ObjectiveTobacco-related diseases remain one of the leading preventable public health challenges worldwide and are among the primary causes of premature death. In recent years, accumulating evidence has supported the classification of nicotine addiction as a chronic brain disease, profoundly affecting both brain structure and function. Despite the urgency, effective diagnostic methods for smoking addiction remain lacking, posing significant challenges for early intervention and treatment. To address this issue and gain deeper insights into the neural mechanisms underlying nicotine dependence, this study proposes a novel graph neural network framework, termed TI-GNN. This model leverages functional magnetic resonance imaging (fMRI) data to identify complex and subtle abnormalities in brain connectivity patterns associated with smoking addiction. MethodsThe study utilizes fMRI data to construct functional connectivity matrices that represent interaction patterns among brain regions. These matrices are interpreted as graphs, where brain regions are nodes and the strength of functional connectivity between them serves as edges. The proposed TI-GNN model integrates a Transformer module to effectively capture global interactions across the entire brain network, enabling a comprehensive understanding of high-level connectivity patterns. Additionally, a spatial attention mechanism is employed to selectively focus on informative inter-regional connections while filtering out irrelevant or noisy features. This design enhances the model’s ability to learn meaningful neural representations crucial for classification tasks. A key innovation of TI-GNN lies in its built-in causal interpretation module, which aims to infer directional and potentially causal relationships among brain regions. This not only improves predictive performance but also enhances model interpretability—an essential attribute for clinical applications. The identification of causal links provides valuable insights into the neuropathological basis of addiction and contributes to the development of biologically plausible and trustworthy diagnostic tools. ResultsExperimental results demonstrate that the TI-GNN model achieves superior classification performance on the smoking addiction dataset, outperforming several state-of-the-art baseline models. Specifically, TI-GNN attains an accuracy of 0.91, an F1-score of 0.91, and a Matthews correlation coefficient (MCC) of 0.83, indicating strong robustness and reliability. Beyond performance metrics, TI-GNN identifies critical abnormal connectivity patterns in several brain regions implicated in addiction. Notably, it highlights dysregulations in the amygdala and the anterior cingulate cortex, consistent with prior clinical and neuroimaging findings. These regions are well known for their roles in emotional regulation, reward processing, and impulse control—functions that are frequently disrupted in nicotine dependence. ConclusionThe TI-GNN framework offers a powerful and interpretable tool for the objective diagnosis of smoking addiction. By integrating advanced graph learning techniques with causal inference capabilities, the model not only achieves high diagnostic accuracy but also elucidates the neurobiological underpinnings of addiction. The identification of specific abnormal brain networks and their causal interactions deepens our understanding of addiction pathophysiology and lays the groundwork for developing targeted intervention strategies and personalized treatment approaches in the future.

Objective To analyze the application effect of cisatracurium besilate assisted mechanical ventilation in patients with moderate to severe acute respiratory distress syndrome(ARDS)and the impact on prognosis.Methods Patients with moderate to severe ARDS were divided into the control group and the treatment group according to different treatment methods using cohort method.The control group was treated with mechanical ventilation in prone position.The treatment group was treated with cisatracurium besilate(0.15 mg·kg-1)assisted mechanical ventilation in prone position.The duration of mechanical ventilation,weaning time,total length of hospital stay,ventilator-related parameters[arterial partial pressure of oxygen(PaO2),oxygenation index(OI)and central venous pressure(CVP)],the Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)scores,Sequential Organ Failure Assessment Scale(SOFA)scores,inflammatory factors[interleukin-6(IL-6),interleukin-8(IL-8)and tumor necrosis factor-α(TNF-α)],short-term mortality and the incidence of complications were compared between the groups.Results The treatment group and the control group included 39 and 41 cases,respectively.The offline duration for the treatment group and the control group were(15.11±1.97)and(12.01±1.62)days,with statistically significant differences(P＜0.05).Three days after mechanical ventilation,the PaO2 for the treatment group and the control group were(88.24±9.05)and(80.01±8.34)mmHg;OI were(219.87±22.01)and(170.86±18.53)mmHg·％-1;IL-6 was(18.04±1.92)and(26.23±3.04)ng·mL-1,respectively.After treatment,the APACHE Ⅱ scores for the treatment group and the control group were(16.05±1.74)and(20.05±1.08)points;the SOFA scores were(5.04±0.66)and(7.23±1.05)points.The mortality rates within 90 days after discharge for the treatment group and the control group were 2.56％and 19.51％,and the overall complication rates were 7.69％and 29.27％.Statistically significant differences were observed in the comparison of the above indicators between the treatment group and the control group(all P＜0.05).The death rate of the treatment group within 90 days after discharge(2.56％)was significantly lower than that of the control group(19.51％,P＜0.05),and the total complication rate(7.69％)was significantly lower than that of the control group(29.27％,P＜0.05).Conclusion Cisatracurium besilate assisted mechanical ventilation in prone position has a definite application effect in patients with moderate to severe ARDS,and can effectively improve the prognosis.

