ObjectiveBased on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， to identify the in vivo and in vitro chemical components of total phenolic acids in Gei Herba（TPAGH）， and to clarify the pharmacological effects and potential mechanisms of the effective part in promoting acute wound healing and inhibiting scar formation. MethodsUPLC-Q-Orbitrap-MS was used to identify the chemical components of TPAGH and ingredients absorbed in vivo after topical administration. A total of 120 ICR mice were randomly divided into the model group， recombinant human epidermal growth factor（rhEGF） group（4 mg·kg^-1）， and low， medium， and high dose groups of TPAGH（3.5， 7， 14 mg·kg^-1）， with 24 mice in each group. A full-thickness skin excision model was constructed， and each administration group was coated with the drug at the wound site， and the model group was treated with an equal volume of normal saline， the treatment was continued for 30 days， during which 8 mice from each group were sacrificed on days 6， 12， and 30. The healing of the wounds in the mice was observed， and histopathological changes in the skin tissues were dynamically observed by hematoxylin-eosin（HE）， Masson， and Sirius red staining， and enzyme-linked immunosorbent assay（ELISA） was used to dynamically measure the contents of interleukin-6（IL-6）， tumor necrosis factor-α（TNF-α）， vascular endothelial growth factor A（VEGFA）， matrix metalloproteinase（MMP）-3 and MMP-9 in skin tissues. Network pharmacology was used to predict the targets related to the promotion of acute wound healing and the inhibition of scar formation by TPAGH， and molecular docking of key components and targets was performed. Gene Ontology（GO） biological process analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were carried out for the related targets， so as to construct a network diagram of herbal material-compound-target-pathway-pharmacological effect-disease for further exploring its potential mechanisms. ResultsA total of 146 compounds were identified in TPAGH， including 28 phenylpropanoids， 31 tannins， 23 triterpenes， 49 flavonoids， and 15 others， and 16 prototype components were found in the serum of mice. Pharmacodynamic results showed that， compared with the model group， the TPAGH groups showed a significant increase in relative wound healing rate and relative scar inhibition rate（P<0.05）， and the number of new capillaries， number of fibroblasts， number of new skin appendages， epidermal regeneration rate， collagen deposition ratio， and Ⅲ/Ⅰ collagen ratio in the tissue were significantly improved（P<0.05， 0.01）， the levels of IL-6， TNF-α， MMP-3 and MMP-9 in the skin tissues were reduced to different degrees， while the level of VEGFA was increased. Network pharmacology analysis screened 10 core targets， including tumor protein 53（TP53）， sarcoma receptor coactivator（SRC）， protein kinase B（Akt）1， signal transducer and activator of transcription 3（STAT3）， epidermal growth factor receptor（EGFR） and so on， participating in 75 signaling pathways such as advanced glycation end-products（AGE）-receptor for AGE（AGE/RAGE） signaling pathway， phosphatidylinositol 3-kinase（PI3K）/Akt signaling pathway， mitogen-activated protein kinase（MAPK） signaling pathway. Molecular docking confirmed that the key components genistein， geraniin， and casuariin had good binding ability to TP53， SRC， Akt1， STAT3 and EGFR. ConclusionThis study comprehensively reflects the chemical composition of TPAGH and the absorbed components after topical administration through UPLC-Q-Orbitrap-MS. TPAGH significantly regulates key indicators of skin healing and tissue reconstruction， thereby clarifying its role in promoting acute wound healing and inhibiting scar formation. By combining in vitro and in vivo component identification with network pharmacology， the study explores how key components may bind to targets such as TP53， Akt1 and EGFR， exerting therapeutic effects through related pathways such as immune inflammation and vascular regeneration.

Objective To investigate the association between depression and autonomic nervous function in Parkinson disease （PD）， and to provide a basis for clinical treatment. Methods Clinical and neurocirculation data were collected from 168 PD patients who attended Department of Neurology， The Second Affiliated Hospital of Hainan Medical College， from July 2022 to July 2023， and according to the score of Beck Depression Inventory， the patients were divided into depression in PD （dPD） group with 57 patients and non-dPD （nPD） group with 111 patients. General clinical data were collected from all patients. The supine-to-standing TCD test was performed for all patients to record systolic blood pressure （SBP）， diastolic blood pressure （DBP）， heart rate （HR）， and the mean velocity （Vm）， pulsatility index （PI）， and resistance index （RI） of the middle cerebral artery （MCA） at 1， 3， and 5 minutes in both the supine and standing positions. A network was constructed for depression symptoms in PD. Results In the network of non-motor symptoms in PD， depression showed the highest centrality and the strongest predictability and was strongly correlated with sleep/fatigue and mood/cognition， with a strength centrality stability coefficient （CS strength） of 0.440. Compared with the nPD group， the dPD group had significantly lower supine HR， ∆HR， Vm in the standing position， and ∆Vm%， a significantly greater ∆DBP， and a significantly higher proportion of patients with dizziness with orthostatic hypotension or orthostatic cerebral hypoperfusion （P<0.05）. Depression was positively correlated with ∆SBP， ∆DBP， Vm in the supine position， and RI in the standing position， and it was negatively correlated with ∆HR， DBP in the supine position， HR in the supine position， and ∆PI （CS strength=0.375 and 0.222）. Conclusion Impairment of cardiovascular and cerebral autonomic nervous function might be involved in the pathogenesis of depression in PD， and intervention of depression can help improve the overall non-motor symptoms of PD， with sleep， fatigue， and cognition as the effective targets for improving depression in PD.
Parkinson Disease ; Depression

