ObjectiveTo analyze the research status and development trends of non-pharmacological therapies for post-stroke spasticity (PSS) over the past two decades. MethodsRelevant literatures on non-pharmacological rehabilitation of PSS published from January, 2004 to June, 2024 were retrieved from Web of Science Core Collection. CiteSpace 6.3.R6 and VOSviewer 1.6.18 were used for visualization analysis. ResultsA total of 780 publications were included. The annual number of publications showed an overall upward trend. China, the USA, and Italy contributed the highest number of publications. The Hong Kong Polytechnic University and researcher Noureddin Nakhostin Ansari were identified as the most influential institution and author, respectively. High-frequency keywords and cluster labels included electric stimulation, transcranial magnetic stimulation, robot and acupuncture. ConclusionOver the past 20 years, researches on non-pharmacological therapies for PSS have remained active, with hotspots focusing on diverse interventions such as electrical stimulation, magnetic stimulation and robot-assisted therapy.

Ulcerative colitis （UC） is a chronic nonspecific inflammatory intestinal disease with a complex pathogenesis. Its recurrent attacks easily lead to persistent intestinal mucosal damage， resulting in a year-by-year increase in incidence and imposing a heavy burden on patients. Currently， the treatment of UC mainly relies on corticosteroids， immunosuppressants， and aminosalicylate preparations. However， these therapies are limited by significant side effects， strong drug resistance， and poor long-term prognosis. As one of the important inflammatory pathways， the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway can regulate the occurrence and development of UC through multiple pathways by modulating multiple downstream targets. Therefore， the JAK2/STAT3 signaling pathway offers a new research direction for the treatment of UC. Numerous studies have shown that the JAK2/STAT3 signaling pathway plays an important role in intestinal inflammatory responses， intestinal mucosal barrier damage， T helper cell 17 （Th17）/regulatory T cell （Treg） immune imbalance， intestinal epithelial cell apoptosis， and oxidative stress. Chinese medicine has attracted increasing attention because of its unique advantages， including fewer side effects， individualized diagnosis and treatment， and enhancement of efficacy with reduction of toxicity. In addition to traditional Chinese herbal formulas， more Chinese medicine monomers and extracts have played key roles because of their more precise therapeutic targets. In recent years， many studies have confirmed that Chinese medicine can exert therapeutic effects on UC by interfering with the JAK2/STAT3 signaling pathway， thereby alleviating intestinal inflammatory responses， repairing the intestinal mucosal barrier， regulating the balance of Th17/Treg immune cells， inhibiting intestinal epithelial cell apoptosis， and suppressing oxidative stress. This article summarizes and reviews recent research progress in this field from three aspects， including an overview of the JAK2/STAT3 signaling pathway， the relationship between the JAK2/STAT3 signaling pathway and UC， and the regulatory mechanisms of traditional Chinese medicine， with the aim of providing a theoretical basis for the future clinical treatment of UC and drug development.

Ulcerative colitis （UC） is a chronic nonspecific inflammatory intestinal disease with a complex pathogenesis. Its recurrent attacks easily lead to persistent intestinal mucosal damage， resulting in a year-by-year increase in incidence and imposing a heavy burden on patients. Currently， the treatment of UC mainly relies on corticosteroids， immunosuppressants， and aminosalicylate preparations. However， these therapies are limited by significant side effects， strong drug resistance， and poor long-term prognosis. As one of the important inflammatory pathways， the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway can regulate the occurrence and development of UC through multiple pathways by modulating multiple downstream targets. Therefore， the JAK2/STAT3 signaling pathway offers a new research direction for the treatment of UC. Numerous studies have shown that the JAK2/STAT3 signaling pathway plays an important role in intestinal inflammatory responses， intestinal mucosal barrier damage， T helper cell 17 （Th17）/regulatory T cell （Treg） immune imbalance， intestinal epithelial cell apoptosis， and oxidative stress. Chinese medicine has attracted increasing attention because of its unique advantages， including fewer side effects， individualized diagnosis and treatment， and enhancement of efficacy with reduction of toxicity. In addition to traditional Chinese herbal formulas， more Chinese medicine monomers and extracts have played key roles because of their more precise therapeutic targets. In recent years， many studies have confirmed that Chinese medicine can exert therapeutic effects on UC by interfering with the JAK2/STAT3 signaling pathway， thereby alleviating intestinal inflammatory responses， repairing the intestinal mucosal barrier， regulating the balance of Th17/Treg immune cells， inhibiting intestinal epithelial cell apoptosis， and suppressing oxidative stress. This article summarizes and reviews recent research progress in this field from three aspects， including an overview of the JAK2/STAT3 signaling pathway， the relationship between the JAK2/STAT3 signaling pathway and UC， and the regulatory mechanisms of traditional Chinese medicine， with the aim of providing a theoretical basis for the future clinical treatment of UC and drug development.

