AIM:To investigate the effect of apoptosis stimulation protein 2(ASPP2)on the development of traumatic proliferative vitreoretinopathy(PVR)in a rabbit model.METHODS:A total of 30 New Zealand white rabbits were selected, and the right eyes of all rabbits were inflicted with a scleral penetrating wound of approximately 6 mm. Then rabbits were randomly and evenly divided into experimental and control group. The experimental group received an intravitreal injection of 0.1 mL of ARPE-19 cell suspension transfected with lentivirus-ASPP2, while the control group received an intravitreal injection of 0.1 mL of ARPE-19 cell suspension transfected with negative control lentivirus. At 1, 2, 3, and 4 wk after PVR modeling, a handheld tonometer was used to measure the intraocular pressure. Moreover, fundus photography and ocular ultrasound examination were performed to detect the retinal proliferation. At 4 wk after modeling, hematoxylin-eosin staining was used to observe the morphological retinal changes, and Western blot was used to determine the protein expressions of ASPP2 and the epithelial-mesenchymal transition(EMT)marker Vimentin in the rabbit retinas.RESULTS:At 1, 2, 3, and 4 wk after modeling, there were no significant changes in intraocular pressure within the experimental and control group of rabbit eyes, either before or after PVR modeling, the success rate of PVR modeling in the experimental group was lower than that in the control group(P<0.05), and the retinal proliferation and structural disorder was less severe in the experimental group. At 4 wk after modeling, the retinal protein expression level of ASPP2 in the experimental group was significantly higher than that in the control group(t=3.193, P=0.033), while the Vimentin protein expression level was significantly lower in the experimental group(t=-3.599, P=0.023).CONCLUSION:ASPP2 may be involved in regulating the process of EMT in retinal pigment epithelial cells, thereby delaying the development and progression of traumatic PVR in rabbit eyes.

Objective To establish a model that integrates ultrasound features and immunological characteristics for predicting the efficacy of neoadjuvant chemotherapy(NAC)in breast cancer patients.Methods A total of 203 breast cancer patients undergoing preoperative NAC at the Fifth Medical Center of the PLA General Hospital between July 2021 and July 2024 were screened.In line with the inclusion/exclusion criteria,177 patients were included.Data on ultrasound and immunohistochemistry was collected.These patients were divided into pathological complete response(pCR)and non-pathological complete response(non-pCR)groups based on postoperative pathology.Factors with P＜0.0 1 in univariate analysis were evaluated using multivariate Logistic regression.Independent predictive factors were used to construct and validate the ultrasound-immunohistochemical model via Bootstrap.Results The reduction rateof the maximum diameter of lesions,posterior echo attenuation,PR status and HER-2 status were identified as independent predictors of pCR(all P＜0.05).The model proved to be highly accurate and stable.Conclusion The model that combines ultrasound and immunohistochemical features can effectively evaluatep CR after NAC in breast cancer patients.

