Tourette syndrome （TS） is a highly prevalent neurodevelopmental disorder in children， clinically characterized primarily by motor and/or vocal tics. Its pathogenesis is associated with hyperactivity of the dopaminergic system in the basal ganglia， and current medical treatments are limited by adverse reactions and unsatisfactory efficacy. In traditional Chinese medicine （TCM）， TS is classified under categories such as "liver wind" and "convulsions"， and is considered to be closely related to liver dysregulation. Uncariae Ramulus Cum Uncis （URCU） is a commonly used wind-dispelling herb. URCU has a clearly defined origin and a rich chemical composition， with alkaloids as its major active constituents， including rhynchophylline and isorhynchophylline. Its plasma components include multiple prototype alkaloids， which exhibit metabolic differences and phenomena such as enterohepatic circulation. Its brain-entering components possess blood-brain barrier permeability， and their distribution is associated with pharmacological effects. In recent years， increasing numbers of studies have focused on the pharmacological effects and mechanisms of the active components of URCU in the treatment of TS. This article systematically reviews the mechanisms by which URCU and its main active constituents exert therapeutic effects on TS from the following aspects： regulation of monoamine and amino acid neurotransmitters to improve neurotransmitter system imbalance， neuroprotection and intervention in neuroinflammation-related pathways； antioxidant effects through activation of antioxidant signaling pathways， and immunomodulatory functions influencing immune cells and the gut microbiota. In addition， the clinical application of compound formulas containing URCU in the treatment of TS is summarized， with the aim of providing new perspectives for further research on the pharmacological mechanisms of URCU and the treatment of TS.

Tourette syndrome （TS） is a highly prevalent neurodevelopmental disorder in children， clinically characterized primarily by motor and/or vocal tics. Its pathogenesis is associated with hyperactivity of the dopaminergic system in the basal ganglia， and current medical treatments are limited by adverse reactions and unsatisfactory efficacy. In traditional Chinese medicine （TCM）， TS is classified under categories such as "liver wind" and "convulsions"， and is considered to be closely related to liver dysregulation. Uncariae Ramulus Cum Uncis （URCU） is a commonly used wind-dispelling herb. URCU has a clearly defined origin and a rich chemical composition， with alkaloids as its major active constituents， including rhynchophylline and isorhynchophylline. Its plasma components include multiple prototype alkaloids， which exhibit metabolic differences and phenomena such as enterohepatic circulation. Its brain-entering components possess blood-brain barrier permeability， and their distribution is associated with pharmacological effects. In recent years， increasing numbers of studies have focused on the pharmacological effects and mechanisms of the active components of URCU in the treatment of TS. This article systematically reviews the mechanisms by which URCU and its main active constituents exert therapeutic effects on TS from the following aspects： regulation of monoamine and amino acid neurotransmitters to improve neurotransmitter system imbalance， neuroprotection and intervention in neuroinflammation-related pathways； antioxidant effects through activation of antioxidant signaling pathways， and immunomodulatory functions influencing immune cells and the gut microbiota. In addition， the clinical application of compound formulas containing URCU in the treatment of TS is summarized， with the aim of providing new perspectives for further research on the pharmacological mechanisms of URCU and the treatment of TS.

