Objective:To explore the factors associated with the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) in the treatment of neuropathic pain (NP) following spinal cord injury (SCI).Methods:This was a retrospective study of 89 SCI survivors with NP receiving high-frequency rTMS. Those with a ≥30% reduction in their Numeric Rating Scales (NRS) scores after 2 weeks of treatment were termed Responders ( n=36), with the others classified as non-responders ( n=53). Demographic data (gender, education level, age), SCI characteristics (injury etiology, injury severity, neurological injury level, injury duration), NP characteristics (pain type, pain intensity, analgesic use), functional assessment (Modified Ashworth Scale score, Spinal Cord Independence Measure score, Modified Barthel Index score, American Spinal Injury Association motor/sensory score) were collected. Least absolute shrinkage and selection operator (LASSO) regression was used for variable selection, followed by binary logistic regression to identify factors associated with treatment efficacy. Results:Among the 89 patients, 36 (40.4%) were Responders to high-frequency rTMS. Binary logistic regression revealed that those with a cervical spinal cord injury and/or spasticity and women were more likely to respond to high-frequency rTMS.Conclusions:Female gender, cervical spinal cord injury, and spasticity are independent factors predicting rTMS efficacy in treating SCI, with spasticity demonstrating the strongest association.

The blue fluorescent carbon dots(TMCDs)and cyan fluorescent carbon dots(TMCDs-H2O)were synthesized fromm-phenylenediamine and tricarballylic acid through air-assisted melting polymerization and one-step hydrothermal method,respectively.Air purging could effectively inhibit the side reactions and reduce the derivative structures in the carbon dots product.The structure and morphology of these two materials were systematically characterized using liquid nuclear magnetic resonance spectroscopy(NMR),mass spectrometry(MS),and transmission electron microscopy.Compared to TMCDs-H2O((3.12±0.63)nm),TMCDs showed a smaller average particle size(approximately(1.85±0.02)nm).The NMR and MS analysis revealed that although the main structure of both types of carbon dots was similar,TMCDs exhibited a simpler structure with higher degree of polymerization.These results suggested that supramolecular interactions might introduce numerous small molecule derivatives into TMCDs-H2O particles,resulting in lower polymerization degree,multiple substructures,and larger particle size characteristics for this material.When employed as chemical sensors for metal ion detection,in the linear range of 1×10-5-5×10-4 mol/L,the detection limits of Fe3+by TMCDs and TMCDs-H2O were 3.3×10-6 mol/L and 3.8×10-6 mol/L,respectively.The experimental results demonstrated that the recoveries of CDs and inductively coupled plasma optical emission spectrometer(ICP-OES)were similarity,whereas TMCDs displayed a considerable relative standard deviation.This study demonstrated that endogenously derived structures in CDs could enhance the performance of metal ion sensing.

Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1 st January 2024 and 1 st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.
Humans ; Male ; Insulin-Like Growth Factor II/metabolism* ; Infertility, Male/genetics* ; DNA Damage ; Adult ; Inflammation/metabolism* ; Spermatozoa/metabolism* ; Semen Analysis ; Semen/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Histones/metabolism* ; Interleukin-1beta/metabolism*

Objective:To explore the factors associated with the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) in the treatment of neuropathic pain (NP) following spinal cord injury (SCI).Methods:This was a retrospective study of 89 SCI survivors with NP receiving high-frequency rTMS. Those with a ≥30% reduction in their Numeric Rating Scales (NRS) scores after 2 weeks of treatment were termed Responders ( n=36), with the others classified as non-responders ( n=53). Demographic data (gender, education level, age), SCI characteristics (injury etiology, injury severity, neurological injury level, injury duration), NP characteristics (pain type, pain intensity, analgesic use), functional assessment (Modified Ashworth Scale score, Spinal Cord Independence Measure score, Modified Barthel Index score, American Spinal Injury Association motor/sensory score) were collected. Least absolute shrinkage and selection operator (LASSO) regression was used for variable selection, followed by binary logistic regression to identify factors associated with treatment efficacy. Results:Among the 89 patients, 36 (40.4%) were Responders to high-frequency rTMS. Binary logistic regression revealed that those with a cervical spinal cord injury and/or spasticity and women were more likely to respond to high-frequency rTMS.Conclusions:Female gender, cervical spinal cord injury, and spasticity are independent factors predicting rTMS efficacy in treating SCI, with spasticity demonstrating the strongest association.