With the increase of patients with end-stage renal disease and the increasing complexity of dialysis machines,the traditional fixed cycle empirical preventive maintenance model has revealed its disadvantages,such as wasted resources and frequent failures.This paper focuses on the optimization of the dialysis machine's proactive maintenance plan based on risk as-sessment,analyzing its cutting-edge working principles,and involving advanced technologies such as semi-permeable membranes and intelligent magnetic levitation drives.It also explores composite failures,such as nanoscale biological contamination,and provides solutions.It innovatively proposes to build a multi-dimensional integrated risk assessment system,collect heterogeneous data from multiple sources,establish a risk factor library,and develop a dynamic adaptive risk model.Based on this,a proactive maintenance strategy is designed to break the fixed cycle and use an intelligent platform to flexibly schedule maintenance accord-ing to the risk level.By integrating pre-diagnosis and self-healing technologies,it can predict and automatically repair minor fail-ures in advance using microsensors.This promotes the intelligence of the dialysis machine-related industry,but future efforts are still needed to cultivate cutting-edge technologies to protect kidney health.

Objective:To preliminarily evaluate the efficacy and safety of a domestically developed bilateral interventional ultrasound renal denervation (RDN) system in patients with uncontrolled hypertension despite antihypertensive medication.Methods:A multicenter, single-arm trial was conducted. Patients with uncontrolled hypertension (≥2 antihypertensive drugs) were enrolled from April 2023 to April 2024 at the Second Affiliated Hospital of Chongqing Medical University, West China Hospital of Sichuan University, and the Second Affiliated Hospital of Harbin Medical University. RDN was performed using the UltraCure? bilateral interventional ultrasound system via femoral or brachial artery access. Multi-segmental "quadrant-based" ablation was performed in bilateral main renal arteries and branches/accessory arteries (diameter≥4 mm). Primary endpoints were changes in office systolic blood pressure (SBP) and 24-hour daytime SBP at 2-and 6-months post-procedure. The primary safety endpoints included the incidence of major adverse events, device-related adverse events, and puncture site complications.Results:Ten patients, mean aged 47.1 years, including 9 male, successfully completed RDN. At 2 and 6 months post-procedure, office SBP decreased by (19.7±15.2) mmHg ( P=0.002, 1 mmHg=0.133 kPa) and (13.8±13.9) mmHg ( P=0.013) from baseline, while the 24-hour daytime SBP decreased by (13.4±10.6) mmHg ( P=0.004) and (11.2±9.2) mmHg ( P=0.004). Apart from one case of a limited distal renal artery dissection, no other serious device/procedure-related adverse events were observed. At 6-month follow-up, the estimated glomerular filtration rate remained stable ((85.3±18.3) ml·min -1·1.73 m -2 vs. (82.3±19.2) ml·min -1·1.73 m -2, P=0.41). No renal artery stenosis was detected. Conclusions:The domestic interventional ultrasound RDN system could effectively reduce office and ambulatory blood pressure in patients with uncontrolled hypertension, demonstrating a favorable safety profile. Long-term efficacy requires confirmation through large-scale randomized controlled trials.

