Radiomics enables the extraction of high-throughput quantitative features from ophthalmic images, allowing the identification of subvisual information that is imperceptible to the human eye and offering a novel strategy for the precise diagnosis and treatment of retinal diseases. By quantitatively characterizing subtle differences in retinal structure, texture, and hemodynamic characteristics, and integrating these features with clinical data, radiomics has demonstrated substantial potential in early screening, disease stratification, prediction of treatment responses, and individualized risk assessment of retinal diseases, particularly in common conditions such as diabetic retinopathy and age-related macular degeneration. Despite these promising advances, the clinical translation of radiomics remains challenging. Current limitations include suboptimal model performance and generalizability,as well as insufficient clinical interpretability of radiomic feature and predictive models, which hampers their integration into existing imaging systems and routine clinical workflows. Based on a systematic analysis of relevant articles published over the past five years, this paper summarizes recent progress in the application of radiomics combined with machine learning for the diagnosis and prognostic assessment of retinal diseases, and to discuss the key challenges and future directions for its clinical implementation.

Background Liver cancer is one of the common malignant tumors. Phthalates (PAEs), as a widely used class of plasticizers, can participate in the occurrence and progression of liver diseases through multiple pathways. Objective To explore the association between PAEs exposure and liver cancer risk and to provide a scientific basis for the prevention of environment-related tumor risk events. Methods Chi-square test and logistic regression were employed to analyze data from the National Health and Nutrition Examination Survey (NHANES) database between 2001 and 2018, to investigate the association between PAEs exposure and liver cancer. Network toxicology combined with machine learning was used to screen independent prognostic genes associated with PAEs and liver cancer, and to evaluate their correlations with tumor immunity, tumor pathway activation, and tumor drug resistance. Finally, the prediction results were validated using GEO datasets, molecular docking, and molecular dynamics simulations. Results After screening, 11378 eligible samples were obtained from the NHANES database, including 108 patients with liver cancer and 11270 healthy controls. The logistic regression analysis revealed that exposure to nine types of PAEs was positively correlated with liver cancer (OR > 1, P < 0.05). The network toxicology analysis indicated that the association between PAEs exposure and liver cancer was related to three independent prognostic genes: uridine-cytidine kinase 2 (UCK2), glucose-6-phosphate dehydrogenase (G6PD), and albumin (ALB). These three independent prognostic genes were significantly associated with the tumor immune microenvironment, tumor pathway activation, and tumor drug resistance, and exhibited complex interactions with each other. All three independent prognostic genes showed significant differential expression in the validation datasets GSE58043 and GSE115469 (P < 0.05). The results of both molecular docking and molecular dynamics simulations confirmed that these three independent prognostic genes can freely bind to PAEs and form stable complexes. Conclusion Exposure to PAEs is positively correlated with liver cancer. The intrinsic association between the two may involve metabolic disorders, immunosuppression, and activation of inflammatory and tumor-related pathways.

Objective To investigate the factors affecting the exposure of polymyxin B and the correlation between pharmacokinetic/pharmacodynamic(PK/PD)indexes and efficacy in patients with multidrug-resistant Gram-negative bacterial(MDR-GNB)infections.Methods This prospective study was conducted in patients who received polymyxin B to treat MDR-GNB infections in the intensive care unit of Nanjing Drum Tower Hospital,Medical College,Nanjing University from January 2021 to December 2023.Plasma concentrations of polymyxin B were analyzed using a high-performance liquid chromatography-tandem mass spectrometry,and the influencing factors of exposure were investigated.The predictive value of area under the concentration-time curve(AUC24h)and AUC24hto minimum inhibitory concentration ratio for efficacy was determined by the receiver operating characteristic curve.Results The median of AUC24h was 76.11(56.06,96.94)μg·mL-1·h in 96 patients with MDR-GNB infections.Patients in the high-dose group(≥ 150 mg·d-1)were more likely to have higher exposure of polymyxin B than those in the low-dose group(＜150 mg·d-1)(P＜0.05).The exposure in patients with renal replacement therapy was significantly de-creased(P＜0.01).However,increasing the dose in patients receiving renal replacement therapy had no significant difference on exposure.The ROC curve showed AUC24h/MIC was closely correlated with clinical efficacy in patients with MDR-GNB infections(AUCROC=0.724,P＜0.01)and the optimal cut-off value of AUC24h/MIC was 62.1.Subgroup analysis showed that the optimal cut-off values of AUC24h/MIC in patients with and without pulmonary infection were 70.8 and 61.5,respectively.The clinical effi-cacy rate was significantly higher in AUC24 h/MIC≥62.1 group,compared with those in AUC24 h/MIC＜62.1 group(72.88％vs.32.43％,P＜0.01).After treatment,the decreasing trend of inflammation indicators in AUC24 h/MIC≥ 62.1 group was superior to those in AUC24h/MIC＜62.1 group.Conclusion The dose and renal replacement therapy are the significant factors influencing the exposure of polymyxin B.AUC24 h/MIC with the target of 62.1 was the optimal exposure index to predict the efficacy in the treatment of MDR-GNB infections and the optimal threshold of AUC24h/MIC was higher in patients with pulmonary infections than in non-pulmonary patients,so therapeutic drug monitoring is recommended to adjust the AUC24h/MIC index to achieve individual-ized medication.