Objective To observe the effects of matrine on the proliferation,migration,and invasion of human neuroblastoma cells,and to investigate its potential mechanism.Methods This study was divided into AS experimental group(SK-N-AS cells treated with IC50 concentration of matrine),AS blank group(SK-N-AS cells cultured under normal conditions),AS control group(SK-N-AS cells treated with an equal amount of dimethyl sulfoxide),DZ experimental group(SK-N-DZ cells treated with IC50 concentration of matrine),DZ blank group(SK-N-DZ cells cultured under normal conditions),and DZ control group(SK-N-DZ cells treated with an equal amount of dimethyl sulfoxide).Scratch assay and Transwell chamber were used to measure the effect of matrine on the migration and invasion.The expression of E-cadherin,N-cadherin and Vimentin were tested by Western blot.Results After different intervention,the migration percentages of AS blank group,AS control group,AS experimental group,DZ blank group,DZ control group and DZ experimental group were(66.32±3.12)％,(65.27±3.44)％,(23.73±0.79)％,(46.25±4.68)％,(44.15±5.60)％and(16.77±3.52)％,respectively;the number of invasive cells were 870.45±19.32,865.32±23.39,492.74±16.81,1 198.10±43.71,1 203.03±71.91 and 891.69±42.62,respectively;the expression levels of E-cadherin protein were(100.00±11.72)％,(105.65±13.11)％,(477.20±29.71)％,(100.00±12.54)％,(97.78±12.77)％and(240.53±12.23)％,respectively;the expression levels of N-cadherin protein were(100.00±15.44)％,(103.90±10.76)％,(43.52±9.96)％,(100.00±10.12)％,(104.95±10.49)％and(38.39±8.70)％,respectively;Vimentin protein expression levels were(100.00±9.51)％,(97.39±11.33)％,(59.13±10.25)％,(100.00±13.20)％,(96.27±11.01)％and(47.67±9.48)％,respectively.There were statistically significant differences in the above indexes between the AS group and the AS blank group(P＜0.01,P＜0.001),and there were statistically significant differences between the above indexes in the DZ group and the DZ blank group(P＜0.01,P＜0.001).Conclusion Matrine inhibits the proliferation,migration,and invasion of neuroblastoma SK-N-AS and SK-N-DZ cells,potentially through suppressing epithelial-mesenchymal transition.

