Background In 2021, chronic obstructive pulmonary disease (COPD) emerged as the forth leading cause of death in the world. However, the impact of air pollutants on COPD is still inconsistent across current studies. Objective To analyze the relationship between ambient sulfur dioxide (SO₂) exposure and hospital admissions for COPD in Lanzhou, and to examine the modified effects of SO₂ across different genders, age groups, and seasons. Methods A total of 20718 hospital admission records for COPD were collected from Lanzhou between 2016 and 2020, alongside synchronized data on SO₂ concentration and meteorological variables. A generalized additive model integrated with a distributed lag nonlinear model was used to assess the relationship and the lag effects between SO₂ exposure and COPD admissions. Potential confounders, including meteorological factors, day-of-the-week effect, and holidays, were controlled for, with a maximum lag period set at 7 d. Two-pollutant models and sensitivity analyses were conducted to ensure robustness. Results are expressed as relative risks (RR) with 95% confidence intervals (95%CI). Results During the study period, the average daily number of COPD admissions was 11.34±7.03. The average mass concentration of SO₂ was (23.72±12.35) μg·m⁻³. SO₂ exposure was positively correlated with COPD admissions; specifically, each 10 μg·m⁻³ increase in SO₂ concentration was associated with an RR of 1.440 (95%CI: 1.317, 1.573). Stratified analyses found that at a cumulative lag of 7 d, the RRs were higher among females, individuals aged ≥65 years, and during the cold season. Conversely, no significant increase in COPD admission risk related to SO₂ was observed during the warm season. For every 10 μg·m⁻³ increase in SO₂ concentration, the RR was 1.483 (95%CI: 1.311, 1.678) for females, 1.441 (95%CI: 1.311, 1.583) for those aged > 65 years， and 1.595 (95%CI: 1.313, 1.937) during the cold season. Conclusion Short-term exposure to ambient SO₂ exposure in Lanzhou is associated with an increased risk of COPD admission. The association is more pronounced among females, the elderly (aged> 65 years) and during the cold season.

Exportin 1 (XPO1) is aberrantly overexpressed in various malignant tumors and can lead to the loss of anti-tumor effects of important tumor suppressor proteins such as p53, RB1, and FOXO by mediating their nuclear export. Although XPO1 inhibitor Selinexor has entered clinical application, its single-agent anti-tumor activity remains suboptimal, which is closely related to the compensatory activation of multiple signaling pathways in response to XPO1 inhibition. Focusing on the core regulatory role of XPO1 in tumor cells, this article systematically summarizes the current landscape of combination therapies involving XPO1 inhibitors and various targeted agents, including inhibitors of CDK4/6, FLT3, BET, ATR, and BCL2/MDM2, aiming to provide some reference for the development of XPO1-centered combination therapy strategies.

Neoadjuvant therapy has become the standard treatment for locally advanced resectable esophageal cancer, significantly improving long-term survival compared to surgery alone. Neoadjuvant therapy has evolved to include various strategies, such as concurrent chemoradiotherapy, chemotherapy, immunotherapy, or targeted combination therapy. This enriches clinical treatment options and provides a more personalized and scientific treatment approach for patients. This article aims to comprehensively summarize current academic research hot topics, review the rationale and evaluation measures of neoadjuvant therapy, discuss challenges in restaging methods after neoadjuvant therapy, and identify the advantages and disadvantages of various neoadjuvant therapeutic strategies.

Objective To establish and evaluate an integrated disease-syndrome rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Methods Thirty male Wistar rats were allocated randomly into three groups(n=10 per group):sham operation(sham),2-vessel occlusion(2-VO)group,and sleep deprivation combined with 2-VO(SD+2-VO)group.We comprehensively assessed Qi deficiency and blood stasis syndrome manifestations in the rats using a dual evaluation approach,combining exhaustive swimming tests with quantitative tongue chroma analysis.Cognitive function was evaluated using the Barnes maze,and cerebral blood flow was compared using laser speckle contrast imaging.The histopathology of the hippocampal cytoarchitecture and white matter were examined using hematoxylin-eosin(HE)and Luxol fast blue(LFB)staining,respectively,and ultrastructural alterations of neurons in the hippocampal CA1 region were observed by transmission electron microscopy(TEM).Protein expression levels of NeuN,vascular endothelial growth factor A(VEGFA)and CD31 were detected by Western Blot and immunofluorescence.Results Cerebral blood flow was significantly reduced in rats in the 2-VO group compared with the sham group,but they failed to recapitulate the key clinical hallmarks of Qi deficiency and blood stasis syndrome.In contrast,rats in the SD+2-VO group exhibited significantly reduced locomotor activity,exacerbated cerebral hypoperfusion,shortened swimming duration,and darkened tongue color compared with 2-VO rats.Rats in the SD+2-VO group demonstrated significantly impaired learning and memory abilities in the Barnes maze test.Consistent with these observations,HE staining,TEM,and LFB staining revealed substantial neuronal and white matter damage in the SD+2-VO group.NeuN expression was decreased and VEGFA and CD31 expression levels were increased in the 2-VO and SD+2-VO groups,as shown by Western Blot.Taken together,these findings indicated that the SD+2-VO model effectively recapitulated the clinical features of chronic cerebral ischemia with Qi deficiency and blood stasis pattern.Conclusions The combination of sleep deprivation and bilateral carotid artery occlusion successfully established a rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Compared with the 2-VO model,SD+2-VO model demonstrates more pronounced syndrome manifestations and better clinical relevance,thus providing a valuable animal model for traditional Chinese medicine research on chronic cerebral ischemia.

