg)-1 was detected by q-RT-PCR. Western blot analysis was used to quantify protein expression of Sirt1, total p65 and phosphorylated p65 (p-p65) proteins. Interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor (TNF)-α levels were quantified using ELISA. RESULTS:Depression-like behavior of PSD model rats was reduced by MA. Acupuncture promoted transformation of microglia from M1 to M2 in the prefrontal lobe, thereby decreasing expression of pro-inflammatory factors (IL-1β, IL-6 and TNF-α) and increasing expression of anti-inflammatory IL-10 after PSD. In addition, expression of Sirt1 in the prefrontal lobe increased following MA, while expression of p65/p-p65 was reduced, indicating activation of the Sirt1/NF-κB pathway. These findings suggest that M1 to M2 microglial polarization was closely related to Sirt1/NF-κB pathway activation following MA. CONCLUSION:MA promoted the transformation of microglia from M1 to M2 in the prefrontal lobe of PSD rats, reduces the inflammatory response and improves depression-like behavior in rats. These effects were associated with activation of the Sirt/NF-κB pathway.

BACKGROUND:Previous clinical studies have demonstrated that transcutaneous auricular vagal nerve stimulation (taVNS) alleviates functional dyspepsia (FD) symptoms. But the underlying brain functional mechanism remains unclear. This study aimed to explore the brain modulation effects of taVNS treating FD by using resting-state functional magnetic resonance imaging (rs-fMRI). METHOD:Twenty-one patients with FD and 30 healthy controls (HCs) were enrolled. The FD subjects (FDs) were treated by taVNS and conducted with brain fMRI scans before and after 8-week treatment, HCs underwent one fMRI scan upon inclusion. Voxel-based functional connectivity (FC) and correlation analyses were used to explore the brain modulation effects of taVNS on FDs. RESULT:After treatment, FD patients showed significant improvement in symptoms. At baseline, FD patients exhibited significantly increased functional connectivity (FC) between the left dorsal anterior insula (dAI) and the left dorsolateral prefrontal cortex (DLPFC) compared with healthy controls. After taVNS treatment, FC between insular subregions-particularly the anterior insula (AI)-and multiple brain regions, including the DLPFC, amygdala, parahippocampus, and cuneus/lingual/calcarine gyrus, was widely reduced. CONCLUSION:This study demonstrated that FD patients exhibit abnormal FC between the AI and DLPFC. TaVNS effectively alleviated clinical symptoms in FD, which may be associated with its modulation of FC between the AI with central executive network (CEN), limbic system, and visual network (VN).

The lack of any viable therapy for Alzheimer’s disease (AD) evoked the study and utilization of neuromodulation. 40-Hz transauricular vagal nerve stimulation (taVNS) preliminarily showed effectiveness in mice with partial cognitive impairment in our previous work, yet 3 major problems remained unresolved. (1) Can 40-Hz taVNS rescue the cognition of mice exhibiting total cognitive impairment? (2) Are the cognition-rescuing effects of taVNS specific to 40 Hz stimulation? (3) Via P2X7R signaling? Thus, 3 parts were divided to address the above issues in this work using 9-month-old wild-type (WT) and APPswe/PS1dE9 (APP/PS1) mice. Behavioral examinations for cognition; western blotting (WB), enzyme-linked immunosorbent assays (ELISA) for Aβ load; WB and ELISA for the P2X7R signaling pathway; Nissl staining for neuroprotective effects were employed. 3 findings can be derived. (1) 40-Hz taVNS rescues cognition of the APP/PS1 mice aged 9 months (but is not effective in WT mice of the same age). (2) The cognition-rescuing effects of taVNS in APP/PS1 mice are frequency-specific, which is 40 Hz in this work (neither 8-Hz taVNS nor 80-Hz taVNS works). (3) The hippocampal P2X7R signaling is a critical mediator of the observed effects (inhibiting P2X7R had similar effects to 40-Hz taVNS, which counteracted activating P2X7R). Therefore, 40-Hz taVNS shows potential as a viable therapy option for AD, with the P2X7R being a prominent target.