Objective To evaluate the pharmacokinetics(PK)of tenofovir alafenamide Fumarate tablets(25 mg)in healthy Chinese subjects after single oral administration to provide a basis for bioequivalence evaluation.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design under fasting condition,while three-way crossover design under fed condition,42 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test product(T)or reference product(R)25 mg.Plasma concentration of tenofovir alafenamide and tenofovir were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by WinNonlin software(8.1 version)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The test product and the reference product under fasting study,the main PK parameters of tenofovir alafenamide were as follows:Cmax were(215.17±94.24)and(199.30±71.11)ng·mL-1;AUC0-t were(135.44±71.60)and(123.91±53.82)h·ng·mL-1;the main PK parameters of tenofovir were as follows:Cmax were(7.30±2.27)and(7.12±1.74)ng·mL-1,AUC0-t of tenofovir were(237.16±47.09)and(230.06±43.41)h·ng·mL-1,respectively.The test product and the reference product under fed study,the main PK parameters of tenofovir were as follows:Cmax were(197.69±82.19)and(197.10±110.54)ng·mL-1;AUC0-t were(197.69±82.19)and(197.10±110.54)h·ng·mL-1;the main PK parameters of tenofovir were as follows:CMax were(2.57±1.37)and(2.58±1.31)ng·mL-1;AUC0-t were(227.08±74.33)and(238.51±128.30)h·ng·mL-1,respectively.The 90％confidence interval for geometric mean ratio of Cmax,AUC0-tof T and R under fed condition were between 80.00％-125.00％,respectively.The incidence of adverse events in fasting and fed tests was 21.43％and 30.95％,respectively,and no serious adverse event was reported.Conclusion The test formulation and reference formulation of tenofovir alafenamide fumarate tablets were equivalent and was safe.

Objective To investigate the therapeutic effect and mechanism of Jianwei Xiaozhang Tablets on rats with precancerous lesions of gastric cancer(PLGC).Methods Forty male SD rats were randomly divided into the normal group,the model group,the folic acid group and the Jianwei Xiaozhang Tablets group,with 10 rats in each group.In addition to the normal group,the other three groups of rats were prepared by gavage with Ranitidine Aqueous Solution combined with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)solution drinking method for the preparation of PLGC model.After successful modeling,drugs were administered accordingly for 7 weeks.The changes in body mass of rats during modeling and drug administration were recorded,the gross view of the stomach was observed and scored pathologically,the coefficients of spleen and liver were determined,the pathological changes in gastric tissue were observed by hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA)was used to measure serum gastrin(GAS),motilin(MTL)and glucagon(GC),Alisin Blue-Periodic Acid Schiff's(AB-PAS)staining was used to observe the thickness of the mucosal layer of gastric tissues,the expressions of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),and endothelial-type nitric oxide synthase(eNOS)proteins in gastric tissues were detected by protein immunoblotting(Western Blot),and the expression of vascular endothelial growth factor A(VEGFA)protein in gastric tissues was detected by immunofluorescence staining.Results Compared with the normal group,the body mass of rats in the model group grew slowly during the experimental period,gastric macroscopic pathological scores were significantly increased(P＜0.01),splenic coefficient and hepatic coefficient were significantly decreased(P＜0.01),the gastric tissues showed cuprocyte hyperplasia and intestinal chemotaxis,gastric tissues'inflammation scores were significantly increased(P＜0.01),the serum GAS content was significantly increased(P＜0.01),and the MTL,GC contents were significantly reduced(P＜0.05),and the thickness of the mucous membrane layer of gastric tissue was significantly reduced(P＜0.05),the protein expression levels of PI3K,p-PI3K,Akt,p-Akt and eNOS were reduced(P＜0.01),and