Teicoplanin,currently one of the preferred drugs for treating infections caused by multidrug-resistant Staphylococcus aureus and Enterococcus in clinical practice,has a high plasma protein binding rate.Most of the drug binds to protein after entering the body,only a portion of the drug exists in a free form.Since the free drug can pass through biological membranes and enter the target tissue to exert its therapeutic effect,monitoring the free teicoplanin blood concentration is clinically important and plays a role in guiding individualized drug therapy.This article summarizes and compares the current methods for determining the concentration of free teicoplanin in the blood,and analyzes their advantages and disadvantages.Based on this,it analyzes the possible factors affecting the concentration of free teicoplanin in the blood,providing a reference for the development of new methods for detecting free teicoplanin concentration and providing more accurate individualized medication plans based on free concentration.

Objective To evaluate the dosimetric impact of interfractional bladder fullness variation in volumetric modulated arc therapy for cervical cancer using artificial intelligence-assisted cone-beam CT(CBCT)image segmentation,and propose an imaging-based quantitative assessment criterion for bladder fullness,providing an objective basis for assessing bladder filling status during clinical treatment.Methods Fifty patients receiving volumetric modulated arc therapy for cervical cancer were selected.The criterion for determining bladder fullness was as follow:if the bladder longitudinal diameter measured on the CBCT mid-sagittal plane was greater than half of the bladder longitudinal diameter measured on the localizable CT,it was defined as≥50%bladder fullness;otherwise,it was defined as<50%bladder fullness.Based on this criterion,two CBCT images were selected for each patient(representing fractions with≥50%and<50%fullness,respectively).Borui auto-contouring system was applied to re-contour the target areas and organs at risk,followed by dose recalculation.Results Compared with≥50%bladder fullness group,<50%bladder fullness group had significantly increased bladder V40,and small bowel Dmax,Dmean,V55,V45,V40(P<0.05),indicating that during interfractional radiotherapy,a CBCT-measured bladder longitudinal diameter less than half of the bladder longitudinal diameter measured on the localizable CT could serve as a predictor for significantly increased radiation dose to the bladder and small bowel.Correlation analysis revealed that bladder volume change showed a positive correlation with bladder Dmax change(R=0.45),a significant negative correlation with bladder V30(R=-0.37),and negative correlations with small bowel Dmax,Dmean,V55,V45,V40(R=-0.31,-0.41,-0.39,-0.49,-0.61).The correlation results indicate that increasing bladder fullness could reduce the radiation dose to the bladder and small bowel.Conclusion Artificial intelligence-assisted segmentation confirms that in interfractional radiotherapy for cervical cancer,when the CBCT-measured bladder longitudinal diameter is less than half of the longitudinal diameter measured on the localizable CT,there is a significant increase in radiation dose to OAR.Maintaining an ideal state of bladder fullness contributes to reducing the radiation dose to the bladder and small bowel.It is crucial to provide patients with adequate bladder management education before treatment and implement strict bladder volume management strategies during treatment fractions.