Spinal cord injury (SCI) can disrupt segmental reflex modulation and alter inhibitory regulation within spinal circuits. However, how these electrophysiological and molecular alterations vary across different injury severities remains unclear. This study examined H-reflex modulation and lumbar glutamic acid decarboxylase (GAD) and potassium-chloride cotransporter 2 (KCC2) expression across SCI severities in rats. Forty adult female Sprague-Dawley rats were assigned to a Sham group or four contusion groups defined by impactor drop height (6.25, 12.5, 25, or 50 mm; n = 8 per group). At 5 weeks after surgery, the Hmax/Mmax ratio and rate-dependent depression (RDD) of the tibial nerve H-reflex were assessed. Immunofluorescence and Western blotting were used to assess GAD and KCC2 expression in the lumbar spinal cord. Compared with the Sham group, all SCI groups exhibited significantly higher Hmax/Mmax ratios. RDD was significantly attenuated mainly in the moderate-to-severe contusion groups, although intergroup differences varied across stimulation frequencies. GAD and KCC2 expression showed overall decreases with greater injury severity. Correlation analyses demonstrated positive associations of injury severity with the Hmax/Mmax ratio and mean normalized H/M ratios at 5 and 10 Hz, whereas inverse associations were observed with GAD and KCC2 expression. SCI of different severities was associated with altered segmental reflex modulation and reduced lumbar GAD and KCC2 expression, although the electrophysiological and molecular changes did not show a simple one-to-one relationship.

Background:Despite significant advancements in endovascular treatment (EVT) over the past decade, symptomatic intracerebral hemorrhage (sICH) persists as a serious complication, especially in patients with acute ischemic stroke (AIS) related to intracranial atherosclerotic stenosis (ICAS), which is characterized by complex and calcified plaques. The present study aimed to develop a predictive nomogram for assessing the risk of sICH in AIS patients with ICAS and large-vessel occlusion (LVO) who undergo EVT. Methods:We analyzed data from 183 patients with acute ischemic stroke (AIS) due to intracranial atherosclerotic stenosis-related large vessel occlusion (ICAS-LVO) who underwent endovascular treatment (EVT) between January 2022 and December 2023. The primary safety outcome was the incidence of symptomatic intracranial hemorrhage (sICH). A nomogram was developed based on a multivariable logistic regression model, and the calibration of the model was evaluated using Spiegelhalter's Z-test. Results:In our developed nomogram, elevated D-dimer levels (odds ratio [OR] 2.87; 95% confidence interval [CI], 1.53-5.39; p = 0.001), longer onset-to-recanalization time (OR 1.00; 95% CI, 1.00-1.01; p = 0.004), and larger core infarct volume (OR 1.04; 95% CI, 1.01-1.06; p = 0.002) were identified as independent predictors of symptomatic intracranial hemorrhage (sICH) in stroke patients undergoing endovascular treatment (EVT). The goodness-of-fit of the model was confirmed by a non-significant Spiegelhalter's Z-test (p = 0.941). Conclusion:A nomogram integrating D-dimer levels, onset-to-recanalization time, and core infarct volume offers a reliable and practical method for estimating the risk of symptomatic intracranial hemorrhage in acute ischemic stroke patients with intracranial atherosclerotic stenosis-related large vessel occlusion receiving endovascular therapy.

Transcutaneous electrical cranial-auricular acupoints stimulation (TECAS) has been recognized as a promising therapeutic approach for depression. However, the efficacy of TECAS varies among individuals, and it remains unclear which populations are more sensitive to this treatment. This study aims to investigate the impact of TECAS on brain functional networks by analyzing electroencephalogram (EEG) data, distinguishing between responders and non-responders. We included 57 patients with mild to moderate depression and collected EEG data at baseline and after 8 weeks of TECAS treatment. Our analysis focused on identifying baseline network characteristics correlating with positive TECAS responses. The results indicate that patients with higher network integration and synchrony, particularly those with elevated delta frequency band network topology parameters, showed better outcomes with TECAS. Additionally, using a nonlinear regression model, we predicted the effectiveness of TECAS with a correlation coefficient of 0.52 and an RMSE of 17.3 %. Machine learning techniques were further employed to identify responders and non-responders at baseline, with the XGBoost classifier achieving the highest accuracy of 82.91 %. These findings suggest that specific EEG network features can serve as predictors for the efficacy of TECAS in treating depression.