Objective To analyze the efficacy of arsenic-containing TCM compounds in treating high-risk myelodysplastic syndromes(HR-MDS)with spleen-kidney deficiency and toxic stagnation and blood stasis syndrome;To provide references for the clinical treatment of HR-MDS.Methods The medical records of HR-MDS with spleen-kidney deficiency and toxic stagnation and blood stasis syndrome treated with arsenic-containing TCM compounds in Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2016 to September 2022 were retrospectively analyzed.The patients were divided into arsenic-containing TCM compounds combined with demethylation drugs(HMAs)treatment group and arsenic-containing TCM compounds combined with androgen treatment group.The clinical efficacy of both groups were evaluated,including overall response rate(ORR),median overall survival(OS),1-,2-and 3-year survial rates,median progression free survival(PFS),and 1-,2-and 3-year PFS rates.Results Among 200 cases of HR-MDS,68 cases were treated with arsenic-containing TCM compounds combined with HMAs,and 132 cases were treated with arsenic-containing TCM compounds combined with androgen.The ORR was 30%,and the OS of HR-MDS after treatment was 42 months.The 1-,2-and 3-year survival rates were 78.6%,60.4%and 50.2%respectively.The median PFS was 15 months,and the 1-year,2-year and 3-year PFS rates were 57.8%,28.8%and 18.2%respectively.The ORR of 68 cases HR-MDS treated with arsenic-containing TCM compounds combined with HMAs was 44.1%.After treatment,the median OS of HR-MDS was 42 months,and the survival rates of 1-,2-and 3-years were 84%,75.6%and 61.9%respectively,and the median PFS was 24 months,and the PFS rates of 1-,2-and 3-years were 74.3%,48.5%and 35.2%,respectively.The ORR of 132 cases of HR-MDS treatmented with arsenic-containing TCM compounds combined with androgen was 26.5%,including 33.3%in the high-risk group of HR-MDS and 13.3%in the extremely high-risk group of HR-MDS.There was statistical significance between the two groups(P=0.014).After treatment,the median OS of HR-MDS was 29 months,and the survival rates of 1-,2-and 3 years were 78.6%,54.1%and 45.1%respectively.The median PFS was 13 months,and the PFS rates of 1-,2-and 3 years were 54.1%,28.2%and 12.9%respectively.Conclusion The arsenic-containing TCM compounds combined with HMAs can significantly prolong survival and delay disease progression in HR-MDS.Although the arsenic-based TCM compounds combined with androgen therapy demonstrate inferior efficacy compared to HMAs-based regimens,it has achieved significantly higher OS and PFS than historical controls,serving as an effective alternative for patients intolerant to HMAs.

Objective To investigate the clinical significance of the modified respiratory rate-oxygenation(ROX)index incorporating heart rate(HR)in patients undergoing high flow nasal cannula(HFNC)therapy,and to compare the value of ROX-HR and ROX indices in early prediction of HFNC outcomes.Methods Patients who received continuous HFNC therapy in department of intensive care unit of Tianjin First Central Hospital from January 2022 to June 2023 were selected as study subjects.A total of 153 patients were included in the analysis.Of these,103 patients(67.3%)received HFNC due to acute respiratory failure,while 50 patients(32.7%)started HFNC after extubation.Patients were divided into HFNC success and HFNC failure groups based on the success of HFNC therapy.HR and ROX indices were recorded before HFNC initiation and at 1,2,4,6,8,10,12,18,24,and 48 hours after HFNC initiation,and the ROX-HR index was calculated.Plot the receiver operator characteristic curve(ROC curve),and calculate area under the curve(AUC)to evaluate the predictive value of ROX-HR and ROX index for success and failure of HFNC in patients with acute respiratory failure receiving HFNC treatment after extubation.Results Among patients with acute respiratory failure undergoing HFNC,HFNC failure was associated with higher acute physiology and chronic health evaluationⅡ(APACHEⅡ)and sequential organ failure assessment(SOFA)scores[APACHEⅡscore:19.86(14.26,27.41)vs.16.24(13.60,22.69),SOFA score:5(4,6)vs.4(3,5),both P<0.05].Among patients who started HFNC after extubation,immunocompromised status was a significant factor associated with HFNC failure,with a higher proportion of immunocompromised patients in the HFNC failure group compared to the HFNC success group[77.8%(14/18)vs.31.3%(10/32),P<0.05].For patients with acute respiratory failure starting HFNC,the ROX-HR index could effectively distinguish HFNC success from failure at all time points(AUC>0.650).For patients who started HFNC after extubation,the ROX-HR index remained lower in the HFNC failure group.However,unlike the ROX-HR index,the ROX index seemed unable to effectively differentiate HFNC success from failure,with no significant statistical differences between the HFNC success and failure groups at 2,4,8,18,and 48 hours after extubation.In patients who started HFNC after extubation,HR alone could predict HFNC outcomes,with AUC and 95%confidence intervals(95%CI)of 0.695(0.530-0.860)and 0.698(0.527-0.868)at 2 hours and 4 hours,respectively,and P values of 0.041 and 0.038,respectively.Conclusion The ROX-HR index is a promising tool for early identification of patients at high risk of HFNC failure.