Objective To evaluate the pharmacokinetics characteristics of single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects.Methods This was a single-center,randomized,double-blind,placebo-controlled study.Twelve healthy adult Chinese subjects were randomized to receive single-dose of Etripamil nasal spray 70 mg(n=10)or placebo nasal spray(n=2).Blood and urine samples were collected prior and post dose.Etripamil in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters were calculated by WinNonlin non-compartmental model.Results Following the single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects,the peak concentration of Etripamil in plasma was quickly attained,with a Cmax of(66.76±56.61)ng·mL-1 and a median(range)tmax of 4.00(3.00-5.00)min.The plasma concentrations of Etripamil had fallen approximately 65％from peak value at 25 min after dosing,and close to 80％within 50 min.The AUC0-last and AUC0-∞ were(3 104.16±2 654.46)and(4 048.77±2 682.38)ng·min·mL-1,respectively.The urine excretion percentage of Etripamil during 24 h was(0.01±0.01)％.Among the 12 subjects who were treated with Etripamil or placebo,10 subjects reported a total of 29 treatment-emergent adverse events(TEAEs).All of the TEAEs were mild in severity.The most common TEAEs were rhinorrhoea and lacrimation increased.Conclusion Etripamil was quickly absorbed after intranasal administration,followed by rapid distribution and elimination(not primarily excreted by renal);Etripamil 70 mg was safe and well tolerated by the healthy Chinese adult subjects.

Objective To investigate the application value of spectral computed tomography venography(CTV)in the display and staging of deep venous thrombosis(DVT)in the lower extremity.Methods Eighty-two patients with CTV were selected and ran-domly divided into group A(42 patients)and group B(40 patients).Group A:tube voltage 120 kVp.Group B:gemstone spectral ima-ging(GSI)mode,reconstruction of 50 keV and iodine(water)maps.The CT and standard deviation(SD)values of the veins were measured,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated in 120 kVp images of group A and in 50 keV images of group B.Two observers scored the image quality of the 2 groups subjectively,and Kappa test was used to examine the con-sistency.Based on the duration from the occurrence of clinical symptoms,the DVTs were classified.The CT values and iodine con-centration(IC)of DVT were measured in the 120 kVp images of group A and in the iodine(water)maps of group B,respectively.The receiver operating characteristic(ROC)curve was drawn to compare the effectiveness of CT values and IC in diagnosing DVT staging.Results CT values,SNR,and CNR of veins in group B were higher than those in group A(P<0.05).The subjective scores of the two groups were consistent(Kappa=0.926-0.955,P<0.05).The score for the display of veins and thrombus clarity in group B was 5(4,5),which was better than the score of 4(3,4)in group A(P<0.05).The efficiency of IC in diagnosing DVT staging[area under the curve(AUC)=0.973]was better than that of CT values(AUC=0.891).Conclusion The spectral CTV can improve the contrast of lower extremity deep veins and the clarity of thrombus,and can provide more objective indicators for the diagnosis of thrombus staging,which is conducive to accurate clinical diagnosis and treatment.

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

ObjectiveGastric cancer (GC) seriously affects human health and life, and research has shown that it is closely related to the serine/glycine metabolism. The proliferation ability of tumor cells is greatly influenced by the metabolism of serine and glycine. The aim of this study was to investigate the molecular mechanism of serine/glycine metabolism can affect the proliferation of gastric cancer cells. MethodsIn this work, a stable metabolic dynamic model of gastric cancer cells was established via a large-scale metabolic network dynamic modeling method in terms of a potential landscape description of stochastic and non-gradient systems. Based on the regulation of the model, a quantitative analysis was conducted to investigate the dynamic mechanism of serine/glycine metabolism affecting the proliferation of gastric cancer cells. We introduced random noise to the kinetic equations of the general metabolic network, and applied stochastic kinetic decomposition to obtain the Lyapunov function of the metabolic network parameter space. A stable metabolic network was achieved by further reducing the change in the Lyapunov function tied to the stochastic fluctuations. ResultsDespite the unavailability of a large number of dynamic parameters, we were able to successfully construct a dynamic model for the metabolic network in gastric cancer cells. When extracellular serine is available, the model preferentially consumes serine. In addition, when the conversion rate of glycine to serine increases, the model significantly upregulates the steady-state fluxes of S-adenosylmethionine (SAM) and S-adenosyl homocysteine (SAH). ConclusionIn this paper, we provide evidence supporting the preferential uptake of serine by gastric cancer cells and the important role of serine/glycine conversion rate in SAM generation, which may affect the proliferation ability of gastric cancer cells by regulating the cellular methylation process. This provides a new idea and direction for targeted cancer therapy based on serine/glycine metabolism.