The Song,Jin,and Yuan dynasties marked a period of transformation in traditional Chinese medicine for visceral syn-drome differentiation,with the emergence of numerous new ideas and theories.Zhang Yuansu was a key figure in the transition from Han and Tang to Jin and Yuan medicine.His Medication Patterns for Treating Deficiency-Excess and Cold-Heat of Five Viscera embod-ies his thinking on visceral syndrome differentiation.This work breaks away from the pre-Song classification of visceral syndrome differ-entiation based on deficiency and excess,focusing on the specific physiological and pathological patterns of the five zang organs and proposing corresponding treatments for their specific syndromes.Medication Patterns propose the diagnosis and treatment of reproductive system diseases based on the Mingmen,assuming that the Mingmen undertakes some of the functions of the kidneys.This enriched the connotations of visceral syndrome differentiation and provided an important theoretical basis for identifying certain complex pathogenesis.The visceral syndrome differentiation concept in the Medication Patterns has promoted subsequent research on visceral syndrome differentiation,exemplified by works such as Li Dongyuan's"Treatise on the Spleen and Stomach",Zhu Danxi's"Treatise on the Xianghuo"and the"Mingmen Theory".In-depth exploration of the inherent differentiation logic and theoretical framework of the Medication Patterns is of great significance to current research on differentiation standards and norms.

Objective To evaluate the efficacy and safety of polyethylene glycol electrolyte powder(PEG)combined with linaclotide(Lin)for bowel preparation in elderly constipated patients before colonoscopy.Methods In this prospective,randomized controlled trial,90 elderly patients with constipation undergoing colonoscopy were recruited at our hospital from June 2022 to December 2023.Participants were randomly assigned to three groups(n=30 each):PEG-3L alone,PEG-3L+Lin,and PEG-2L+Lin.Primary outcome was Boston Bowel Preparation Scale(BBPS)score and secondary outcomes included adverse event rates,colonoscopy completion rate,withdrawal time,and polyp detection rate.Statistical analysis was performed using independent t-tests and chi-square tests.Results The PEG-3L+Lin group achieved significantly higher BBPS scores than both PEG-3L alone and PEG-2L+Lin groups did(both P<0.001).The PEG-2L+Lin group also outperformed the PEG-3L alone group in cleansing efficacy(90.0%vs.76.7%,P=0.008).The PEG-2L+Lin group demonstrated the best tolerability and lowest adverse event rate,the PEG-3L group had the longest withdrawal time(P<0.05),but the three groups showed no significant difference in polyp detection rates.Conclusion PEG combined with linaclotide significantly improves bowel cleansing in elderly constipated patients.PEG-2L+Lin regimen provides optimal balance between efficacy,safety,and tolerability,making it a preferable choice for this population.