Objective To investigate the factors affecting the exposure of polymyxin B and the correlation between pharmacokinetic/pharmacodynamic(PK/PD)indexes and efficacy in patients with multidrug-resistant Gram-negative bacterial(MDR-GNB)infections.Methods This prospective study was conducted in patients who received polymyxin B to treat MDR-GNB infections in the intensive care unit of Nanjing Drum Tower Hospital,Medical College,Nanjing University from January 2021 to December 2023.Plasma concentrations of polymyxin B were analyzed using a high-performance liquid chromatography-tandem mass spectrometry,and the influencing factors of exposure were investigated.The predictive value of area under the concentration-time curve(AUC24h)and AUC24hto minimum inhibitory concentration ratio for efficacy was determined by the receiver operating characteristic curve.Results The median of AUC24h was 76.11(56.06,96.94)μg·mL-1·h in 96 patients with MDR-GNB infections.Patients in the high-dose group(≥ 150 mg·d-1)were more likely to have higher exposure of polymyxin B than those in the low-dose group(＜150 mg·d-1)(P＜0.05).The exposure in patients with renal replacement therapy was significantly de-creased(P＜0.01).However,increasing the dose in patients receiving renal replacement therapy had no significant difference on exposure.The ROC curve showed AUC24h/MIC was closely correlated with clinical efficacy in patients with MDR-GNB infections(AUCROC=0.724,P＜0.01)and the optimal cut-off value of AUC24h/MIC was 62.1.Subgroup analysis showed that the optimal cut-off values of AUC24h/MIC in patients with and without pulmonary infection were 70.8 and 61.5,respectively.The clinical effi-cacy rate was significantly higher in AUC24 h/MIC≥62.1 group,compared with those in AUC24 h/MIC＜62.1 group(72.88％vs.32.43％,P＜0.01).After treatment,the decreasing trend of inflammation indicators in AUC24 h/MIC≥ 62.1 group was superior to those in AUC24h/MIC＜62.1 group.Conclusion The dose and renal replacement therapy are the significant factors influencing the exposure of polymyxin B.AUC24 h/MIC with the target of 62.1 was the optimal exposure index to predict the efficacy in the treatment of MDR-GNB infections and the optimal threshold of AUC24h/MIC was higher in patients with pulmonary infections than in non-pulmonary patients,so therapeutic drug monitoring is recommended to adjust the AUC24h/MIC index to achieve individual-ized medication.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

ObjectiveTo study the effect of Taikong Yangxin Pills on the metabolism of simulated weightless rats based on metabolomics and discuss the metabolism mechanism. MethodsIn the simulated space capsule environment on the ground， the rat model of simulated weightlessness was established by the tail suspension method. Rats were randomly grouped as follows： out-of-capsule control， in-capsule control， model， and high （3.0 g·kg^-1） and low （1.5 g·kg^-1） doses of Taikong Yangxin Pills， and they were administrated with corresponding drugs by gavage for 28 days. The serum levels of endogenous metabolites in rats were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF/MS）. The obtained data were processed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） to screen for differential metabolites and potential biomarkers. MetaboAnalyst 5.0 was used for pathway enrichment analysis to explain the metabolic regulation mechanism of the drug. ResultsCompared with the out-of-capsule control group， the in-capsule control group showed elevated levels of thirteen metabolites， including 14-hydroxyhexadecanoic acid， linoleic acid， and α-linolenic acid （P<0.05）， which suggested that the space capsule environment mainly affected the metabolism of α-linolenic acid and linoleic acid in the rats. Compared with the in-capsule control group， the model group showed lowered levels of fourteen metabolites， including 4-imidazolone-5-propionic acid， isocitric acid/citric acid， and L-tyrosine （P<0.05）， which were recovered after the treatment with Taikong Yangxin pills （P<0.05）. The pathway enrichment analysis revealed that weightlessness induced by tail suspension and drug intervention mainly involved the phenylalanine， tyrosine， and tryptophan biosynthesis， tyrosine metabolism， histidine metabolism， and citric acid cycle. ConclusionThe simulated space capsule environment and simulated weightlessness induced by tail suspension can both affect the metabolism level of rats. Taikong Yangxin pills can ameliorate the metabolic abnormality in the rat model of weightlessness by regulating various amino acids and energy metabolism-related pathways.