Aim To analyze the anti-A549 and HI299 lung ade-nocarcinoma activities via using examples of baicalin, astragalo-side, hesperidin and cisplatin based on real time cellular analysis (RTCA) technology, and to build a new strategy for EC50 e-valuation reflecting the time-dimensional characteristic. Methods Using RTCA Software Pro for data analysis and GraphPad Prism and Origin Pro plotting, the in vitro anti-A549 and H1299 lung adenocarcinoma activities of baicalin, astragaloside, hesperidin, and cisplatin were characterized using the endpoint method and time dimension, respectively. Results (X) There were significant differences in EC50 values of A549 and H1299 cells at 24 h and 48 h endpoint methods. (2) The correlation coefficient of the curve fitted with the four-parameter equation was > 0. 9, and the dynamic change of EC50 remained relatively stable (the linear fitting of EC50 at adjacent 4 points I slope 1^1) used to calculate the EC50 value within this time dimension. The EC50 of baicalin, astragaloside, hesperidin and cisplatin on A549 cells was 52. 97 ±1.75 плпо! • L~1(16~48 h) , 62.88 ± 2.91 ijunol • L"1 (32.25 -48 h) , 78.84 ±0.33 плпо1 • L"1 (21.5 -29.75 h), 13.57 ±1.54 плпо1 • L_1(27.5 -48 h), respectively; the EC50 of baicalin, astragaloside, hesperidin and cisplatin on H1299 cells was 43. 71 ± 1. 26 |лто1 • L_1 ( 19. 5 -48 h), 47.23 ±1. 19 |лто1 • L_1(14 -48 h) , 39.45 ±0.24 плпо1 • L"1 (12.75 -46.25 h), 25.97 ±4.76 плпо1 • L"1 (10. 25 -48 h) , respectively. The results showed that the time window for the anti-tumor effect of the test solution/drug was different. Conclusions Based on RTCA technology, it is more accurate and reasonable to select EC50 data that exhibit better fitting, stable changes, and time-dimensional characteristics for the evaluation of anti-tumor activity. In addition, this method of distinguishing different effective time of antitumor drugs can provide a reference for the timing of clinical combination drugs, and this approach will also provide a reference for further related studies.

ObjectiveTo explore the relationships between internet gaming disorder (IGD), interpersonal needs, loneliness, and depression in adolescents through the construction of a chain mediation model, to clarify the underlying mechanisms of these associations, and to provid a theoretical basis for depression prevention and intervention. MethodsBased on the data of the 7th Population Census, using convenient sampling method 1 106 adolescents aged between 10‒19 years in South China (176), North China (147), Central China (332), and East China (451) were selected to conduct a cross-sectional survey, with a ratio of 1∶1∶1.5∶2.5. The survey was conducted with a questionnaire consisting of general information (sex, age, grade, parents’ education level), the Chinese version of the IGDS9-SF, the INQ-15, the short-form of the ULS-8 and the PHQ-9 were used to evaluate the depression status of adolescents. Spearman correlation analysis was used to explore the correlation between the variables. A multiple-mediator model was constructed using IBM SPSS Statistics 22.0 PROCESS to examine the mediating effects of interpersonal needs and loneliness on the relationship between IGD and depression. The significance of the chain mediating effect was tested using the Bootstrap method. ResultsOverall, 39.06% (432/1 106) adolescents experienced depression. The incidence of depression among adolescents with smoking and without smoking was 62.50% and 38.36%, respectively. Similarly, the incidence of depression among adolescents with alcohol consuming and without alcohol consuming was 61.94% and 35.94%, respectively. There were statistically significant differences between IGD, interpersonal needs, loneliness, and depression (P<0.01). The chain mediation model demonstrated a good fit, and the bootstrap test showed that the 95%CI of each mediation path did not include 0, indicating significant mediation effects. The overall effect was 0.337. The direct effect of IGD on depression was significant (effect value=0.138, 95%CI:0.102-0.173, P<0.001). The mediation effects included three paths: ① IGD →interpersonal needs → depression (effect value=0.073, P<0.05), accounting for 21.47% of the total effect;② IGD→ loneliness → depression (effect value=0.093, P<0.05), accounting for 27.35%; and ③ IGD → interpersonal needs → loneliness → depression (effect value=0.036, P<0.05), accounting for 10.59%. ConclusionInterpersonal needs and loneliness independently and jointly mediate the relationship between IGD and depression among adolescents. To reduce depression and improve mental health in this population, measures should be taken to prevent and intervene in IGD, address adolescents’ social and emotional needs, enhance satisfaction of interpersonal needs, and reduce loneliness.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.