the protein expression level of VEGFA was reduced(P＜0.01);compared with the model group,the above indexes of the Jianwei Xiaozhang Tablets group and the folic acid group were all significantly improved(P＜0.05 or P＜0.01),among which,the Jianwei Xiaozhang Tablets group had a better improvement effect in the proliferation of cup cells and intestinal chemotaxis in gastric tissues,the content of serum GAS,and the thickness of the mucous layer in gastric tissues.Conclusion The mechanism of the improvement of PLGC in rats by Jianwei Xiaozhang Tablets may be related to the activation of the PI3K-Akt-eNOS pathway,which in turn promotes the angiogenesis and repair of gastric damaged tissues.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

Objective To explore the role of pulmonary surfactant(PS)combined with budesonide in improving oxygenation and clinical outcomes of neonatal acute respiratory distress syndrome(ARDS).Methods The present study is a historically controlled trial.Infants with ARDS requiring mechanical ventilation and PS replacement therapy were collected from the neonatal unit of Southwest Medical University.Those from January 2022 to November 2022 were set as intervention group(PS+ budesonid,n=35),treated with intratracheal instillation of a mixed suspension of budesonide(0.25 mg/kg)and PS(200 mg/kg),and continuous budesonide nebulization(0.25 mg/kg,twice per day)until withdrawal,then compared with a historical cohort,who just received intratracheal instillation of PS(200 mg/kg)(January 2020-December 2021,PS group,n=35).Baseline data such as gender,mode of delivery,1 min and 5 min Apgar score,birth weight,gestational age,time of onset,and cause of onset were recorded in both groups.The oxygenation and clinical outcomes of infants were compared between the two groups,including:(1)Arterial blood gas analysis indicators,such as partial pressure of oxygen(PaO2)and oxygenation index(OI)before treatment and at 6,12 and 24 hours of treatment;(2)Clinical observation and evaluation indicators,such as the time to withdrawal,duration of oxygen supplementation,length of stay,improvement of the radiological images of the lungs at 72 h of treatment,and repeated PS use;(3)Blood chemistry indicators,such as white blood cell(WBC),neutrocyte(NEU),procalcitonin(PCT)before treatment and at 3 and 7 days of treatment;and(4)Observation indicators of complications,weight growth,and mortality outcomes,such as the incidences of intracranial hemorrhage,gastrointestinal hemorrhage,neonatal necrotizing enterocolitis(NEC),and hyperglycemia,weight growth,and fatality rate.Results The differences in baseline data between the two groups were not statistically different(P＞0.05).The levels of PaO2 of the two groups were increased after treatment for different time periods,while the levels of OI were decreased(P＜0.001),and the levels of above indexes changed more significantly in PS+budesonide group than those in PS group(P＜0.05).The time to withdrawal,duration of oxygen supplementation,and length of stay in PS+budesonide group were shorter than those in PS group;the radiological images of the lungs showed that the pulmonary inflammation absorption was significantly better in PS+ budesonide group than that in PS group,while no significant difference between the two groups of infants with repeated PS use.The NEU was significantly higher in PS+budesonide group than in PS group at 3 d and 7 d of treatment(P＜0.001);and at 3 days of treatment,the PCT levels were significantly lower in PS+budesonide group than that in PS group(P＜0.05).The incidences of intracranial hemorrhage,gastrointestinal hemorrhage,NEC,hyperglycemia,weight growth,and fatality rate were not significantly different between the two groups(P＞0.05).Conclusion The use of budesonide in addition to surfactant may improve the oxygenation of neonates with ARDS,improve the inflammatory infiltrates in lungs,shorten the duration of mechanical ventilation and oxygen supplementation,and without short-term complications associated with budesonide use.