Objective:To develop a novel fibroblast activation protein (FAP) cyclic peptide imaging agent, Al 18F-FAP-NOX, evaluate its in vitro and in vivo properties, and explore its feasibility of PET/CT imaging in tumors with FAP positive expression. Methods:Al 18F-FAP-NOX was manually synthesized. The in vitro stability of Al 18F-FAP-NOX was determined using radio high performance liquid chromatography (HPLC). The lipid water partition coefficient log P, in vitro cell uptake experiments, microPET/CT imaging and biodistribution in 293T-FAP tumor-bearing mice were conducted to preliminarily evaluate the pharmacokinetics and biological efficacy of Al 18F-FAP-NOX. Afterwards, a patient (male, 65 years old) with lung cancer underwent Al 18F-FAP-NOX PET/CT imaging. Results:Al 18F-FAP-NOX was successfully synthesized with a yield of (26.28±2.31)% without attenuation correction ( n=4), and the radiochemical purity was more than 95%. Al 18F-FAP-NOX exhibited good stability and hydrophilicity (log P=-3.02±0.08, n=5). In cell assays, the uptake of Al 18F-FAP-NOX in HT1080-FAP cells reached the plateau phase at 15 min ((7.31±0.53) percentage activity of injection dose per million cells (%ID/mio cells)), exhibiting high cellular uptake. The uptake of Al 18F-FAP-NOX could be significantly inhibited by 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-FAP-2286. The microPET/CT results of 293T-FAP tumor-bearing mice in vivo showed that Al 18F-FAP-NOX was highly uptaken in FAP-positive tumor tissues (60 min: (12.47±1.66) percentage activity of injection dose per gram of tissue (%ID/g)), while the uptake was very low in FAP-negative tumors. The biodistribution results were similar to the microPET/CT imaging results of tumor-bearing mice. The human clinical imaging showed an abnormal increase in Al 18F-FAP-NOX uptake (SUV max 5.5) of the lung cancer lesions. Conclusions:A novel cyclic peptide radiopharmaceutical, Al 18F-FAP-NOX, demonstrates good stability and hydrophilicity. It can be quickly distributed to tumor tissue in vivo. The human clinical PET/CT imaging shows certain diagnostic ability of Al 18F-FAP-NOX for lung cancer lesions. It is a promising cyclic peptide agent for PET imaging.

Objective:To systematically evaluate the safety and efficacy of the novel fibroblast activation protein (FAP)-targeted tracer 64Cu-FAP inhibitor (FAPI)-XT117 in patients with malignant solid tumors, and to compare with 18F-FDG. Methods:This self-controlled study was conducted on fifteen patients (8 males, 7 females; age (60 ±9) years) with malignant solid tumors from the First Affiliated Hospital of Guangzhou Medical University between July 2023 and December 2023. Each subject underwent 64Cu-FAPI-XT117 PET/CT at 30, 60, and 120min post-injection and was assigned to three dose cohorts (111MBq, 148MBq, and 185MBq; 5 patients in each cohort), and safety assessments were conducted within 24h after injection. In addition, all patients underwent 18F-FDG PET/CT at 60min post-injection. Time-activity curves were generated for 64Cu-FAPI-XT117, and the dosimetry was calculated. Image quality was evaluated using a 5-point Likert scale, and the optimal injected activity and imaging time point were determined. The paired t test was used to compare differences of the lesion detection count and SUV max between 64Cu-FAPI-XT117 and 18F-FDG PET/CT. Results:64Cu-FAPI-XT117 was well tolerated, with no adverse events reported. Time-activity curves of 68Ga-FAPI-XT117 revealed prominent uptake in the uterus, while the background activity in other organs remained low, with the whole-body effective dose of (0.0084±0.0021)mSv/MBq. The optimal imaging time point for 64Cu-FAPI-XT117 PET/CT was 60min post-injection, with an optimal administered activity of 111MBq. Compared with 18F-FDG, 64Cu-FAPI-XT117 demonstrated significantly higher uptake and more lesions in lymph-node metastases (SUV max: 8.6±3.8 vs 15.3±6.8, t=2.33, P=0.048; number of lesions: 8.3±5.4 vs 15.0±6.4; t=4.21, P=0.003) and distant metastases (SUV max: 11.8±3.7 vs 20.9±7.2, t=3.66, P=0.022; number of lesions: 7.0±3.2 vs 12.4±3.7, t=2.86, P=0.046). Conclusions:64Cu-FAPI-XT117 PET/CT is well tolerated in patients with solid tumors, with a controllable radiation risk. Moreover, it outperforms 18F-FDG PET/CT in the assessment of metastases.