OBJECTIVE: To explore the clinical features and genetic basis of a male patient with Kennedy disease(KD) presenting as secondary infertility. METHODS: A male patient who had presented at Yantai Yuhuangding Hospital in August 2023 for secondary infertility for 5 years was selected as the study subject. Clinical data, laboratory findings, and auxiliary examination of the patient were collected. Peripheral blood samples were obtained from the patient and his family members. Following DNA extraction, whole-exome sequencing (WES) was carried out. Pathogenicity of candidate variant was predicted by bioinformatics analysis. Fluorescence probe PCR-capillary electrophoresis was employed to analyze the trinucleotide CAG repeat sequence variation in the AR gene to rule out dynamic mutation. This study was approved by the Ethics Committee of Yantai Yuhuangding Hospital (Ethics No.: 2024-697). RESULTS: The patient had presented with non-obstructive azoospermia and elevated androgen sensitivity index. Ultrasound scan indicated small testicular volume and seminal vesicle atrophy. WES and bioinformatics analysis revealed abnormal amplification in the patient's AR gene. Fluorescence probe PCR and capillary electrophoresis confirmed that both the proband and his nephew had harbored 52 CAG trinucleotide repeats in exon 1 of the AR gene, confirming the diagnosis of KD. The proband's mother, elder sister, and daughter were identified as carriers of the variant, while his second elder sister did not carry the mutation. CONCLUSION As a rare X-linked recessive genetic disease, KD mainly manifests with muscle weakness, myasthenia gravis and myofascial tremor, while cases with infertility and non-obstructive azoospermia as the initial symptoms are rare and can be easily missed. Diagnosis made by genetic testing needs to be taken seriously by the clinicians.
Humans ; Male ; Bulbo-Spinal Atrophy, X-Linked/diagnosis* ; Adult ; Infertility, Male/genetics* ; Receptors, Androgen/genetics* ; Exome Sequencing ; Mutation ; Pedigree ; Trinucleotide Repeats

The 5-hydroxytryptamine 2A receptor (5-HT_2AR) is one of the key targets in the development of novel antidepressants. To develop new antidepressants targeting the 5-HT_2A receptor, this study established a high-throughput screening method for drugs targeting the 5-HT_2A receptor based on the principle of detecting calcium flux signals. The immunofluorescence assay and western blotting were employed to evaluate receptor expression levels in the 5-HT_2AR-CHO cell line. The reaction system parameters, including cell seeding density, DMSO concentration, and dye incubation time, were optimized with Z'-factor and signal window values as evaluation indicators. The specificity, precision, stability, and applicability of the method were assessed. Results indicated that the 5-HT_2AR-CHO cell line stably expressed high levels of the 5-HT_2A receptor. The optimized screening method involved a reaction system with 10 000 cells/well, 0.2% DMSO, and 2 h incubation with Calcium 6 dye. The method demonstrated excellent specificity, with inter-batch precision below 10% for the detection of 5-hydroxytryptamine (5-HT) at low, medium, and high concentrations. Testing four compounds that target the 5-HT_2A receptor- agonists 2,5-dimethoxy-4-iodoamphetamine (DOI), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD), along with the antagonist MDL100907-yielded Z'-factors (at EC₈₀) greater than 0.85 and signal window values over 0.91. The EC₅₀ values of these compounds were in the nanomolar range, and their potency rank order aligned with previously reported data, confirming the reliability of the established method. When being applied to the detection of 38 known active compounds, the method efficiently identified 5-HT_2A receptor agonists and antagonists while showing no response to non-target compounds. In conclusion, this study successfully constructs a high-throughput screening approach for 5-HT_2A receptor-targeting drugs based on calcium flux signals. The method possesses strong specificity, high sensitivity, and robust stability, being suitable for screening antidepressants targeting the 5-HT_2A receptor.
High-Throughput Screening Assays/methods* ; Receptor, Serotonin, 5-HT2A/metabolism* ; Animals ; CHO Cells ; Cricetulus ; Calcium Signaling/drug effects* ; Antidepressive Agents/pharmacology* ; Humans ; Serotonin 5-HT2 Receptor Antagonists/pharmacology* ; Calcium/metabolism*

