ObjectiveThe present study aimed to investigate alterations in white matter microstructure and spontaneous neural activity in male college smokers, and to further explore their associations with nicotine dependence. Given that adolescence and early adulthood represent critical periods for brain maturation, particularly for white matter development, understanding the neural correlates of smoking behavior during this stage is of substantial importance for both neuroscience and public health. MethodsA total of 115 male undergraduate students were initially recruited for this study. After quality control and exclusion procedures, 52 male college smokers and 42 demographically matched healthy non-smokers were included in the final analysis. All participants underwent multimodal magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI). White matter fiber tracts were reconstructed using the automated fiber quantification (AFQ) method, which enables precise identification and quantification of major fiber bundles. Eighteen major white matter tracts were segmented for each participant. Along the core trajectory of each tract, 100 equidistant nodes were sampled. Fractional anisotropy (FA) was calculated at each node to assess white matter microstructural integrity, while amplitude of low-frequency fluctuation (ALFF) was computed to evaluate spontaneous neural activity within white matter tracts. Between-group differences in FA and ALFF were assessed using two-sample t-tests, with appropriate corrections applied for multiple comparisons. Furthermore, Pearson correlation analyses were conducted to examine the relationships between imaging-derived metrics (FA and ALFF values in regions showing significant group differences) and nicotine dependence severity, as measured by the Fagerström test for nicotine dependence (FTND). ResultsCompared with healthy non-smokers, male college smokers exhibited significantly increased FA values in several white matter tracts, including the left thalamic radiation, right corticospinal tract, forceps major of the corpus callosum, left uncinate fasciculus, and right arcuate fasciculus. These findings suggest altered microstructural organization or increased directional coherence within these pathways. In addition, smokers demonstrated significantly elevated ALFF values in the forceps major, right uncinate fasciculus, and left arcuate fasciculus, indicating enhanced spontaneous neural activity in these white matter regions. Correlation analyses revealed that FA values in the left thalamic radiation and right corticospinal tract were negatively correlated with FTND scores, suggesting that higher levels of nicotine dependence were associated with reduced microstructural integrity or altered fiber organization in these regions. In contrast, ALFF values in the forceps major and right uncinate fasciculus were positively correlated with FTND scores, indicating that greater nicotine dependence was associated with increased spontaneous neural activity in specific white matter pathways. ConclusionThe present study provides evidence that male college smokers exhibit distinct alterations in both white matter microstructure and functional activity. These abnormalities are not uniformly distributed but rather localized to specific fiber tracts implicated in sensorimotor processing, interhemispheric communication, and higher-order cognitive and emotional regulation. Importantly, the observed associations between imaging metrics and nicotine dependence severity suggest that these structural and functional alterations may reflect neurobiological mechanisms underlying addiction. The combination of AFQ-based tract profiling and multimodal MRI offers a sensitive approach for detecting subtle changes along white matter pathways, highlighting its potential utility in identifying neuroimaging biomarkers of nicotine dependence. Overall, these findings indicate that smoking during early adulthood may disrupt ongoing white matter maturation, potentially leading to long-term consequences for brain function. This study provides novel insights into the neural basis of nicotine dependence and underscores the importance of early intervention and prevention strategies targeting young smokers.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Foodborne illnesses caused by Salmonella pose significant threats to worldwide public health safety.In this study,a rapid method for screening viable Salmonella in oyster sauce and milk was developed by utilizing an electronic microbial growth analyzer(EMGA).Target food samples were diluted 10-fold with RVS broth and loaded into test tubes.Test tubes were positioned in the EMGA to determine the bacterial growth curves and the time required to reach the maximum growth rate(Tmgr).Using Salmonella typhimurium(S.typhimurium)asan model species,there was linear relationship between the logarithmic value of viable bacterial concentration(lgC)and Tmgr over the range of 5×101-5×106 CFU/mL,with a detection limit of 10 CFU/mL.For oyster sauce,the regression equation was Tmgr(min)=-80.775lg[C/(CFU/mL)]+754.96(R2=0.9907),and the recovery rates of S.typhimurium ranged from 95.2%to 119.8%,with relative standard deviations(RSD)ranging from 3.5%to 16.3%.For milk,the regression equation was Tmgr(min)=-71.922 lg[C/(CFU/mL)]+618.65(R2=0.9985),with recovery rates ranging from 98.4%to 110.6%and RSD ranging from 6.4%to 12.8%.The EMGA method required only one portable instrument,and involving only three manual steps,i.e.,dilution,transfer,and insertion.When S.typhimurium contamination reached 106 CFU/mL,the total time consumption,from the unwrapping of samples to the readout of bacterial concentration,was no more than 7 h.When applied to detection of actual oyster sauce and milk samples,the new method demonstrated strong consistency with plate counting results in positive detection rates.This method was superior to the plate counting method,which was generally considered as a gold standard,in terms of accuracy,precision,simplicity and efficiency,representing a promising alternative for the on-site screening and quantification of viable Salmonella in oyster sauce and milk products.