Objective To develop a scientific,systematic and operational competency evaluation index system for primary and sec-ondary school special education teachers based on World Health Organization rehabilitation competency frame-work(RCF),integrating the inclusive teacher frameworks of United Nations Educational,Scientific and Cultural Organization(UNESCO)and European Union(EU)as well as China's Professional Standards for Special Educa-tion Teachers(Trial).Methods A core competency framework and content for special education teachers in primary and secondary schools was constructed based on RCF,using a systematic analysis of UNESCO and EU policy documents and the Minis-try of Education's Professional Standards for Special Education Teachers(Trial).On this foundation,a corre-sponding competency evaluation index system was developed.Results The competency framework for primary and secondary school special education teachers comprised five compe-tency domains and two supporting dimensions,including 25 core competency modules and 59 evaluation points.The five competency domains were educational and teaching practice,professional ethics and values,profession-al learning and development,management and collaborative leadership,and educational research and innovation.The two supporting dimensions were professional beliefs and core values.Conclusion The competency evaluation index system for primary and secondary school special education teachers em-phasizes educational equity,inclusive principles,and values of care and justice.It can be used for competency di-agnosis and assessment of teachers at different developmental stages,as well as for designing continuing educa-tion courses and professional development plans.

Objective:To explore changes in the along the perivascular space (ALPS) index in patients with relapsing-remitting multiple sclerosis (RRMS) and investigate its association with cerebral injury.Methods:The study was a cross-sectional investigation. A total of 32 patients diagnosed with RRMS (RRMS group) and 30 healthy controls (HC) were retrospectively collected from March 2023 to July 2024 at the Affiliated Hospital of Inner Mongolia Medical University. All participants underwent MRI scans, including high-resolution three-dimensional (3D) T 1-weighted magnetization-prepared rapid gradient echo sequence, 3D fluid-attenuated inversion recovery sequence, and diffusion spectrum imaging. Regions of interest (ROI) were manually placed on the axial plane of the lateral ventricular body based on fractional anisotropy (FA) maps to obtain diffusion rates along the x, y, and z axes for ALPS index calculation. Tract-based spatial statistics was used to extract diffusion values from the white matter skeleton of the participants, including FA, mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and quantitative anisotropy (QA). Lesion growth algorithms were employed to extract white matter lesion volume (WMLV) and number (WMLN). After lesion filling on T 1 images, brain segmentation was performed, and normalized gray matter volume (nGMV), normalized white matter volume (nWMV), and normalized cerebrospinal fluid volume (nCSFV) were obtained by normalizing with total intracranial volume(TIV). Independent sample t-tests, Mann-Whitney U tests, and χ2 tests were used to assess differences in clinical and imaging indicators between the RRMS and HC groups. Spearman′s rank correlation analysis was performed to evaluate the relationship between the ALPS index and clinical and imaging indicators. Results:The ALPS index, FA, and nGMV values were lower in the RRMS group compared to the HC group ( t=2.42, P=0.019; Z=4.85, P<0.001; t=2.56, P=0.013), while the RD value was significantly higher in the RRMS group ( Z=-2.42, P=0.015). No significant difference was found in other clinical and imaging indicators between the two groups ( P>0.05). In the RRMS group, the ALPS index was negatively correlated with WMLV ( r=-0.43, P=0.018) and positively correlated with FA ( r=0.45, P=0.012). There was no correlation between ALPS index and MD values, AD values, RD values, QA values, WLMN values, nGMV values, nMWV values, nCSFV values, TIV values, and duration of the disease ( P>0.05). Conclusions:Patients with RRMS exhibit abnormal diffusion in the perivascular spaces at the lateral ventricular body, suggesting possible glymphatic system dysfunction. The ALPS index is associated with demyelination and neurodegeneration.