Objective To evaluate the dosimetric impact of interfractional bladder fullness variation in volumetric modulated arc therapy for cervical cancer using artificial intelligence-assisted cone-beam CT(CBCT)image segmentation,and propose an imaging-based quantitative assessment criterion for bladder fullness,providing an objective basis for assessing bladder filling status during clinical treatment.Methods Fifty patients receiving volumetric modulated arc therapy for cervical cancer were selected.The criterion for determining bladder fullness was as follow:if the bladder longitudinal diameter measured on the CBCT mid-sagittal plane was greater than half of the bladder longitudinal diameter measured on the localizable CT,it was defined as≥50%bladder fullness;otherwise,it was defined as<50%bladder fullness.Based on this criterion,two CBCT images were selected for each patient(representing fractions with≥50%and<50%fullness,respectively).Borui auto-contouring system was applied to re-contour the target areas and organs at risk,followed by dose recalculation.Results Compared with≥50%bladder fullness group,<50%bladder fullness group had significantly increased bladder V40,and small bowel Dmax,Dmean,V55,V45,V40(P<0.05),indicating that during interfractional radiotherapy,a CBCT-measured bladder longitudinal diameter less than half of the bladder longitudinal diameter measured on the localizable CT could serve as a predictor for significantly increased radiation dose to the bladder and small bowel.Correlation analysis revealed that bladder volume change showed a positive correlation with bladder Dmax change(R=0.45),a significant negative correlation with bladder V30(R=-0.37),and negative correlations with small bowel Dmax,Dmean,V55,V45,V40(R=-0.31,-0.41,-0.39,-0.49,-0.61).The correlation results indicate that increasing bladder fullness could reduce the radiation dose to the bladder and small bowel.Conclusion Artificial intelligence-assisted segmentation confirms that in interfractional radiotherapy for cervical cancer,when the CBCT-measured bladder longitudinal diameter is less than half of the longitudinal diameter measured on the localizable CT,there is a significant increase in radiation dose to OAR.Maintaining an ideal state of bladder fullness contributes to reducing the radiation dose to the bladder and small bowel.It is crucial to provide patients with adequate bladder management education before treatment and implement strict bladder volume management strategies during treatment fractions.

The study aims to investigate the effects of adding different proportions of Codonopsis radix compound crude extracts to the rabbit diet on growth performance,immune status,intesti-nal enzyme activity,structure,and microbial composition.A total of 96 5-week-old New Zealand White rabbits were randomly divided into 4 groups,with 6 replicates per group.The control group(BC)was fed a basal diet,while the experimental groups(CM-H and CM-L)were fed a basal diet supplemented with 1 000 mg/kg and 500 mg/kg of Codonopsis radix compound crude extracts,re-spectively.The antibiotic group(CK)was fed a basal diet supplemented with 300 mg/kg of keto-tifen.The experimental period was 42 days.Blood samples were collected at days 21 and 42,and se-rum biochemical and immune markers were determined.Intestinal segments and contents were col-lected at day 42 for analysis of intestinal health.The results showed that compared with the BC group,the average daily gain,feed-to-gain ratio,and diarrhea rate were significantly higher(P＜0.05)in the CM-H and CM-L groups.The total cholesterol(Tchol)content in the serum was sig-nificantly lower in the CM-H group at day 21 and the CM-L group at day 42(P＜0.05).The high-density lipoprotein(HDL)was significantly higher in the CM-H and CM-L groups than in the CK group at day 42(P＜0.05),and the total protein(TP)in the serum was significantly higher in the CM-H and CM-L groups than in the BC group(P＜0.05).The IgG and IgM levels in the serum were significantly higher in the CM-H and CM-L groups than in the BC group(P＜0.05).In the CM-H and CM-L groups,the content of acetic acid in the colon was significantly higher than that in the BC group(P＜0.05).The content of propionic acid in the colon of the CM-L group was also significantly higher than that in the BC group(P＜0.05).The content of α-amylase in the duode-num,the content of trypsin in the duodenum,the pancreas,and the ileum of the CM-H group were significantly higher than those in the BC group(P＜0.05),and the content of trypsin in the duode-num of the CM-H group was significantly higher than those in the BC group and the CM-L group(P＜0.05).Compared with the BC group,the content of GPX1 in the ileum and jejunum of the CM-L group and the ileum of the CM-H group was significantly increased(P＜0.05),and the length of the villi in the duodenum of the CM-H group was significantly increased(P＜0.05).Compared with the BC group,the expression level of ZO-1 in the ileum of the CM-H group was significantly upregulated(P＜0.05),and the expression level of Claudin in the jejunum of the CM-H group and the CM-L group was significantly higher than that in the CK group(P＜0.05).The high-throughput sequencing results showed that the Sob index was significantly higher in the CM-L group compared to the BC group(P＜0.05).At the phylum level,the Firmicutes and Bacteroid-ota phyla were the main phyla.At the genus level,Akkermansia and Ruminococcus were the main genera.The relative abundance of Papillibacter and Eubacterium_ruminantium_group in the CM-L group was significantly higher than that in the CK group(P＜0.05).In summary,adding a Codonopsis radix compound crude extract to the diet can improve the growth performance,immu-nity,antioxidant capacity,integrity of intestinal mucosal structure,enzyme activity in the intestine,and increase the diversity of microorganisms in the blind intestine when the diet is supplemented with 500 mg/kg of Codonopsis radix compound crude extract.