Chrysophanol(Chr)and physcion(Phy)are primary active ingredients of a well-known traditional Chinese medicine namely rhubarb(Chinese name:Dahuang),and their glucuronides have been revealed as the dominant forms presenting in rats after oral administration.Either Chr or Phy has two glycosylation sites,resulting in a pair of positional isomers for glucuronides of either compound(CG1&CG2 and PG1&PG2).To confirmatively identify these glucuronides,energy-resolved mass spectrometry(ER-MS)was used to pursue the fragmentation trajectories of the targeted fragment ions,and the resultant breakdown graphs that were described by the optimal collision energy(OCE)were expected to exhibit the differences of glycosidic bond cleavage between the isomers.Quantum chemical calculation was thereafter conducted to produce the bond dissociation energy(BDE)of the glycosidic bonds.The isomers were unambiguously identified through applying the positive correlation rule between OCE and BDE.Fortunately,the glucuronides of Chr and Phy in vivo were observed through liver microsomes incubationin vitro.ER-MS was utilized to collect the Gaussian-shaped breakdown graphs in response to the neutral loss of 176 Da,and the absolute values of OCE were compared between positional isomers.The results revealed that CG1(-32.31 eV)>CG2(-31.61 eV),and nonetheless,PG1(-30.00 eV)Chr-8-GluA(-48.787 kJ/mol),and nonetheless,Phy-1-GluA(-48.672 kJ/mol)

Objective:To establish ferroptosis-related risk characteristics, to evaluate the prognostic correlation of ferroptosis-related genes in hepatocellular carcinoma, and to explore the complex relationship between hepatocellular carcinoma, ferroptosis and immune microenvironment.Methods:The bioinformatics analysis involved obtaining ferroptosis-related differentially expressed genes (DEGs) from the GeneCards database and the cancer genome atlas database. The biological functions of ferroptosis-related DEGs were analyzed using gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment. Ferroptosis-related DEGs clusters were identified using univariate Cox regression analysis and cluster analysis, etc. The correlation between ferroptosis-related DEGs clusters and tumor immune microenvironment and tumor occurrence score was evaluated using immunopanoramic analysis and tumor-related score analysis. Based on ferroptosis-related characteristics, a ferroptosis-related characteristic spectrum and nomogram were constructed using multivariate Cox regression and correlation analysis, etc. The correlation between the risk characteristics and tumor immune microenvironment, tumor occurrence score and gene mutation were evaluated using immune panoramic analysis, tumor-related score analysis and gene mutation analysis. In the experimental verification stage, the mRNA expression levels of aurora kinase A ( Aurka), acetyl-CoA carboxylase alpha ( Acaca) and arrestin domain containing 3 ( Arrdc3) in mouse primary hepatocytes and mouse hepatoma Hepa1-6 cells were verified by real-time reverse transcription-PCR (RT-qPCR). The mRNA expression levels of AURKA, ACACA and ARRDC3 in adjacent normal tissues and tumor tissues of patients with hepatocellular carcinoma were verified by RT-qPCR. A heat map was used to show the correlation between clustering and clinical parameters, and this was analyzed using a chi-square test. Significance analysis was performed using a two-sided unpaired t test. Results:A total of 35 up-regulated genes and 19 down-regulated genes were identified. These genes were mainly involved in biological processes and signaling pathways related to ferroptosis, oxidative stress and fatty acid metabolism. A total of 14 ferroptosis-related DEGs were identified to be associated with prognosis. The clusterring effect was best when hepatocellular carcinoma patients were divided into two subgroups. The survival rate of cluster 2 was lower than that of cluster 1 ( P<0.05). There was no significant difference in the tumor immune dysfunction and exclusion (TIDE) score between cluster 2 and cluster 1 ( P=0.43). Cluster 1 exhibited higher levels of immune cell infiltration, particularly