Objective To investigate the effects of aerobic exercise and different exercise habits on skeletal muscle function and the possible molecular mechanisms in colorectal cancer-loaded mice.Methods Thirty-five 5-week-old BABL/c male mice were acclimatized to feeding for 1 week and then divided randomly into the following groups:control(D),tumor(M),exercise preconditioning(QAM),lifetime exercise(AM),and exercise(HAM)groups(n=7 mice per group).Mice in the QAM and AM groups underwent aerobic exercise regimen 1 from weeks 2～6.At week 7,mice in the experimental groups received 0.2 mL of CT26 colon cancer cell suspension subcutaneously in the dorsal aspect of the left hind limb,while control mice received 0.2 mL of saline at the corresponding site.Mice in the AM and HAM groups were subjected to aerobic exercise regimen 2 for weeks 7～9.The general status and skeletal muscle mass and function were monitored in all mice throughout the experiments.After completion of the experiment,samples were collected and the cross-sectional area of gastrocnemius muscle fibers(CSA)was measured by hematoxylin and eosin staining and expression levels of proteins related to synthesis and catabolism of the gastrocnemius muscle were analyzed by Western Blot.Results(1)The weight ratio of the gastrocnemius muscle was significantly lower in mice in the M,QAM,and HAM groups compared with group D,and was significantly higher in AM mice compared with M,QAM,and HAM mice.(2)Grip strength,endurance,skeletal muscle circumference,and CSA were significantly lower in group D mice compared with the other groups,and was most enhanced in group HAM.Endurance and CSA were consistently enhanced in groups QAM,AM,and HAM.(3)Muscle RING-finger protein-1(MuRF1)expression levels were significantly lower in groups M,QAM,AM,and HAM than in group D,significantly lower in groups AM and HAM than in group M,and significantly lower in group HAM than in group QAM.(4)Fibronectin type Ⅲ domain-containing protein 5(FNDC5)expression levels were significantly lower in group M than in groups D and QAM.(5)Peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression levels were significantly lower in the QAM and HAM groups compared with group M.(6)Expression levels of phospho(p)-AMP-activated protein kinase(AMPK)/AMPK and p-AMPK were significantly higher in group QAM than in groups D and M,p-AMPK expression significantly lower in groups AM and HAM was than in group QAM,and AMPK expression was significantly lower in groups QAM,AM,and HAM than in group D.Conclusions Exercise preconditioning and continuous aerobic exercise can improve skeletal muscle mass and function in CT26 colon cancer-loaded mice by activating AMPK phosphorylation to stimulate skeletal muscle secretion of FNDC5,thereby regulating the expression of MuRF1 protein.

Objective:To explore the chain mediating effect of self-esteem and emotional resilience on the relationship between cyberbullying and depression of college students.Methods:From March to October 2023, a total of 346 college students were measured using Chinese version of Delaware bullying victimization scale-student, self esteem scale, adolescents' emotional resilience questionnaire, and patient health questionnaire-9, adopting a longitudinal tracking design with a total of 2 sessions and a 6-month interval between each session. SPSS 25.0 software was used for common method bias, descriptive statistical analysis, correlation analysis and mediating effect test.Results:(1) The results showed that cyberbullying T1 (4.54±1.60) was significantly and negatively correlated with self-esteem T2 (27.85±4.43) ( r=-0.152, P<0.01), while not significantly correlated with emotional resilience T2 (40.50±9.55) ( r=-0.093, P>0.05).Self-esteem T2 was significantly and positively correlated with emotional resilience T2( r=0.583, P<0.01), while negatively correlated with depression T2 ( r=-0.425, P<0.01). Emotional resilience T2 was significantly and negatively correlated with depression T2 ( r=-0.479, P<0.01).(2) Self-esteem and emotional resilience fully mediated the relationship between cyberbullying and depression. The mediating effect was consisted of two pathways including mediating effect of self-esteem and the chain mediating effect of self-esteem and emotional resilience, with effect value of 0.024 and 0.021 respectively. Conclusion:Cyberbullying can indirectly affect depression through the mediation of self-esteem and chain mediating effect of self-esteem and emotional resilience.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

AIM:To explore the causal association between the counts of five types of white blood cells—neutrophils,monocytes,eosinophils,baso-phils,and lymphocytes—and venous thromboem-bolism(VTE).METHODS:Mendelian randomization(MR)analysis method was used,with genetic vari-ants associated with the five types of white blood cells as instrumental variables,and venous throm-boembolism occurrence risk as the outcome vari-able,inverse variance-weighted(IVW)method was employed as the primary analysis method,with MR-Egger regression,weighted median(WM),sim-ple model,and weighted mode methods used as supplements,to analyze the causal association be-tween the counts of five types of white blood cells and VTE,followed by reverse MR analysis.RE-SULTS:Neutrophil and lymphocyte counts are caus-ally associated with the risk of VTE.For neutrophil count,the IVW estimate(OR=0.867,95%CI:0.761-0.981,P=0.031),MR-Egger estimate(OR=0.754,95%CI:0.571-0.996,P=0.048),weighted median es-timate(OR=0.846,95%CI:0.729-0.981,P=0.027),and weighted model estimate(OR=0.748,95%CI:0.595-0.942,P=0.014)were calculated.For lympho-cyte count,the IVW estimate(OR=0.838,95%CI:0.741-0.949,P=0.005)and weighted median esti-mate(OR=0.024,95%CI:0.718-0.977,P=0.024)were calculated.Reverse MR analysis showed a causal association between the risk of VTE and neu-trophil count,the IVW estimate(OR=0.989,95%CI:0.980-0.999,P=0.024).CONCLUSION:Neutrophil and lymphocyte counts are related to the risk of VTE,and decrease in neutrophil and lymphocyte numbers may increase the risk of VTE.VTE occur-rence risk is associated with neutrophil count,and reducing the risk of VTE occurrence may increase neutrophil count.Further research is needed to un-derstand the underlying biological mechanisms be-hind this relationship.