Purpose: Metastatic rectal cancer (mRC) is a highly lethal and complex disease that demands a multidisciplinary treatment approach. However, the clinical effectiveness of radiotherapy (RT) for de novo mRC remains controversial and uncertain. Methods: This retrospective cohort study examined medical records from Kaohsiung Chang Gung Memorial Hospital for patients with histologically confirmed de novo mRC diagnosed between January 2015 and December 2020. All patients received standard systemic therapy and radical surgery when feasible. The primary outcome, overall survival (OS), was assessed using the Kaplan-Meier method. Multivariable analysis was performed using a Cox regression model. Results: Among 271 patients included in the analysis, 117 received RT and 154 did not. The median OS was significantly longer in the RT group compared with the non-RT group (27.8 months vs. 21.9 months; P=0.046). Multivariate analysis identified several independent predictors of OS: age ≥65 years (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.26–2.27; P=0.001), primary tumor resection (HR, 2.62; 95% CI, 1.90–3.61; P<0.001), M1b or M1c disease (HR, 1.97; 95% CI, 1.44–2.69; P<0.001), and receipt of RT (HR, 1.41; 95% CI, 1.02–1.94; P=0.036). Conclusion RT significantly improves OS in patients with mRC, underscoring its role in treatment strategies. These findings support its inclusion in therapeutic protocols and highlight the need for larger, multicenter trials to confirm and extend these results.

“Runner’s high” refers to a momentary sense of pleasure that suddenly appears during running or other exercise activities, characterized by anti-anxiety, pain relief, and other symptoms. The neurobiological mechanism of “runner’s high” is unclear. This review summarizes human and animal models for studying “runner’s high”, analyzes the neurotransmitters and neural circuits involved in runner’s high, and elucidates the evidence and shortcomings of researches related to “runner’s high”. This review also provides prospects for future research. Research has found that exercise lasting more than 30 min and with an intensity exceeding 70% of the maximum heart rate can reach a “runner’s high”. Human experiments on “runner’s high” mostly use treadmill exercise intervention, and evaluate it through questionnaire surveys, measurement of plasma AEA, miRNA and other indicators. Animal experiments often use voluntary wheel running intervention, and evaluate it through behavioral experiments such as conditional place preference, light dark box experiments (anxiety), hot plate experiments (pain sensitivity), and measurement of plasma AEA and other indicators. Dopamine, endogenous opioid peptides, endogenous cannabinoids, brain-derived neurotrophic factor, and other substances increase after exercise, which may be related to the “runner’s high”. However, attention should be paid to the functional differences of these substances in the central and peripheral regions, as well as in different brain regions. Moreover, current studies have not identified the targets of the neurotransmitters or neural factors mentioned above, and further in-depth researches are needed. The mesolimbic dopamine system, prefrontal cortex-nucleus accumbens projection, ventral hippocampus-nucleus accumbens projection, red nucleus-ventral tegmental area projection, cerebellar-ventral tegmental area projection, and brain-gut axis may be involved in the regulation of runner’s high, but there is a lack of direct evidence to prove their involvement. There are still many issues that need to be addressed in the research on the neurobiological mechanisms of “runner’s high”. (1) Most studies on “runner’s high” involve one-time exercise, and the characteristics of changes in “runner’s high” during long-term exercise still need to be explored. (2) The using of scales to evaluate subjects lead to the lacking of objective indicators. However, some potential biomarkers (such as endocannabinoids) have inconsistent characteristics of changes after one-time and long-term exercise. (3) The neurotransmitters involved in the formation of the “runner’s high” all increase in the peripheral and/or central nervous system after exercise. Attention should be paid to whether peripheral substances can enter the blood-brain barrier and the binding effects of neurotransmitters to different receptors are completely different in different brain regions. (4) Most of the current evidence show that some brain regions are activated after exercise. Is there a functional circuit mediating “runner’s high” between these brain regions? (5) Although training at a specific exercise intensity can lead to “runner’s high”, most runners have not experienced “runner’s high”. Can more scientific training methods or technological means be used to make it easier for people to experience the “runner’s high” and thus be more willing to engage in exercise? (6) The “runner’s high” and “addiction” behaviors are extremely similar, and there are evidences that exercise can reverse addictive behaviors. However, why is there still a considerable number of people in the sports population and even athletes who smoke or use addictive drugs instead of pursuing the “pleasure” brought by exercise? Solving the problems above is of great significance for enhancing the desire of exercise, improving the clinical application of neurological and psychiatric diseases through exercise, and enhancing the overall physical fitness of the population.