CD4 + T cells ( P<0.01). The expression levels of 10 major histocompatibility complex (MHC) molecule-related genes were higher in cluster 1. The angiogenesis activity score ( P=0.048) and stemness score ( P=0.038) of cluster 2 were increased, and the expression levels of programmed death-1 ( PDCD1) and cytotoxic T lymphocyte-associated antigen-4 ( CTLA-4) in cluster 2 (5.924±0.013 and 5.475±0.042) were higher than those in cluster 1 (4.539±0.143 and 4.372±0.176) (both P<0.05). The expression levels of AURKA, glucose-6-phosphate dehydrogenease ( G6PD), ACACA, GABA type A receptor associated protein like 1 ( GABARAPL1) and ARRDC3 were correlated with the T stage, clinical stage and survival status of hepatocellular carcinoma. The survival rate of the high-risk group was lower than that of the low-risk group with time ( P<0.01). The area under the curve of the risk characteristics at 1, 3 and 5 years was 0.797, 0.717 and 0.639, respectively. The actual survival time 1, 3, and 5 years was highly consistent with the corresponding predicted survival time. The levels of memory B cell infiltration, angiogenesis activity score and cell stemness score, programmed death-ligand 1, CTLA-4, hepatitis A virus cell receptor 2, lymphocyte activation gene 3 and PDCD1 gene expression (0.013 8±0.036 0, 0.884±0.212, 0.387±0.135, 6.273±0.228, 5.847±0.331, 8.179±0.259, 6.859±0.263 and 5.142±0.326) in the high-risk group were higher than those in the low-risk group (0.001 5±0.021 0, 0.874±0.132, 0.298±0.125, 5.866±0.132, 3.742±0.237, 7.236±0.321, 6.324±0.242 and 4.513±0.211) ( P<0.05, 0.01). The expression levels of MHC molecule-related genes in the high-risk group were also higher than those in the low-risk group ( P<0.05, 0.01), while the infiltration levels of resting mast cells, activated natural killer cells, and resting natural killer cells (0.043 2±0.135 0, 0.032 1±0.143 0 and 0.016 3±0.001 9) and the TIDE score (0.072 0±0.018 0) in the high-risk group were lower than those in the low-risk group (0.054 9±0.023 0, 0.042 7±0.017 0, 0.024 6±0.021 2 and 0.094 0±0.013 5) ( P<0.05, 0.01). The top five genes with the highest mutation frequency in the high-risk group were tumor protein P53 ( TP53, 43%), titin ( TTN, 21%), catenin beta 1 ( CTNNB1, 20%), mucin 16 ( MUC16, 18%) and piccolo presynaptic cytomatrix protein ( PCLO, 11%). The top five genes with the highest mutation frequency in the low-risk group were CTNNB1 (30%), TTN (24%), albumin ( ALB, 16%), MUC16 (15%) and PCLO (11%). The cube protein and PCLO showed the co-occurrence of gene mutations in the high-risk group, while MUC16 and axis 1 protein showed the co-occurrence of gene mutations in the low-risk group. There was no significant difference in tumor mutation burden (TMB) between the high-risk group (1.374±0.026) and the low-risk group (1.303±0.081) ( P=0.073). There was no significant difference in survival time between the high-TMB group (2.3 years) and the low-TMB group (3.8 years) ( P=0.293). The mutation rates of AURKA, G6PD, ACACA, GABARAPL1 and ARRDC3 genes (2.0%, 2.0%, 4.0%, 0.3% and 0.6%) were relatively low. The relative expression levels of Aurka, Acaca and Arrdc3 mRNA in Hepa1-6 cells (13.331±0.000, 6.619±0.000 and 1.209±0.002) were higher than those in mouse primary hepatocytes (1.000±0.000, 1.000±0.000 and 1.000±0.000) (all P<0.01). The relative expression levels of AURKA, ACACA and ARRDC3 mRNA in tumor tissues of patients with hepatocellular carcinoma (2.102±0.365, 2.476±0.351 and 11.460±9.189) were higher than those in adjacent normal tissues of patients with hepatocellular carcinoma (1.122±0.648, 0.831±0.935 and 0.852±0.171) ( P<0.05, 0.01). Conclusions:This study constructed a prognostic signature comprising five ferroptosis-related genes ( AURKA, G6PD, ACACA, GABARAPL1, and ARRDC3) that is highly correlated with clinical hepatocellular carcinoma data. This study highlights the significance of ferroptosis-related genes as prognostic markers for hepatocellular carcinoma and provides insights into the complex relationship between hepatocellular carcinoma, ferroptosis, and the immune microenvironment.