Objective:To summarize the imaging features of severe unilateral transverse sinus and sigmoid sinus thromboses, and evaluate the efficacy and safety of intravascular interventional therapy in them.Methods:Thirty-seven patients with severe unilateral transverse sinus and sigmoid sinus thromboses clinically mainly manifested as intracranial hypertension and accepted endovascular intervention in Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from June 2012 to September 2022 were chosen; their clinical data were retrospectively analyzed and imaging features were summarized. Short-term efficacy was evaluated according to blood flow restoration degrees and pressure gradient reduction in the occlusive sinus and modified neurological symptoms before and after endovascular intervention. Hospitalized complications were observed; safety and long-term efficacy were evaluated according to postoperative clinical follow-up and imaging results 6-12 months after endovascular intervention.Results:(1) Preoperative brain MRI and (or) CT showed different degrees of swelling of the brain tissues, with the affected side as the target; mixed signals/density shadow could be seen in the blocked transverse sinus and sigmoid sinus; venous cerebral infarction or post-infarction cerebral hemorrhage could be combined in some patients. MRV, CTV and DSA showed poor or completely occluded transverse sinus and sigmoid sinus while normal in the contralateral side; obvious thrombus filling-defect was observed in the occluded venous sinus after mechanical thrombolysis. (2) Occlusive sinus blood flow was restored in all patients after endovascular intervention, and pressure gradient of the occlusive segment decreased from (16.6±3.3) mmHg before to (2.8±0.8) mmHg after endovascular intervention. Before discharge, clinical symptoms of all patients were significantly improved (modified Rankin scale [mRS] scores of 0 in 30 patients, 1 in 5 patients, 2 in 1 patient and 3 in 1 patient), and 2 patients had unilateral limb movement disorder (muscle strength grading III and IV, respectively). All patients received clinical follow-up for (9.6±3.0) months. At the last follow-up, neurological function obviously improved compared with that before endovascular intervention, without new neurosystem-related symptoms (mRS scores of 0 in 30 patients, 1 in 6, and 2 in 1 patient). In 34 patients received MRV or DSA follow-up, 28 had complete recanalization of occlusive sinus and 6 had partial recanalization, without obvious stenosis or recurrent occlusion.Conclusions:Severe unilateral transverse sinus and sigmoid sinus thrombosis can cause local intracranial venous blood stasis, and then cause "increased regional venous sinus pressure", which is manifested as unilateral brain tissue swelling and even venous cerebral infarction or post-infarction cerebral hemorrhage. Early diagnosis and endovascular intervention can obviously improve the prognosis of these patients, enjoying good safety.

Aim To evaluate the hypolipidemic effect of the total phenylpropanoid glycosides extracted from Ligustrum robustum (Roxb.) Blume (LRTPG) on hyperlipidemic golden hamsters and explore its regulatory effect on intestinal flora. Methods Sixty hamsters were randomly divided into a control group, a model group, a positive drug group, LRTPG-L group, LRTPG-M group, and LRTPG-H group. After the successful induction of the model by high-fat diet, the animals were continuously administered for four weeks, and their blood lipids and liver lipids were detected. The formed feces from the colorectal region of the hamsters in the control group, model group and LRTPG-H group were collected for 16S rDNA sequencing. Results LRTPG reduced serum TG, TC, LDL-C and liver TG, TC concentrations significantly in hyperlipidemic hamsters. The results of the intestinal microbiota sequencing showed that compared to the control group, LRTPG significantly decreased the relative abundance of the phylum Firmicutes and increased the relative abundance of the phylum Bacteroidetes and Verrucomicrobia (P < 0.01) at the phylum level. At the family level, LRTPG significantly increased the relative abundance of Christensenellaceae, Peptococcaceae, and Verrucomicrobiaceae (P < 0.05 or P < 0.01). At the genus level, LRTPG significantly increased the relative abundance of Oscillospira, Oscillibacter, Flavonifractor and Akkermansiaceae (P < 0.05 or P < 0.01). These changes in the flora were beneficial to the hypolipidemic effect of LRTPG. Conclusion LRTPG may exert its hypolipidemic effect by improving the intestinal flora disorder caused by a high-fat diet in golden hamsters.

Histone deacetylases(HDACs)can deacetylate histones,leading to tighter DNA binding,and thereby playing a role in inhibiting gene transcription.On the contrary,histone deacetylase inhibitors(HDACis)can promote chromatin relaxation,enabling various transcription factors to bind specifically to DNA and activate transcription genes.Dental stem cells(DSCs)are human adult stem cells.These cells have the characteristics of less damage and low immune rejection during sampling,and are especially important seed cells in the process of osteogenesis,odontogenesis and other differentiation.A large number of experimental studies have shown that HDACs and HDACis together play important roles in cell division and differentiation,signal transduction,regulation of cellular inflammation and other life processes.This review summarizes the research progress of HDACs and HDACis in regulating osteogenic and odontogenic differentiation of DSCs,aiming to provide insights into the study of the interaction between HDACs and HDACis,and potentially guide clinical application of DSCs in the treatment of tooth and bone injury.