ObjectiveTo elucidate the pharmacodynamic substances responsible for the anti-inflammatory and analgesic effects of Cyperi Rhizoma by structure-activity omics. MethodOn the basis of the previous in vitro efficacy study by our research group， this study explored the in vivo efficacy of the flavonoids in Cyperi Rhizoma. The flavonoids in Cyperi Rhizoma and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， PharmMapper， Swiss TargetPrediction， and available articles. The targets of the anti-inflammatory and analgesic effects were collected from DisGeNET and Online Mendelian Inheritance in Man （OMIM）. The common targets shared by flavonoids and the effects were selected as the direct targets of flavonoids endowing Cyperi Rhizoma with anti-inflammatory and analgesic effects， and protein-protein interaction （PPI） network of the core targets was constructed. The method of structure-activity omics was employed to correlate the structure and efficacy of one or more classes of chemical components in Cyperi Rhizoma with the targets as a bridge. The components were classified according to structure. Molecular docking of components to core targets was carried out via SYBYL-X 2.1.1， PyMol， and Discovery Studio 4.5 visualizer. Two targets with the highest binding affinity were selected to explore the relationship between compound structures and targets. ResultThe flavonoids in Cyperi Rhizoma exerted anti-inflammatory and analgesic effects on the mouse model of pain induced by formaldehyde. Eighteen components and 115 direct targets were screened out， and the core targets with high activities were protein kinase B1 （Akt1）， interleukin-1β （IL-1β）， cellular tumor antigen p53 （TP53）， prostaglandin-endoperoxide synthase 2 （PTGS2）， and matrix metalloproteinase-9 （MMP-9）. According to the structures， the flavonoids in Cyperi Rhizoma were classified into bioflavonoids， flavonols， flavones， and flavanes. The molecular docking results showed that flavonoids of Cyperi Rhizoma had the highest binding affinity to TP53 and PTGS2. The results of structure-activity omics showed that bioflavonoids represented the best binding structure to the targets， while their polyhydroxyl etherification resulted in a significant decrease in the binding affinity to PTGS2. Glycosides had higher binding affinity to PTGS2. The introduction of the long-chain hydrocarbon group to the A ring of flavonols facilitated the binding to TP53， while the change of B ring substituents was not the main factor affecting the binding affinity. The 3，4-dihydroxyl flavane outperformed 3-hydroxyl flavane in the binding to TP53， while the two compounds showed similar binding affinity to PTGS2. ConclusionThe method of structure-activity omics was used to analyze the material basis for the anti-inflammatory and analgesic effects of flavonoids in Cyperi Rhizoma. Structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.

Objective To investigate the effect of paeoniflorin on aerobic glycolysis of macrophages induced by resiquimod.Methods THP-1 cells were treated with phorbol ester(PM A)to differentiate into macrophages.The cells were divided into control group,model group and low,medium,high dose experimental group.The cells in the control group were cultured normally;in the model group,2 μg·mL-1 resiquimod was used to stimulate macrophages for 24 h to induce aerobic glycolysis.The low,medium and high dose experimental groups were treated with 1,10 and 100 μmol·L-1 paeoniflorin for 24 h on the basis of the model group.Cell activity was detected by cell counting kit-8(CCK-8)method.Lactate and glucose determination kit were used to detect lactate secretion and glucose consumption of cells in each group.The protein and mRNA expression levels of(PKM2)and(LDHA)were detected by Western blot and real-time fluorescence quantitative polynucleotide chain reaction(q-PCR)respectively.Immunofluorescence method was used to compare the fluorescence intensity of PKM2 in each group.Results After 24 h stimulation of THP-1 cells with 2 μg·mL-1 resiquimod,the glucose contents in cell culture supernatants of control group,model group and low,medium and high dose experimental groups were(14.70±0.44),(9.83±0.43),(10.68±0.29),(11.79±0.33)and(13.63±0.74)mmol·L-1;the lactate secreted by cells were(6.17±0.48),(11.94±0.55),(9.08±0.55),(7.79±0.66)and(6.50±0.55)mmol·L-1;the protein expression levels of PKM2 in cells were 1.00±0.00,1.33±0.18,1.02±0.17,0.74±0.17 and 0.73±0.18;the protein expression levels of LDHA were 1.00±0.00,1.20±0.09,0.90±0.14,0.76±0.12 and 0.78±0.17;the PKM2 mRNA levels were 1.00±0.09,2.11±0.23,1.98±0.31,1.38±0.25 and 0.93±0.32;the LDHA mRNA levels were 1.00±0.13,1.85±0.25,1.44±0.21,0.91±0.24 and 0.96±0.14;the average fluorescence intensities of PKM2 were 136.41±33.63,217.94±5.33,210.27±1.03,204.14±3.27 and 186.79±14.03.Compared with control group,the above indicators in model group showed statistically significant differences(P＜0.05,P＜0.01);compared with model group,the differences in the above indicators in medium and high dose experimental group were all statistically significant(P＜0.05,P＜0.01).Conclusion Paeoniflorin can inhibit the aerobic glycolysis of macrophages induced by resiquimod.