Luxembourg boasts a strategically advantageous geographical location, a robust economic foundation, and an open cultural environment, all of which serve as essential pillars for the promotion of TCM. Its population is diverse and enjoys a significantly high average life expectancy; however, it faces notable health challenges such as chronic diseases, excessive alcohol consumption, obesity, and an aging population. The citizens benefit from extensive medical coverage, access to high-quality healthcare services, and substantial public investment in healthcare. Modern medicine forms the backbone of its healthcare system while traditional therapies, such as acupuncture and moxibustion, play a complementary role as alternative treatments. The development of TCM in Luxembourg has been influenced by neighboring countries, promoted by TCM experts, and supported by the government. At present, TCM is mainly regulated in Luxembourg based on modern medical regulations and relevant EU standards. Its clinical application in health care and chronic disease management has become increasingly important. Relevant education and training are also gradually promoted through international cooperation with the support of the government. It is suggested to promote the establishment of relevant legal norms of local TCM; promote the service and application of TCM to continuously adapt to market demand and sustainable development; increase support to deepen the research and education of TCM, and realize the in-depth promotion and application of TCM in Luxembourg and even in Europe.

Computational approaches,encompassing both physics-based and machine learning(ML)methodolo-gies,have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities.The human dopamine(DA)transporter(hDAT)is the primary therapeutic target of numerous psychi-atric medications.However,traditional hDAT-targeting drugs,which interact with the primary binding site,encounter significant limitations,including addictive potential and stimulant effects.In this study,we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape(WHALES)descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs.Initially,WHALES descriptors facilitated a similarity search,employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates.Consequently,from a compound library of 4,921 marketed and clinically tested drugs,we identified 27 candidate atypical inhibitors.Subsequently,ADMETlab was employed to predict the pharmacokinetic and toxi-cological properties of these candidates,while induced-fit docking(IFD)was performed to estimate their binding affinities.Six compounds were selected for in vitro assessments of neurotransmitter re-uptake inhibitory activities.Among these,three exhibited significant inhibitory potency,with half maximal inhibitory concentration(IC50)values of 0.753 μM,0.542 μM,and 1.210 μM,respectively.Finally,molecular dynamics(MD)simulations and end-point binding free energy analyses were con-ducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation.In conclusion,our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

Objective:To investigate the acute effects of persistent high exposure to atmospheric fine particulate matter (PM 2.5) on residents' outpatient visits for respiratory diseases. Methods:We collected daily outpatient records from 92 hospitals in 13 cities across the Beijing-Tianjin-Hebei region, along with daily PM 2.5, nitrogen dioxide (NO 2), and meteorological data from 2013 to 2018. Five persistent high PM 2.5 exposure scenarios were defined in terms of daily mean PM 2.5 concentrations (>75 μg/m 3 and >150 μg/m 3), duration (≥2 days and ≥3 days), and whether or not there was concurrent exposure to high levels of NO 2 (daily mean NO 2 concentration >50 μg/m 3). A two-stage statistical analysis strategy based on a generalized linear model was applied to conduct a time-series analysis to assess the exposure-response relationship between persistent high PM 2.5 exposure scenarios and