Objectives:To investigate the clinical efficacy of the smiley face rod(SFR)technique in treating lumbar spondylolysis with grade Ⅰ spondylolisthesis.Methods:A total of 22 patients(18 males,4 females)with lumbar spondylolysis and grade Ⅰ spondylolisthesis treated with the SFR segmental fixation technique in our department from January 2019 to December 2024 were retrospectively analyzed.The age of the patients was 12-55(28.7±12.6)years old,the body mass index(BMI)was 18-29kg/m2(22.7±3.4kg/m2),and preoperative symptom duration was 6-60(12.3±14.3)months.The patients were followed up for 6-19(9.1±4.5)months.The operative time and intraoperative blood loss volume were recorded.Before opearation,at 3 months and 6 months after operation,visual analogue scale(VAS)for low back pain,Oswestry disability index(ODI),and Japanese Orthopaedic Association(JOA)scores were recorded to evaluate the clinical outcomes.Imaging exami-nations(X-ray,CT)were performed before operation and at 6 months after operation to measure preoperative and postoperative disc height(DH),slip distance(SD),slip rate,lumbar lordosis angle,and range of motion(ROM)at the surgical and adjacent segments to assess the improvement of spondylolisthesis and ROM,as well as the pars defect healing status.The correlations between age,BMI,preoperative disease duration and isthmus bone healing rate were studied.Results:The operative time was 131.8±32.8min(range:86-200min),and intraoperative blood loss was 86.4±41.4mL(range:50-150mL).Significant improvements in VAS,ODI and JOA scores were observed at 3 months and 6 months versus preoperative values(P＜0.05).Slip distance,slip percentage,and lumbar lordosis angle significantly decreased at 6 months versus preoperatively(P＜0.05).No significant differences were observed in DH ratio or ROM between the surgical and adjacent segments preoperatively and at 6 months(P＜0.05).At 6-month follow-up,complete bilateral pars bony union was achieved in 18 cases(81.82％),partial union(including unilateral or other types)in 3 cases(13.63％),and nonunion in 1 case(4.55％).Age,BMI,and preoperative symptom duration showed potential influence on bone healing.Conclusions:In the treatment of lumbar spondylolysis with grade Ⅰ spondylolisthesis,SFR can effectively enhance postoperative lumbar stability,significantly alleviate low back pain symptoms,preserve lumbar mobility,and mitigate disc height collapse to a certain extent.

OBJECTIVE To establish a population pharmacokinetic(PopPK)model to predict the PK characteristics of GLS-010 in humans.METHODS Fifty-eight cynomolgus monkeys were used,18 of which were randomly divided into three groups and received a single intravenous infusion of GLS-010 at doses of 2,6,and 18 mg·kg-1,respectively.The rest were randomly assigned to four groups and received multiple intravenous infusions of GLS-010 at doses of 0,5,25,and 100 mg·kg-1,respectively,once a week(quaque week,qw)for five consecutive weeks.Blood samples were collected before and after administration.The concentrations of GLS-010 in the monkey serum were measured using a validated enzyme-linked immunosorbent assay,while those of anti-drug antibodies(ADA)in the cynomolgus monkey serum were determined by ultra-sensitive electrochemiluminescence immunoassay.The PK data on GLS-010 in cynomolgus monkeys was obtained,and the drug-time curves were plotted.A PopPK model was constructed using non-compartmental analysis and evaluated by goodness-of-fit plots and visual predictive checks.The constructed PopPK model was used to predict the PK characteristics in humans,which were finally compared with actual Phase Ⅰ clinical study results for validation.RESULTS The predictive results of the PopPK model were highly consistent with the actual Phase Ⅰ clinical study results.The model was able to predict the human PK characteristics under various dosing regimens,including 1 mg·kg-1 quaque 2 weeks(q2w),4 mg·kg-1(q2w),240 mg(q2w),240 mg(q3w),and 10 mg·kg-1(q2w).The predicted maximum plasma concentrations(Cmax)were 24.8,99.1,85.0,85.0,and 247.8 mg·L-1,respectively,and the AUC0-336h was 4 902.0,20 060.0,17 147.7,22 145.7(AUC0-504h),and 50 817.6 mg·h·L-1,respectively.The safety risks for the corresponding dosing regimens were 47.3,11.6,13.5,10.5,and 4.6,respectively.The predicted receptor occupancy at steady state(ROss)at Cmax,average plasma concentration(Cavg),and minimum plasma concentration(Cmin)were 38.8％,72.7％,69.4％,64.1％and 87.2％,29.1％,63.8％,60.0％,49.8％and 82.1％,21.9％,55.5％,51.3％,36.3％and 76.7％,respectively.CONCLUSION The PopPK model can effectively predict the human PK characteristics under different dosing regimens with high consistency with actual Phase Ⅰ clinical study results,which can serve as an important reference for selection of safe and effective doses for first-in-human research.