Objective:To analyze the infiltration of immune cells in different molecular subtypes of endometrial cancer(EC)at the protein level and explore the correlation between immune infiltration and clinicopathological features.Methods:Clinical data from 75 mismatch repair-deficient(MMR-D)EC cases and 74 mismatch re-pair-proficient(MMR-P)EC cases with comparable differentiation levels,diagnosed at Sichuan Provincial People's Hospital between January 2013 and January 2021,were selected.Molecular classification of EC was con-ducted according to the ProMisE standard.Immunohistochemistry(IHC)staining and fluorescent multiplexed im-munohistochemistry(F-mIHC)techniques were used to quantify the distribution of CD8+T cells,regulatory T cells(Tregs),and macrophages.The clinicopathological features and immune infiltration characteristics of different subtypes were investigated.Results:Among 149 samples,75 were MMR-D,8 were POLE-mutated(POLEmut),13 were p53-mutated(p53abn),and 53 were p53 wild-type(p53wt).The infiltration characteristics of CD8+T cells,Tregs,and macrophages were no statistically significant differences correlated with age and pathological stage(P>0.05).Among the molecular subtypes of EC,MMR-D tumors demonstrated a significantly higher densi-ty of CD8+T cells and Tregs compared to MMR-P tumors(P<0.05).Further comparison across the four EC mo-lecular subtypes revealed that the MMR-D subtype,which had a favorable prognosis,displayed a significantly high density of CD8+T cells compared to the p53abn subtype and the p53wt subtype(P<0.05).Additionally,the Tregs density of the MMR-D tumors was significantly higher than that of the p53wt tumors,in both the tumor area(P<0.05)and the stroma area(P<0.05).The POLEmut type tumors,which had the best prognosis,showed a high infiltration of CD8+T cells and Tregs cells compared to the p53abn and p53wt types,although there was no signifi-cant statistical difference(P>0.05).The p53wt subtype,which had a moderate prognosis,exhibited low density of CD8+T cells(P<0.05)and Tregs(tumor area,P<0.01,stroma area,P<0.05)compared to MMR-D tumors.The p53abn subtype,which was associated with the worst prognosis,exhibited higher infiltration of M2-like macro-phages than the MMR-D subtype(P<0.05)and the p53wt subtype(P<0.05)in tumor region,and lower CD8+T cell density than the MMR-D subtype(P<0.05).No significant statistical difference was observed in the density of M1-like macrophages across the four molecular subtypes in either the tumor or stroma areae(P>0.05).Conclu-sions:There was no statistically significant relation found between infiltration characteristics of immune cells and clinicopathological features.The types and distribution of infiltrated immune cells were different across these EC molecular subtypes.This indicated that ECs with different molecular subtype exhibited different features of immune infiltration which is closely associated with patient prognosis.

