ObjectiveThe controllability changes of structural brain network were explored based on the control and brain network theory in young smokers, this may reveal that the controllability indicators can serve as a powerful factor to predict the sleep status in young smokers. MethodsFifty young smokers and 51 healthy controls from Inner Mongolia University of Science and Technology were enrolled. Diffusion tensor imaging (DTI) was used to construct structural brain network based on fractional anisotropy (FA) weight matrix. According to the control and brain network theory, the average controllability and the modal controllability were calculated. Two-sample t-test was used to compare the differences between the groups and Pearson correlation analysis to examine the correlation between significant average controllability and modal controllability with Fagerström Test of Nicotine Dependence (FTND) in young smokers. The nodes with the controllability score in the top 10% were selected as the super-controllers. Finally, we used BP neural network to predict the Pittsburgh Sleep Quality Index (PSQI) in young smokers. ResultsThe average controllability of dorsolateral superior frontal gyrus, supplementary motor area, lenticular nucleus putamen, and lenticular nucleus pallidum, and the modal controllability of orbital inferior frontal gyrus, supplementary motor area, gyrus rectus, and posterior cingulate gyrus in the young smokers’ group, were all significantly different from those of the healthy controls group (P<0.05). The average controllability of the right supplementary motor area (SMA.R) in the young smokers group was positively correlated with FTND (r=0.393 0, P=0.004 8), while modal controllability was negatively correlated with FTND (r=-0.330 1, P=0.019 2). ConclusionThe controllability of structural brain network in young smokers is abnormal. which may serve as an indicator to predict sleep condition. It may provide the imaging evidence for evaluating the cognitive function impairment in young smokers.

Alzheimer’s disease (AD), a progressive neurodegenerative disorder and the leading cause of dementia in the elderly, is characterized by severe cognitive decline, loss of daily living abilities, and neuropsychiatric symptoms. This condition imposes a substantial burden on patients, families, and society. Despite extensive research efforts, the complex pathogenesis of AD, particularly the early mechanisms underlying cognitive dysfunction, remains incompletely understood, posing significant challenges for timely diagnosis and effective therapeutic intervention. Among the various cellular components implicated in AD, GABAergic interneurons have emerged as critical players in the pathological cascade, playing a pivotal role in maintaining neural network integrity and function in key brain regions affected by the disease. GABAergic interneurons represent a heterogeneous population of inhibitory neurons essential for sustaining neural network homeostasis. They achieve this by precisely modulating rhythmic oscillatory activity (e.g., theta and gamma oscillations), which are crucial for cognitive processes such as learning and memory. These interneurons synthesize and release the inhibitory neurotransmitter GABA, exerting potent control over excitatory pyramidal neurons through intricate local circuits. Their primary mechanism involves synaptic inhibition, thereby modulating the excitability and synchrony of neural populations. Emerging evidence highlights the significant involvement of GABAergic interneuron dysfunction in AD pathogenesis. Contrary to earlier assumptions of their resistance to the disease, specific subtypes exhibit vulnerability or altered function early in the disease process. Critically, this impairment is not merely a consequence but appears to be a key driver of network hyperexcitability, a hallmark feature of AD models and potentially a core mechanism underlying cognitive deficits. For instance, parvalbumin-positive (PV⁺) interneurons display biphasic alterations in activity. Both suppressing early hyperactivity or enhancing late activity can rescue cognitive deficits, underscoring their causal role. Somatostatin-positive (SST⁺) neurons are highly sensitive to amyloid β-protein (Aβ) dysfunction. Their functional impairment drives AD progression via a dual pathway: compensatory hyperexcitability promotes Aβ generation, while released SST-14 forms toxic oligomers with Aβ, collectively accelerating neuronal loss and amyloid deposition, forming a vicious cycle. Vasoactive intestinal peptide-positive (VIP⁺) neurons, although potentially spared in number early in the disease, exhibit altered firing properties (e.g., broader spikes, lower frequency), contributing to network dysfunction (e.g., in CA1). Furthermore, VIP release induced by 40 Hz sensory stimulation (GENUS) enhances glymphatic clearance of Aβ, demonstrating a direct link between VIP neuron function and modulation of amyloid pathology. Given their central role in network stability and their demonstrable dysfunction in AD, GABAergic interneurons represent promising therapeutic targets. Current research primarily explores three approaches: increasing interneuron numbers (e.g., improving cortical PV⁺ interneuron counts and behavior in APP/PS1 mice with the antidepressant citalopram; transplanting stem cells differentiated into functional GABAergic neurons to enhance cognition), enhancing neuronal activity (e.g., using low-dose levetiracetam or targeted activation of specific molecules to boost PV⁺ interneuron excitability, restoring neural network γ‑oscillations and memory; non-invasive neuromodulation techniques like 40 Hz repetitive transcranial magnetic stimulation (rTMS), GENUS, and minimally invasive electroacupuncture to improve inhibitory regulation, promote memory, and reduce Aβ), and direct GABA system intervention (clinical and animal studies reveal reduced GABA levels in AD-affected brain regions; early GABA supplementation improves cognition in APP/PS1 mice, suggesting a therapeutic time window). Collectively, these findings establish GABAergic interneuron intervention as a foundational rationale and distinct pathway for AD therapy. In conclusion, GABAergic interneurons, particularly the PV⁺, SST⁺, and VIP⁺ subtypes, play critical and subtype-specific roles in the initiation and progression of AD pathology. Their dysfunction significantly contributes to network hyperexcitability, oscillatory deficits, and cognitive decline. Understanding the heterogeneity in their vulnerability and response mechanisms provides crucial insights into AD pathogenesis. Targeting these interneurons through pharmacological, neuromodulatory, or cellular approaches offers promising avenues for developing novel, potentially disease-modifying therapies.

Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the mod-ulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theo-retically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(p-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electro-phoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while pre-senting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

AIM To study endophytic fungi from Scutellaria baicalensis Georgi.and the enzyme inhibitory activities of their secondary metabolites.METHODS Six different media were used to isolate and purify endophytic fungi from S.baicalensis by tissue homogenate method.The activities of secondary metabolites were evaluated by targeting different enzymes.The highly active strains were identified by molecular biology combined with morphology,and the highly active chemical components were tracked and separated by modern chromatographic separation technology.RESULTS Sixty-four endophytic fungal strains were isolated from S.baicalensis,and one hundred and twenty-eight secondary metabolites were obtained by fermentation.The samples with certain inhibitory activities against adenosine deaminase(ADA),β-lactamase and tyrosinase(TYR)accounted for 14.06%,3.91%and 18.75%,respectively.Strain HTS-23-2 showed high TYR inhibitory activity,and 99%homology with Aspergillus flavus by molecular identification.One compound was isolated from the fermentation samples and identified as kojic acid.CONCLUSION S.baicalensis harbors a rich diversity of endophytic fungi,which serve as a valuable resource for active substances.

Objective: To investigate the efficacy of humanized anti-CD25 monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: A total of 64 patients with SR-aGVHD between June 2019 and October 2020 in Suchow Hopes Hematology Hospital were enrolled in this study. Humanized anti-CD25 monoclonal antibodies 1 mg·kg(-1)·d(-1) were administered on days 1, 3, and 8, and then once per week according to the disease progression. Efficacy was assessed at days 7, 14, and 28 after humanized anti-CD 25 treatment. Results: Of the 64 patients with a median age of 31 (15-63) years, 38 (59.4%) were male and 26 (40.6%) were female. The overall response (OR) rate of the humanized CD25 monoclonal antibody in 64 patients with SR-aGVHD on days 7, 14, and 28 were 48.4% (31/64), 53.1% (34/64), and 79.7% (51/64), respectively. Liver involvement is an independent risk factor for poor efficacy of humanized CD25 monoclonal antibody for SR-aGVHD at day 28 (OR=9.588, 95% CI 0.004-0.291, P=0.002). The median follow-up time for all patients was 17.1 (0.2-50.8) months from the start of humanized CD25 monoclonal antibody therapy. The 1- and 2-year OS rates were 63.2% (95% CI 57.1% -69.3%) and 52.6% (95% CI 46.1% -59.1%), respectively. The 1- and 2-year DFS rates were 58.4% (95% CI 52.1% -64.7%) and 49.8% (95% CI 43.4% -56.2%), respectively. The 1- and 2-year NRM rates were 28.8% (95% CI 23.1% -34.5%) and 32.9% (95% CI 26.8% -39.0%), respectively. The results of the multifactorial analysis showed that liver involvement (OR=0.308, 95% CI 0.108-0.876, P=0.027) and GVHD grade Ⅲ/Ⅳ (OR=9.438, 95% CI 1.211-73.577, P=0.032) were independent risk factors for OS. Conclusion: Humanized CD25 monoclonal antibody has good efficacy and safety for SR-aGVHD. This study shows that SR-aGVHD with pretreatment grade Ⅲ/Ⅳ GVHD and GVHD involving the liver has poor efficacy and prognosis and requires early intervention.
Adult ; Female ; Humans ; Male ; Middle Aged ; Acute Disease ; Antibodies, Monoclonal/therapeutic use* ; Graft vs Host Disease/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Retrospective Studies ; Salvage Therapy/methods* ; Steroids ; Adolescent ; Young Adult