Objective:To investigate the correlation between peri-coronary fat attenuation index (FAI) and plaque formation in patients with myocardial bridge (MB) of the left anterior descending artery (LAD) using coronary computed tomography angiography (CCTA) and to develop an optimal predictive model to explore the potential application of FAI in the primary prevention of MB related atherosclerosis.Methods:In this retrospective study, prediction models associated with perivascular fat inflammation were developed and validated using both logistic regression and machine learning (ML) algorithm. A training dataset was collected from 253 patients who underwent ≥2 coronary computed tomography angiography (CCTA) with ≥3 months intervals from one tertiary hospital from January 2007 to April 2021 and had baseline CCTA showing no plaques in LAD MB. The median follow-up time was 3.2 years. According to the same criteria, a total of 75 LAD MB patients from four other hospitals were included to form an independent external validation dataset, with a median follow-up time of 1.8 years. Receiver operating characteristic (ROC) curve analysis with integrated discrimination improvement (IDI) and category net reclassification index (NRI) were used to compare the performance of the predictive models.Results:62 patients (24.5%) in the training dataset had proximal plaque formation in LAD MB, while 22 patients (29.3%) in the external validation dataset had plaque formation during the follow-up period. Baseline FAI within the longitudinal distance equal to 30 mm proximal to the MB entrance was an independent predictor ( OR=1.068, P=0.046). According to the model results, ROC curves were plotted. The AUC of Model 1 was 0.822, and the AUCs of Model 2 and 1 were 0.821 and 0.591 in the training dataset. After the DeLong test, the AUC of Model 1 was superior to that of Model 2 ( Z=2.839, P=0.005) and Model 1 ( Z=6.124, P<0.001). These findings were further validated in the external validation dataset, where ML-model 3 yielded the best predictive performance, outperforming the logistic regression-based Model 2 (categorical NRI=0.359, P=0.048; IDI=0.108, P=0.046). Conclusion:FAI measured within the 30 mm proximal to the entrance of MBs due to its prone to plaque development is an independent predictor for atherosclerotic plaque formation. The ML-prediction model based on a decision tree algorithm combines FAI, MB anatomical features, and patient risk factors, which is beneficial for patients undergoing routine CCTA examination to identify inflamed coronary arteries in advance and guide the clinical adoption of more targeted preventive treatment, including anti-inflammatory treatment.

Objective:To analyze the epidemiological characteristics of cases involving monkey injuries at medical institutions surrounding Qianlingshan Park in Guiyang City, and to provide a reference basis for preventive measures to reduce monkey injuries and standardized post-exposure treatment.Methods:A retrospective cross-sectional study was conducted, collecting 1 900 cases of monkey-induced injuries in Qianlingshan Park treated at the outpatient clinic of Guizhou Provincial Center for Disease Control and Prevention and the Department of Surgery at Qianling Hospital, Guiyang City, from 2021 to 2024. Statistical analysis was performed using Pearson′s chi-square test.Results:Total of 1 900 cases of monkey-related injuries in Qianlingshan Park were collected from 2021 to 2024. The exposure time distribution exhibited significant seasonality, with 48.58% of cases occurring during July and August, totaling 923 cases, indicating a peak in the summer. There were 774 male patients and 1 126 female patients, with a ratio of 1∶1.45.and significant differences were observed between different age groups and genders (χ2=195.00, P<0.001), with the highest number of cases occurring in the 0-9 and 20-29 age groups, accounting for 22.05%(419 cases) and 21.79%(414 cases), respectively. The upper limbs were the most common injury site, accounting for 50.84% of the total cases(966 cases in total), with significant differences between gender and injury location (χ2=22.00, P<0.001), Among females, the proportion of injuries to the upper and lower limbs (30.11% and 16.47%, respectively) was higher than that among males (20.74% and 8.63%, respectively). The majority of injuries were classified as Grade Ⅲ, making up 57.38% of cases(1 069 cases in total). Self-treatment after exposure was the most common approach(60.44%), with significant differences observed between wound severity and treatment method (χ2=6.90, P=0.032), Patients with Grade Ⅱ and Grade Ⅲ wounds were more likely to choose self-management (26.84% and 33.23%, respectively) than outpatient management (15.14% and 24.15%). Approximately 98.05% (1 863 cases) of monkey-injured patients had received rabies vaccinations. Conclusions:This study analyzes monkey-related injuries in Qianlingshan Park from 2021 to 2024, clarifying the temporal distribution of injuries, demographic characteristics, injury sites, and treatment methods. The findings provide references for optimizing human-monkey conflict management and the prevention and control of zoonotic diseases in urban ecological parks.

Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.

Objective Under the operation background of Diagnosis-Intervention Packet(DIP),whether there is interaction between reducing medical cost and average length of stay combined with pre-hospitalization mode,and whether there is difference between different departments and diseases in interaction.Methods Based on real-world data from 71 453 patients admitted to Guizhou Provincial People's Hospital from July to December 2021,a two-way analysis of variance was employed.When the interaction effect was statistically significant,parameter estimation was used to determine the magnitude and direction of the interaction effect,followed by subgroup analyses by department and disease.Results Without adjustment,both total medical costs and average length of stay exhibited a negative interaction effect(P＜0.05).Subgroup analyses revealed that in terms of total medical costs,the effect size for the surgical system was 0.18％,lower than that for the internal medicine system(0.70％);for core diseases,it was 6.62％,lower than that for comprehensive diseases(7.71％).Regarding average length of stay,the effect size for the surgical system was 0.55％,better than that for the internal medicine system(0.22％);for core diseases,it was 8.70％,higher than that for comprehensive diseases(2.90％).Conclusion The combination of DIP payment reform and pre-admission management model demonstrates a synergistic effect,effectively reducing patients' medical costs and length of stay.This effect is influenced by disease complexity and the standardization of diagnostic and treatment processes.

Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.

Aim To investigate the effect of thioredox-in-interacting protein(TXNIP)on non-alcoholic fatty liver disease(NAFLD).Methods Littermate male wild(WT)mice and TXNIP gene whole-body knock-out(KO)mice were randomly divided into two groups:(1)normal diet(ND)group,and(2)The high-fat group,which was fed a high-fat diet(HFD)containing 60％fat for 12 weeks.Serum lipid-related indexes,liver injury indicators and hepatic fat content were detected using commercial kits.The protein lev-els of TXNIP,SLC25A1,SLC13A5,ACLY,CPT1a and PPARα were detected by Western blot.The gene ex-pressions of SLC25A1,SLC13A5 and ACLY were de-tected by RT-PCR.Results High fat diet increased TXNIP protein expression in the liver tissue.Compared with WT-HFD mice,the biochemical indexes in the se-rum and the liver of KO-HFD mice were improved.There was no significant difference in mRNA and pro-tein levels of SLC25A1 between the four groups of mice.For SLC13A5 and ACLY,the mRNA and protein levels of WT-HFD mice were up-regulated compared with WT mice,and these alterations were significantly restored in KO-HFD mice.Besides,compared with WT mice,the protein expressions of the fatty acid oxidation-related protein PPARα and CPT1a proteins in WT-HFD mice decreased,while the protein expressions of PPARα and CPT1 a in KO-HFD mice were significantly enhanced.Conclusion TXNIP gene knockout can improve hepatic steatosis and delay the progression of NAFLD by inhibiting the carbon flux of fatty acid syn-thesis and promoting fatty acid oxidation.

Objective Under the operation background of Diagnosis-Intervention Packet(DIP),whether there is interaction between reducing medical cost and average length of stay combined with pre-hospitalization mode,and whether there is difference between different departments and diseases in interaction.Methods Based on real-world data from 71 453 patients admitted to Guizhou Provincial People's Hospital from July to December 2021,a two-way analysis of variance was employed.When the interaction effect was statistically significant,parameter estimation was used to determine the magnitude and direction of the interaction effect,followed by subgroup analyses by department and disease.Results Without adjustment,both total medical costs and average length of stay exhibited a negative interaction effect(P＜0.05).Subgroup analyses revealed that in terms of total medical costs,the effect size for the surgical system was 0.18％,lower than that for the internal medicine system(0.70％);for core diseases,it was 6.62％,lower than that for comprehensive diseases(7.71％).Regarding average length of stay,the effect size for the surgical system was 0.55％,better than that for the internal medicine system(0.22％);for core diseases,it was 8.70％,higher than that for comprehensive diseases(2.90％).Conclusion The combination of DIP payment reform and pre-admission management model demonstrates a synergistic effect,effectively reducing patients' medical costs and length of stay.This effect is influenced by disease complexity and the standardization of diagnostic and treatment processes.

This study analyzed the clinical characteristics,diagnosis,treatment,and outcomes of disseminated Tsalaromycosis marneffei(DTSM)in non-HIV-infected patients.A retrospective analysis was conducted on 20 cases of non-HIV-infected DTSM treated at Guangzhou Chest Hospital between January 2015 and December 2021.Clinical data,including demographic characteris-tics,time to diagnosis,clinical manifestations,comorbidities,treatment details,and outcomes,were collected and analyzed.Among the 20 cases,9 were in males,and 11 were in females;the median age was 46(range:1-70)years.The median time from symptom onset to definitive diagnosis was 12(range:1-24)months,and 16 cases were initially misdiagnosed with mycobacterial disease.More than half the patients exhibited four major clinical features:fever,lymphadenopathy,skin lesions,and bone lesions.Pulmonary imag-ing abnormalities were observed in 19 cases,and an average of(3.6±1.6)lung lobes were involved.The positive detection rate of multi-sample cultures(70%,14/20)was significantly higher than that identified through histopathological examination(25%,5/20)(χ2=8.120,P=0.004).Findings for all five patients with positive next-generation sequencing(NGS)results were further confirmed through pathogen culture or histopathology.After antifungal treatment,14 patients showed clinical improvement and were discharged.In conclusion,non-HIV-infected DTSM is characterized by complex clinical manifestations and extensive pulmonary involvement,thus leading to frequent misdiagnosis and diagnostic delays.Pathogen detection methods,such as multi-sample cultures and NGS,demonstrate superior diagnostic accuracy to histopathological examination.Early identification and standardized antifungal therapy are critical factors in determining patient outcomes.