Introduction Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) affects around 35%–50% of men during their lifetime. The efficacy of current oral medication for CP/CPPS remains limited. Recent studies demonstrated that vagus nerve stimulation may improve chronic pelvic and abdominal pain. Accordingly, transcutaneous auricular vagus nerve stimulation (taVNS) might represent a promising, non-invasive therapeutic approach for the clinical management of CP/CPPS.Methods and analysis The trial of Transcutaneous Auricular vagus nerve Stimulation for moderate to severe Chronic Prostatitis/CPPS is a prospective, randomised, sham-controlled trial with a 1:1 allocation ratio. Participants will be assigned randomly to either the taVNS group or the sham-taVNS group. The intervention period will consist of a 4-week treatment (a total of 40 sessions), followed by an 8-week follow-up period. The primary outcome is the change from baseline in the National Institutes of Health Chronic Prostatitis Symptom Score Index total score at week 4. Secondary outcomes include the International Prostate Symptom Score Scale, European Quality of Life 5-Dimensions-5-Levels questionnaire, Self-Rating Anxiety Scale and Self-Rating Depression Scale. Safety assessments will be conducted throughout the entire study period.Ethics and dissemination This study protocol and informed consent documents were reviewed and approved by the Institutional Review Board of Guang’anmen Hospital, China Academy of Chinese Medical Sciences (approval number: 2023-250 KY). Written informed consent will be obtained from all participants and/or their legal guardians prior to trial participation. The findings will be disseminated through publication in a peer-reviewed journal and presentations at scientific conferences. The research data will be made available on reasonable request.Trial registration number NCT06287970.

Despite its high prevalence, the precise mechanisms underlying major depressive disorder (MDD) remain incompletely understood. Growing evidence identifies mitochondrial dysfunction, including abnormalities in mitochondrial DNA, impaired bioenergetics, disrupted quality control, and redox imbalance, as a central pathological feature of MDD. Beyond deficits in energy production, mitochondria function as upstream regulators of neuroinflammation. Mitochondria derived damage associated molecular patterns and excessive reactive oxygen species activate innate immune signaling, while inflammatory challenges in turn compromise mitochondrial integrity. This bidirectional and self-reinforcing interaction between mitochondrial dysfunction and inflammation may contribute to disease onset, progression, and clinical heterogeneity. Preclinical and clinical studies indicate that conventional antidepressants gradually restore mitochondrial function while suppressing oxidative and inflammatory stress, whereas rapid-acting agents such as ketamine induce acute metabolic reprogramming and mitophagy, enabling swift functional recovery. Mechanistically distinct interventions, including mitochondria targeted antioxidants, metabolic modulators, and psychedelic compounds, further highlight the therapeutic potential of targeting mitochondrial pathways. By integrating current evidence, this review delineates mitochondrial-inflammation crosstalk in MDD and supports mitochondrial regulation as a promising target for novel antidepressant strategies.

Background:Although successful recanalization of the occluded artery is achieved, no-reflow phenomenon (NRP) becomes a main contributor to poor prognosis in patients with acute ischemic stroke. There are some laboratory results to represent biomarkers of the no-reflow phenomenon. However, few studies have characterized the metabolomic signature of NRP. Using high-performance liquid chromatography-tandem mass spectrometry (LC-MS)-based method, this study aims to characterize the plasma metabolites associated with NRP. Methods:A total of 34 patients with acute large vessel occlusion in anterior circulation who underwent successful thrombectomy with final angiographic expanded Treatment in Cerebral Infarction score of 2c-3 score were enrolled (19 without NRP and 15 with NRP). Fasting venous blood collected 24 h after the procedure was centrifuged and subjected to metabolomic analysis. Results:We identified 29 differentially expressed plasma metabolites, the majority of which were phosphatidylcholine (PC) species. Among them, PC(20:4(5Z,8Z,11Z,14Z)/P-16:0) showed the most significant alteration and exhibited robust predictive performance (AUC = 0.846). The most prominently disrupted metabolic pathway was glycerophospholipid metabolism, particularly PC-mediated pathways, which appeared to play a central role in the association with of NRP. Conclusion:This study depict the plasma metabolic profile of NRP patients following stroke thrombectomy, and discover that phosphatidylcholine-dominated metabolites and related pathways may play a potential role in the occurrence of NRP. These metabolic biomarkers demonstrate promising discriminative ability and may help identify high-risk patients at an early stage, providing new targets for mechanism research and therapeutic intervention.