Inner Mongolia autonomous region of China and Mongolia are the primary regions where Chinese and Mongolian medicine and its medicinal plant resources are distributed. In this study, 133 families, 586 genera, and 1 497 species of medicinal plants in Inner Mongolia as well as 62 families, 261 genera, and 467 species of medicinal plants in Mongolia were collected through field investigation, specimen collection and identification, and literature research. And the species, geographic distribution, and influencing factors of the above medicinal plants were analyzed. The results revealed that there were more plant species utilized for medicinal reasons in Inner Mongolia than in Mongolia. Hotspots emerged in Hulunbuir, Chifeng, and Tongliao of Inner Mongolia, while there were several hotspots in Eastern province, Sukhbaatar province, Gobi Altai province, Bayankhongor province, Middle Gobi province, Kobdo province, South Gobi province, and Central province of Mongolia. The interplay of elevation and climate made a non-significant overall contribution to the diversity of plant types in Inner Mongolia and Mongolia. The contribution of each factor increased significantly when the vegetation types of Inner Mongolia and Mongolia were broadly divided into forest, grassland and desert. Thus, the distribution of medicinal plant resources and vegetation cover were jointly influenced by a variety of natural factors such as topography, climate and interactions between species, and these factors contributed to and constrained each other. This study provided reference for sustainable development and rational exploitation of medicinal plant resources in future.
Humans ; Plants, Medicinal ; Mongolia ; Climate ; Medicine, Mongolian Traditional ; China

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid β oxidation in the liver.
Rats ; Male ; Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Sterol Regulatory Element Binding Protein 1/metabolism* ; Diet, High-Fat/adverse effects* ; Diosgenin/metabolism* ; Chaperonin 60/therapeutic use* ; Rats, Sprague-Dawley ; Liver ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Triglycerides ; RNA, Messenger/metabolism* ; Simvastatin/therapeutic use* ; Body Weight ; Lipid Metabolism ; Mammals/metabolism*

Enzymes are closely associated with the onset and progression of numerous diseases, making enzymes a primary target in innovative drug development. However, the challenge remains in identifying compounds that exhibit potent inhibitory effects on the target enzymes. With the continuous expansion of the total number of natural products and increasing difficulty in isolating and enriching new compounds, traditional high-throughput screening methods are finding it increasingly challenging to meet the demands of new drug development. Virtual screening, characterized by its high efficiency and low cost, has gradually become an indispensable technology in drug development. It represents a prominent example of the integration of artificial intelligence with biopharmaceuticals and is an inevitable trend in the rapid development of innovative drug screening in the future. Therefore, this article primarily focused on systematically reviewing the recent applications of virtual screening technology in the development of enzyme inhibitors and explored the prospects and advantages of using this technology in developing new drugs, aiming to provide essential theoretical insights and references for the application of related technologies in the field of new drug development.
Artificial Intelligence ; Enzyme Inhibitors/pharmacology* ; High-Throughput Screening Assays ; Molecular Docking Simulation

OBJECTIVE: To investigate the optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) requiring complex percutaneous coronary intervention (PCI). METHODS: A total of 2403 patients with DM who underwent complex PCI from January to December 2013 were consecutively enrolled in this observational cohort study and divided according to DAPT duration into a standard group (11-13 months, n = 689) and two prolonged groups (13-24 months, n = 1133; > 24 months, n = 581). RESULTS: Baseline characteristics, angiographic findings, and complexity of PCI were comparable regardless of DAPT duration. The incidence of major adverse cardiac and cerebrovascular event was lower when DAPT was 13-24 months than when it was 11-13 months or > 24 months (4.6% vs. 8.1% vs. 6.0%, P = 0.008), as was the incidence of all-cause death (1.9% vs. 4.6% vs. 2.2%, P = 0.002) and cardiac death (1.0% vs. 3.0% vs. 1.2%, P = 0.002). After adjustment for confounders, DAPT for 13-24 months was associated with a lower risk of major adverse cardiac and cerebrovascular event [hazard ratio (HR) = 0.544, 95% CI: 0.373-0.795] and all-cause death (HR = 0.605, 95% CI: 0.387-0.944). DAPT for > 24 months was associated with a lower risk of all-cause death (HR = 0.681, 95% CI: 0.493-0.942) and cardiac death (HR = 0.620, 95% CI: 0.403-0.952). The risk of major bleeding was not increased by prolonging DAPT to 13-24 months (HR = 1.356, 95% CI: 0.766-2.401) or > 24 months (HR = 0.967, 95% CI: 0.682-1.371). CONCLUSIONS For patients with DM undergoing complex PCI, prolonging DAPT might improve the long-term prognosis by reducing the risk of adverse ischemic events without increasing the bleeding risk.

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.