Objective To investigate the risk factors of hemodynamic instability after carotid artery stenting by meta-analysis.Methods Ten databases were searched:PubMed,ProQuest,ScienceDirect,Embase,Cochrane Library,Web of Science,China Knowledge Network,Wanfang Data,VIP Information Database,and China Biomedical Database.The search date was from inception until 2 February 2024,and meta-analysis was performed using Stata 16.0 statistical software.Results A total of 27 studies with 4199 subjects and 22 influencing factors were included.The studies showed a 37.4％(95％CI 30.3％-44.8％)incidence of haemodynamic instability after carotid stenting,Meta-analysis determined that age＞60 years(P＜0.001),hypertension(P＜0.001),calcified plaque(P＜0.001),stenosis＞70％(P=0.008),eccentric plaque(P=0.002),distance from the largest stenosis to the carotid bifurcation≤ 10 mm(P＜0.001),stenosis involvement of the balloon or bifurcation(P＜0.001),balloon post-dilation(P=0.003),open-loop stenting(P＜0.001),dilated balloon diameter≥5 mm(P=0.002),repeat balloon dilation(P=0.011)and balloon dilation pressure≥8 atm(P＜0.001)are risk factors for intraoperative and postoperative haemodynamic instability in patients undergoing carotid artery stenting surgery.Statin use was a protective factor(P＜0.001).Conclusions Medical staff working in the clinic should assess the patient's condition preoperatively,identify risk factors that may lead to haemodynamic instability,and avoid unnecessary intraoperative stimulation of patients who are already in a high-risk state.Reduce postoperative clinical complications in patients with carotid artery stenosis and improve patient recovery.

Aim To investigate the effect of PU.1 in-hibitor DB2313 on lupus nephritis in MRL/lpr mice and its mechanism.Methods Thirty female MRL/lpr mice were randomly divided into the model group,DB2313 group and TACI-Ig group,with 10 mice in each group.Another 10 female BALB/c mice were se-lected as normal control groups.Mice in the DB2313 group received intraperitoneal DB2313 injections every two days,and those in the TACI-Ig group received subcutaneous injections of TACI-Ig every two days.Mice in the control group and model group were intra-gastrically given the same amount of 0.9％NaCl injec-tion every day.Before the drug intervention and for 1 to 5 weeks after the intervention,the urine of mice was collected regularly,the urine protein content was meas-ured,and the renal damage index was evaluated.The histopathological changes of kidney were observed by HE,Masson and PAS staining.The expression levels of immune complex of C3 in kidney tissue were detec-ted by immunohistochemistry.The concentrations of u-rea nitrogen(BUN),serum creatinine(Scr),inter-leukin-6(IL-6),and tumor necrosis factor alpha(TNF-α)in the serum samples were assayed utilizing the respective kits.The expression levels of PU.1 and FLT3 in kidney tissues were determined by immunoflu-orescence technology,and the protein expressions of PU.1,FLT3,PI3K,AKT and phosphorylated AKT(p-AKT)in kidney tissues were detected by Western blot.Results DB2313 treatment significantly allevia-ted the pathological damage of kidney in MRL/lpr mice,and reduced the deposition of C3,kidney injury index and 24-hour urine protein in renal tissue.The results of ELISA showed that DB2313 administration could significantly reduce the serum levels of BUN,Scr,IL-6 and TNF-α in MRL/lpr mice.The results of immunofluorescence and Western blot further showed that DB2313 treatment could significantly down-regu-late the protein expression of PU.1,PI3K and p-AKT,and up-regulate the protein expression of FLT3.Con-clusion DB2313 has an ameliorating effect on lupus nephritis in MRL/lpr mice,and its underlying mecha-nism may involve the inhibition of the transcription fac-tor PU.1-mediated signaling pathway.