Depression is increasingly prevalent among adolescents and can profoundly impact their lives. However, the early detection of depression is often hindered by the time-consuming diagnostic process and the absence of objective biomarkers. In this study, we propose a novel approach for depression detection based on an affective brain-computer interface (aBCI) and the resting-state electroencephalogram (EEG). By fusing EEG features associated with both emotional and resting states, our method captures comprehensive depression-related information. The final depression detection model, derived through decision fusion with multiple independent models, further enhances detection efficacy. Our experiments involved 40 adolescents with depression and 40 matched controls. The proposed model achieved an accuracy of 86.54% on cross-validation and 88.20% on the independent test set, demonstrating the efficiency of multimodal fusion. In addition, further analysis revealed distinct brain activity patterns between the two groups across different modalities. These findings hold promise for new directions in depression detection and intervention.
Humans ; Male ; Female ; Adolescent ; Case-Control Studies ; Depression/diagnosis* ; Early Diagnosis ; Rest ; Electroencephalography/methods* ; Brain-Computer Interfaces ; Models, Psychological ; Reproducibility of Results ; Affect/physiology* ; Photic Stimulation/methods* ; Video Recording ; Brain/physiopathology*

Objective:To preliminarily evaluate the efficacy and safety of a domestically developed bilateral interventional ultrasound renal denervation (RDN) system in patients with uncontrolled hypertension despite antihypertensive medication.Methods:A multicenter, single-arm trial was conducted. Patients with uncontrolled hypertension (≥2 antihypertensive drugs) were enrolled from April 2023 to April 2024 at the Second Affiliated Hospital of Chongqing Medical University, West China Hospital of Sichuan University, and the Second Affiliated Hospital of Harbin Medical University. RDN was performed using the UltraCure? bilateral interventional ultrasound system via femoral or brachial artery access. Multi-segmental "quadrant-based" ablation was performed in bilateral main renal arteries and branches/accessory arteries (diameter≥4 mm). Primary endpoints were changes in office systolic blood pressure (SBP) and 24-hour daytime SBP at 2-and 6-months post-procedure. The primary safety endpoints included the incidence of major adverse events, device-related adverse events, and puncture site complications.Results:Ten patients, mean aged 47.1 years, including 9 male, successfully completed RDN. At 2 and 6 months post-procedure, office SBP decreased by (19.7±15.2) mmHg ( P=0.002, 1 mmHg=0.133 kPa) and (13.8±13.9) mmHg ( P=0.013) from baseline, while the 24-hour daytime SBP decreased by (13.4±10.6) mmHg ( P=0.004) and (11.2±9.2) mmHg ( P=0.004). Apart from one case of a limited distal renal artery dissection, no other serious device/procedure-related adverse events were observed. At 6-month follow-up, the estimated glomerular filtration rate remained stable ((85.3±18.3) ml·min -1·1.73 m -2 vs. (82.3±19.2) ml·min -1·1.73 m -2, P=0.41). No renal artery stenosis was detected. Conclusions:The domestic interventional ultrasound RDN system could effectively reduce office and ambulatory blood pressure in patients with uncontrolled hypertension, demonstrating a favorable safety profile. Long-term efficacy requires confirmation through large-scale randomized controlled trials.

With the increase of patients with end-stage renal disease and the increasing complexity of dialysis machines,the traditional fixed cycle empirical preventive maintenance model has revealed its disadvantages,such as wasted resources and frequent failures.This paper focuses on the optimization of the dialysis machine's proactive maintenance plan based on risk as-sessment,analyzing its cutting-edge working principles,and involving advanced technologies such as semi-permeable membranes and intelligent magnetic levitation drives.It also explores composite failures,such as nanoscale biological contamination,and provides solutions.It innovatively proposes to build a multi-dimensional integrated risk assessment system,collect heterogeneous data from multiple sources,establish a risk factor library,and develop a dynamic adaptive risk model.Based on this,a proactive maintenance strategy is designed to break the fixed cycle and use an intelligent platform to flexibly schedule maintenance accord-ing to the risk level.By integrating pre-diagnosis and self-healing technologies,it can predict and automatically repair minor fail-ures in advance using microsensors.This promotes the intelligence of the dialysis machine-related industry,but future efforts are still needed to cultivate cutting-edge technologies to protect kidney health.