Objective To study the effects of Jinshui Liujun decoction(JLD)on airway inflammation and interferon-γ(IFN-γ)/interleukin-4(IL-4)imbalance in asthma.Methods The ovalbumin(OVA)was used to replicate the asthmatic mouse by injection and nebulization inhalation.Asthmatic mice were randomly divided into model group,positive control group(1.0 mg·kg-1 dexamethasone)and experimental-L,-M,-H groups(4.1,8.2 and 16.4 g·kg-1 JLD).The blank group and the model group were given purified water by gavage for 2 consecutive weeks.The lung function[tidal volume(TV)and respiratory rate(RR)]of mice was measured by lung function test system after administering JLD by gavage.IFN-γ,IL-4 in bronchoalveolar lavage fluid(BALF)and their genes in lung tissue were determined through enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction respectively.Results The TV levels in blank group,model group,positive control group and experimental-L,-M,-H groups were(118.90±24.20),(87.10±13.36),(112.70±18.92),(105.20±15.24),(107.60±16.47)and(110.10±17.41)μL;RR levels were(126.60±17.57),(178.80±31.06),(133.00±19.45),(146.00±25.82),(141.30±24.78)and(137.00±22.81)bpm;IFN-γ levels were(110.95±9.26),(60.16±2.75),(98.09±8.21)、(79.58±6.49)、(88.16±7.58)and(97.26±7.23)pg·mL-1;IL-4 levels were(118.06±8.47)、(416.08±22.21)、(272.17±13.14)、(319.34±15.27)、(298.77±14.83)and(278.71±14.24)pg·mL-1;the IFN-γ mRNA levels were 2.70±0.08,1.00±0.00,2.65±0.06,1.89±0.04,2.24±0.05 and 2.58±0.06;IL-4 mRNA levels were 0.25±0.02,1.00±0.00,0.26±0.02,0.61±0.05,0.50±0.03 and 0.33±0.03,respectively.There were statistically significant differences between the above indicators of model group and blank group,and experimental-L,-M,-H groups and model group(P＜0.05,P＜0.01).Conclusion JLD has a certain antiasthmatic effect and one of mechanisms is to alleviate the IFN-γ/IL-4 immune imbalance and inhibit airway inflammation.

OBJECTIVE: To investigate a new noninvasive diagnostic model for nonalcoholic fatty liver disease (NAFLD) based on features of tongue images. METHODS: Healthy controls and volunteers confirmed to have NAFLD by liver ultrasound were recruited from China-Japan Friendship Hospital between September 2018 and May 2019, then the anthropometric indexes and sampled tongue images were measured. The tongue images were labeled by features, based on a brief protocol, without knowing any other clinical data, after a series of corrections and data cleaning. The algorithm was trained on images using labels and several anthropometric indexes for inputs, utilizing machine learning technology. Finally, a logistic regression algorithm and a decision tree model were constructed as 2 diagnostic models for NAFLD. RESULTS: A total of 720 subjects were enrolled in this study, including 432 patients with NAFLD and 288 healthy volunteers. Of them, 482 were randomly allocated into the training set and 238 into the validation set. The diagnostic model based on logistic regression exhibited excellent performance: in validation set, it achieved an accuracy of 86.98%, sensitivity of 91.43%, and specificity of 80.61%; with an area under the curve (AUC) of 0.93 [95% confidence interval (CI) 0.68-0.98]. The decision tree model achieved an accuracy of 81.09%, sensitivity of 91.43%, and specificity of 66.33%; with an AUC of 0.89 (95% CI 0.66-0.92) in validation set. CONCLUSIONS The features of tongue images were associated with NAFLD. Both the 2 diagnostic models, which would be convenient, noninvasive, lightweight, rapid, and inexpensive technical references for early screening, can accurately distinguish NAFLD and are worth further study.
Humans ; Non-alcoholic Fatty Liver Disease/diagnostic imaging* ; Ultrasonography ; Anthropometry ; Algorithms ; China

ObjectiveTo identify the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Bupleuri Radix by structure-activity omics. MethodA mouse model of pain was established with formaldehyde to examine the anti-inflammatory and analgesic effects of saikosaponins in vivo. The core targets of the active components in Bupleurum Radix for the anti-inflammatory and analgesic effects were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Online Mendelian Inheritance in Man （OMIM）， and Search Tool for Recurring Instances of Neighbouring Genes （STRING）. The key core targets with high binding affinity were screened based on the comprehensive score in the molecular docking between different types of saikosaponins and core targets. The structure-activity relationship was discussed and analyzed based on the binding of compounds to pharmacodynamic targets. ResultSaikosaponins alleviated the foot swelling induced by formaldehyde and reduced the content of prostaglandin E₂ （PGE₂） in the mouse model， showcasing a significant inhibitory effect on the inflammatory pain caused by PGE₂. Nine components and 39 targets of saikosaponins， as well as 3 074 targets of anti-inflammatory and analgesic effects were screened out， and 22 common targets shared by saikosaponins and the effects were obtained as the direct targets. The protein-protein interaction （PPI） analysis showed that the main active components of Bupleurum Radix were saikosaponins a， b₁， b₂， b₃， c， d， e， f， and v， and the key targets were fms-related receptor tyrosine kinase 1 （FLT1）， kinase insert domain receptor （KDR）， fibroblast growth factor 2 （FGF2）， vascular endothelial growth factor A （VEGFA）， and signal transducer and activator of transcription 3 （STAT3）. Molecular docking between saikosaponins and the top 5 targets with high degrees in PPI network analysis revealed 25 highly active docks， including 6 docks with scores of 5-6 and 18 docks with scores above 6. ConclusionThis study adopted structural-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Bupleuri Radix in vivo， providing new ideas and methods for identifying the pharmacodynamic substances in traditional Chinese medicine.