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Early-life stress (ES) leads to cognitive dysfunction in female adolescents, but the underlying neural mechanisms remain elusive. Recent evidence suggests that the cell adhesion molecules NECTIN1 and NECTIN3 play a role in cognition and ES-related cognitive deficits in male rodents. In this study, we aimed to investigate whether and how nectins contribute to ES-induced cognitive dysfunction in female adolescents. Applying the well-established limited bedding and nesting material paradigm, we found that ES impairs recognition memory, suppresses prefrontal NECTIN1 and hippocampal NECTIN3 expression, and upregulates corticotropin-releasing hormone (Crh) and its receptor 1 (Crhr1) mRNA levels in the hippocampus of adolescent female mice. Genetic experiments revealed that the reduction of dorsal CA1 (dCA1) NECTIN3 mediates ES-induced object recognition memory deficits, as knocking down dCA1 NECTIN3 impaired animals' performance in the novel object recognition task, while overexpression of dCA1 NECTIN3 successfully reversed the ES-induced deficits. Notably, prefrontal NECTIN1 knockdown did not result in significant cognitive impairments. Furthermore, acute systemic administration of antalarmin, a CRHR1 antagonist, upregulated hippocampal NECTIN3 levels and rescued object and spatial memory deficits in stressed mice. Our findings underscore the critical role of dCA1 NECTIN3 in mediating ES-induced object recognition memory deficits in adolescent female mice, highlighting it as a potential therapeutic target for stress-related psychiatric disorders in women.
Animals ; Female ; Mice ; CA1 Region, Hippocampal/metabolism* ; Cell Adhesion Molecules/metabolism* ; CRF Receptor, Type 1/metabolism* ; Memory Disorders/etiology* ; Mice, Inbred C57BL ; Nectins/genetics* ; Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors* ; Recognition, Psychology/physiology* ; Stress, Psychological/complications*

OBJECTIVE: This study investigated the antidepression mechanisms of Xiaoyaosan (XYS), a classic Chinese prescription, from the perspective of energy metabolism in the brain and intestinal tissues. METHODS: Chronic unpredictable mild stress model-a classic depression rat model-was established. Effects of XYS on behaviors and gastrointestinal motility of depressed rats were investigated. Effects of XYS on energetic charge (EC), adenosine triphosphate-related enzymes, and key enzymes of energy metabolism in both hippocampus and jejunum tissues of depressed rats were investigated using high-performance liquid chromatography, biochemical analysis, and real-time quantitative polymerase chain reaction, respectively. Spearman correlation analysis was conducted to construct a correlation network of "behavior-brain energy metabolism-intestinal energy metabolism" of depression. RESULTS: XYS significantly reduced the abnormal behaviors that observed in depressed rats and increased the EC and the activity of Na⁺-K⁺-adenosine triphosphatase (ATPase) and Ca²⁺-Mg²⁺-ATPase in hippocampus and jejunum tissues of depressed rats. XYS restored the key energetic pathways that had been interrupted by depression, including glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, XYS exhibited antidepressive effects in terms of regulating energy metabolism in tissues of both brain and intestine. CONCLUSION XYS significantly corrected the disturbances in EC and energy metabolism-related enzymes of both brain and intestinal tissues, alleviating both core and concomitant symptoms of depression. The current findings underscore the role of energy metabolism in the antidepressive activity of XYS, providing a fresh perspective on depression, and novel research strategies for revealing the mechanism of actions of traditional Chinese medicines on multi-site and multi-symptom diseases. Please cite this article as: Xiao MT, Wang SY, Wu XL, Zhao ZY, Wang HM, Liu HM, Qin XM, Liu XJ. Antidepressant mechanism of Xiaoyaosan: A perspective from energy metabolism of the brain and intestine. J Integr Med. 2025; 23(6):706-720.
Animals ; Energy Metabolism/drug effects* ; Antidepressive Agents/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Brain/drug effects* ; Male ; Depression/metabolism* ; Rats ; Rats, Sprague-Dawley ; Intestines/drug effects* ; Hippocampus/drug effects*