Objective To evaluate the clinical efficacy of acupuncture combined with Modified Zuojin Granules in treating reflux esophagitis(RE)with liver-stomach disharmony syndrome.Methods A total of 100 patients diagnosed with liver-stomach disharmony syndrome RE were enrolled from October 2022 to October 2024 at Zigong First People's Hospital.The patients were randomly assigned to the observation group and the control group,with 50 cases in each group.The control group was treated with Modified Zuojin Granules,while the observation group was given acupuncture plus Modified Zuojin Granules,both group were treated for 4 weeks.The changes in the traditional Chinese medicine(TCM)syndrome scores,24-hour esophageal acid reflux parameters(frequency and longest duration),serum gastrointestinal hormones[gastrin(GAS),motilin(MTL),vasoactive intestinal peptide(VIP)],gut microbiota composition(Lactobacillus,Bifidobacterium,Enterococcus,Enterobacter)were observed.The adverse reactions and safety profiles were evaluated.Results(1)Both groups showed significant improvement in TCM syndrome scores(P＜0.05),with greater improvement in the observation group,and the differences were statistically significant(P＜0.05).(2)After treatment,both groups of patients showed significant improvements in the number of gastric reflux episodes in the oesophagus over 24 hours and the longest reflux duration(P＜0.05).The observation group demonstrated significantly better improvements in the number of gastric reflux episodes in the oesophagus over 24 hours and the longest reflux duration compared to the control group,with statistically significant differences(P＜0.05).(3)After treatment,the serum levels of GAS,MTL,and VIP in both groups of patients were significantly improved(P＜0.05).The observation group showed significantly better improvement in serum GAS,MTL,and VIP levels compared to the control group,with statistically significant differences(P＜0.05).(4)After treatment,the levels of Lactobacilli and Bifidobacteria in both groups increased significantly compared to before treatment(P＜0.05),while the levels of Enterococci and Enterobacteria were significantly decreased(P＜0.05).The improvement in intestinal microbiota levels was more pronounced in the observation group,with statistically significant differences(P＜0.05).(5)The overall efficacy rate was 96.00％(48/50)in the observation group and 80.00％(40/50)in the control group.The observation group demonstrated superior efficacy compared to the control group,with statistically significant differences(P＜0.05).(6)The incidence of adverse reactions in the observation group was 8.00％(4/50),while that in the control group was 12.00％(6/50).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion The combined therapy significantly improves clinical symptoms,modulates gastrointestinal hormones and gut microbiota,demonstrating excellent efficacy and safety for liver-stomach disharmony syndrome RE.

Objective Uranium compounds are critical materials in the nuclear industry, and their mining, processing, and use pose occupational exposure risks. Epidemiological studies have shown that uranium exposure can impair health, with acute uranium poisoning primarily causing structural and functional damage to the kidneys. Currently, the molecular mechanisms underlying uranium-induced kidney injury remain unclear, and traditional biological models used in toxicological research are inadequate for simulating the human microenvironment. This study employed a human kidney organoid model system to elucidate the nephrotoxic mechanisms of uranyl ions, providing a scientific basis for the prevention and control of uranium poisoning. Methods Kidney organoids were constructed using the human embryonic stem cell line H1 and exposed to solutions with different uranyl ion concentrations. Morphological observation, ATP detection, reactive oxygen species detection, apoptosis assay, and untargeted metabolomics analysis were performed. Mechanisms of toxicity were further explored through KEGG pathway enrichment analysis. Results Uranium exposure led to structural damage in the organoids, accompanied by a dose-dependent decrease in ATP levels, accumulation of reactive oxygen species, and increased apoptosis rate. After 24-hour exposure to 300 μmol/L uranium, significantly disturbed differential metabolites and five core metabolic pathways were identified. Conclusion Uranium induces oxidative stress, mitochondrial dysfunction (ATP reduction), and metabolic disorder (disruption of phospholipid/amino acid metabolism), which synergistically cause DNA damage, apoptosis, and/or necrosis. These findings provide new insights into the mechanisms of uranium-induced kidney injury and support the development of prevention and control strategies.