OBJECTIVE:Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to ameliorate symptoms of both functional dyspepsia (FD) and depression/anxiety, while the central mechanism underlying taVNS effects on depression and anxiety in FD remains unclear. The aim of this study was to investigate taVNS-induced depression-like behavioral changes and cerebral activity alterations in a rodent model of FD. METHODS:Neonatal Sprague-Dawley (SD) rats were gavaged with iodoacetamide (IA) to induce a FD model. taVNS was performed for 30 min once daily for 14 days consecutively. The open field test (OFT) and forced swimming test (FST) were conducted to assess depression-like behaviors. The amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo) were derived from resting-state functional magnetic resonance imaging. Correlations between differential ALFF and ReHo values and depression-like behaviors were analyzed to identify taVNS-related central changes. RESULTS:taVNS increased both horizontal and vertical scores in the OFT and reduced the immobility time of the FST. After taVNS intervention, the ALFF and ReHo values of the right brainstem were decreased. Conversely, the ALFF values of the left molecular layer of the cerebellum and the ReHo values of the right entorhinal cortex were increased. The horizontal score of the OFT was negatively correlated with the ALFF of the right brainstem. Both the vertical score of the OFT and the immobility time of the FST were negatively correlated with the ReHo values of the entorhinal cortex. CONCLUSION:taVNS alleviates depressive state in FD rats, possibly mediated by enhancing local neural coordination in the right entorhinal cortex and suppressing spontaneous neural activity in the right brainstem. These findings support further exploration of taVNS as a candidate approach for FD-related depression.

STSA-1002 is a fully human monoclonal antibody targeting C5a, which plays a critical role in the pathogenesis of virus-induced acute respiratory distress syndrome ARDS (v-ARDS). We investigated safety, pharmacokinetics, pharmacodynamics, and anti-drug antibodies of increasing multiple intravenous doses of STSA-1002 in healthy adults. In vitro studies, STSA-1002 was a high-affinity, selective anti-human C5a monoclonal antibody blocking C5a-mediated reactive oxygen species (ROS) production. Building on the published preclinical results, a randomized, double-blind, placebo-controlled, dose-escalation study was done at a Phase I unit in China. A total of 60 adverse events (AEs) were reported. In the STSA-1002 group (n = 20), 47 AEs occurred in 18 participants (90.0%), corresponding to a mean of 2.6 AEs per participant. In the placebo group (n = 6), 13 AEs occurred in all 6 participants (100%), corresponding to a mean of 2.2 AEs per participant. Grade 2 or greater study drug-related adverse events included neutrophil count decreased, white blood cell count decreased, and aminotransferase increased. Cmax and AUC0-t increased in an approximately dose-proportional manner. After the first dose, the mean concentration of free C5a in all dose groups was suppressed to below the lower limit of quantification. This suppression was maintained in all health volunteers until D42 (5 mg/kg) and D56 (10 mg/kg and 20 mg/kg) after multiple doses. Besides, STSA-1002 could downregulate the levels of myeloperoxidase (MPO), neutrophil elastase (NE), and proteinase 3 (PR3). Overall, multiple infusions of STSA-1002 up to 20 mg/kg appear to be safe and well tolerated in healthy participants in China. The safety, PK, and PD data support the continued evaluation of STSA-1002 in larger Phase II studies.Clinical Trial Registration:https://clinicaltrials.gov/, ID NCT05497635.

Painful diabetic neuropathy (PDN) is a common complication of diabetes that substantially impairs quality of life and remains challenging to manage. Spinal cord stimulation (SCS), including high-frequency (HF-SCS), low-frequency (LF-SCS), and burstDR (burstDR-SCS) modalities delivered with the De Ridder algorithm, has emerged as a therapeutic option for patients with inadequate response to conventional medical management (CMM). However, the comparative efficacy and safety profiles of these specific SCS modalities remain unclear. A systematic search identified 1,243 records, from which seven studies involving 698 patients met the inclusion criteria and were analyzed using a random-effects Bayesian network meta-analysis framework with minimally informative priors. Primary outcomes included the proportion of patients achieving ≥ 50

RATIONALE:Aberrant circular RNA (circRNA) expression is implicated in various diseases, but the regulatory mechanisms remain poorly understood. Our previous work identified circSCMH1 as a brain repair-associated circRNA, prompting investigation into its biogenesis regulation. METHODS:We combined computational analysis of RNA-binding protein (RBP) binding sites in flanking intronic regions with transcriptomic sequencing to identify potential circSCMH1 regulators. Molecular biology experiments including RNA immunoprecipitation and functional assays were performed to validate the interaction between candidate RBPs and circSCMH1 precursor sequences. RESULTS:Polypyrimidine tract binding protein 1 (PTBP1) was identified as a key regulator binding specifically to the 800-882 segment at the 3' end of circSCMH1's flanking intron. This binding event inhibited back-splicing and reduces circSCMH1 production. Functional studies demonstrated that PTBP1-mediated suppression of circSCMH1 exacerbates post-stroke brain injury. CONCLUSIONS:Our study reveals a novel molecular mechanism whereby PTBP1 regulates circSCMH1 biogenesis through suppression of back-splicing. These findings advance understanding of circRNA regulatory networks and suggest potential therapeutic targets for stroke recovery.