residents' outpatient visits for a variety of respiratory diseases, and to estimate excess outpatient visits. Results:During the period, M ( Q1, Q3) PM 2.5 and NO 2 concentrations were 61.2 (42.3, 95.1) μg/m 3 and 40.2 (31.4, 54.4) μg/m 3, respectively, and the daily respiratory disease outpatient visits were 57 (52, 66) cases. When compared with non-permanent high PM 2.5 exposure periods, exposure scenarios with PM 2.5 >75 μg/m 3 and lasting for ≥2 days caused an increased risk of outpatient visits for respiratory diseases by 2.10% (95% CI: 1.44%-2.77%), and resulted in 43 787 (95% CI: 30 025-57 757) excess visits; in this scenario, the concurrent exposure to high levels of NO 2 had a greater acute effect on respiratory disease visits than the absence of exposure to high levels of NO 2 ( P<0.001). The risk of respiratory disease visits increased substantially by 4.41% (95% CI: 3.15%-5.68%) when the daily mean PM 2.5 concentration exceeded 150 μg/m 3 for ≥2 days. Subgroup disease analyses showed that scenarios with daily mean PM 2.5 concentrations exceeding 75 μg/m 3 for ≥3 days caused a significant increase in the risk of lower respiratory tract infections, chronic lower respiratory disease, and asthma visits. Conclusions:Sustained persistent high PM 2.5 exposure increases the risk of outpatient visits for various respiratory diseases; concurrent exposure to high concentrations of NO 2 leads to a greater risk of visiting the clinic, suggesting that the prevention and control of PM 2.5 pollution should be synchronized with the control of mobile source emissions, to synergistically manage the compound pollution of PM 2.5 and NO 2 in the atmosphere.

[Objective]To explore the medication patterns of WU's tumor school for anti-metastasis through"enhancing health and promoting detoxification"based on data mining.[Methods]Systematically review the literature related to the prescription and medication patterns of WU Liangcun in the treatment of tumor metastasis,and summarize his clinical experience in the use of the"enhancing health and promoting detoxification"method.Complete case records of lung cancer,gastric cancer and colorectal cancer metastasis treated by SHEN Minhe,WANG Binbin and RUAN Shanming from January 1,2020 to August 31,2023 were collected.Data mining analysis was performed on the effective prescriptions by using the Traditional Chinese Medicine Inheritance Computer System(V3.5).[Results]A total of 3 023 prescriptions from SHEN Minhe were included,involving 344 types of Chinese herbs.Codonopsis Radix was frequently used,and common herb pairs included Codonopsis Radix,Poria cocos-Atractylodis Macrocephalae Rhizoma.WANG Binbin's 2 654 prescriptions involved 370 types of Chinese herbs.Paeoniae Radix Alba was frequently used,and common pairs included Coicis Semen,Fagopyri Dibotryis Rhizoma-Hedyotis diffusa Willd.RUAN Shanming's 1 182 prescriptions included 257 types of herbs.Astragali Radix was frequently used,and common pairs included Astragali Radix,Alismatis Rhizoma-Scutellariae Radix.WU's tumor school prefers to use herbs with sweet,bitter and acrid flavors,as well as neutral,cold and warm properties,avoiding excessive purgation or tonification and extreme cold or heat.They advocated for gentle tonification and gradual adjustment,as well as a balanced combination of cold and heat.In terms of meridian tropism,they focused on using herbs that entered the spleen and lung meridians,targeting the pathogenesis of spleen and stomach deficiency,which led to the accumulation of dampness and phlegm,emphasized the simultaneous regulation of the spleen and lung,to strengthen the spleen and stomach,eliminate dampness and phlegm,regulate the flow of Qi and clear cancerous toxins.[Conclusion]WU's tumor school has been passed down for three generations,following the principle of"enhancing health and promoting detoxification".The overall medication is balanced and tailored to different types of malignant tumors,demonstrating significant clinical efficacy.