Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

ObjectiveThis study explores the methods of lung tissue extraction and fixation required for pathological studies of fetal rats, based on the unique physiological structure of fetal rat lung tissue and existing lung tissue fixation techniques for adult rats. MethodsSix pregnant adult SD rats at 20.5 days of gestation were subjected to cesarean section to obtain fetal rats. Four healthy fetal rats with similar body weight, vital signs, and respiratory status were selected from each pregnant rat, and they were randomly divided into the following groups using a random number table: direct lung infiltration group, lung infiltration group after intratracheal infusion, whole-body infiltration group of fetal rats, and whole-body infiltration group after intratracheal infusion of fetal rats. To systematically compare and analyze the anatomical morphology under different fixation methods, lung tissues from four groups of fetal rats were harvested, perfused, and fixed, and the gross morphology of lung tissues in each group was observed. Paraffin sections were prepared and stained with Hematoxylin-Eosin (H&E). The histological morphology of the whole lung, alveoli, and bronchi was further examined under optical microscopy. ResultsIn the direct lung infiltration group, the hilar structures were unclear, lung lobation was indistinct, the shape was irregular, lung cavities were small, and alveoli and bronchi were shrunken. In the lung infiltration group after intratracheal infusion, the hilar structures were clear, lobation was pronounced, the shape was regular, lung cavities were large, and alveoli and bronchi were full. Both the whole-body infiltration group and whole-body infiltration group after intratracheal infusion of fetal rats exhibited visible lungs, hearts, skins, and other organs. The lung tissues of both groups showed obvious lobulation, irregular shape, and damage at the margins of lung lobes. In the whole-body infiltration group, the thoracic cavities of the fetus were flattened, lung cavities were small, and alveoli and bronchi were shrunken. In the whole-body infiltration group after intratracheal infusion of fetal rats, the fetal thoracic cavities were full, lung cavities were large, and alveoli and bronchi were relatively full. ConclusionThe lung infiltration after intratracheal infusion method for fetal rat lung tissue fixation outperforms direct lung infiltration, whole-body infiltration of fetal rats, and whole-body infiltration after intratracheal infusion of fetal rats in terms of preservation of the lung tissue's original morphology, paraffin sectioning, staining, and pathological observation and analysis. The embedding, sectioning, and staining processes are also simple and save consumables. Therefore, intratracheal infusion followed by lung infiltration method is recommended for fixation in histopathological observation of fetal rat lung tissue.

Kirsten rat sarcoma viral oncogene homolog (KRAS) protein inhibitors are a promising class of therapeutics, but research on molecules that effectively penetrate the blood-brain barrier (BBB) remains limited, which is crucial for treating central nervous system (CNS) malignancies. Although molecular generation models have recently advanced drug discovery, they often overlook the complexity of biological and chemical factors, leaving room for improvement. In this study, we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug efficacy and drug absorption properties. Our approach utilizes a variational autoencoder (VAE) generative model integrated with reinforcement learning for multi-objective optimization. This method specifically aims to enhance BBB permeability (BBBp) while maintaining high-affinity substructures of KRAS inhibitors. To support this, we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models. Additionally, we introduce two novel metrics, the knowledge-integrated reproduction score (KIRS) and the composite diversity score (CDS), to assess structural performance and biological relevance. Retrospective validation with KRAS inhibitors, AMG510 and MRTX849, demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications. This study provides a robust framework for accelerating the structural enhancement of lead compounds, advancing the drug development process across diverse targets.

Objective To observe the expression of adhesion molecule CD226 on the small intestinal group 3 innate lymphoid cells (ILC3) in mice. Methods The bioinformatics was used to analyze the expression of CD226 on murine ILCs. Small intestinal mucosal lamina propria lymphocytes (LPL) were isolated from wild-type C57BL/6J mice, and the expression of CD226 on ILC1 and ILC3 was detected by flow cytometry. A mouse model of dextran sulfate sodium (DSS)-induced colitis was constructed to observe the changes in the expression of CD226 on ILC3. Results Both ILC1 and ILC3 in the mice small intestine expressed CD226 molecules; the proportion of ILC3 was reduced, while the expression level of CD226 on ILC3 was increased in the colitis model. Conclusion CD226 is expressed on the small intestines of mice, and although the proportion of ILC3 decreases in the DSS-induced colitis, the expression of CD226 on ILC3 increases.
Animals ; Mice ; Colitis/chemically induced* ; Immunity, Innate ; Intestine, Small ; Lymphocytes ; Mice, Inbred C57BL

Objective To investigate the effect of Yu's Qingre Huoxue prescription enema on colonic mucosa in rats with ulcerative colitis(UC).Methods A total of 30 Wistar rats were randomly divided into blank control group,model group,mesalazine group,Chinese medicine high-dose,medium-dose and low-dose groups(5 rats in each group).After successful modeling with trinitrobenzene sulfonic acid,the rats were given 14 days enema with distilled water,mesalazine suspension,and high,medium and low concentration Yu's Qingre Huoxue prescription.The general condition and weight changes of rats were recorded daily,and colon macroscopic damage index(CMDI)and mucosal injury score under microscope of rats in each group were compared.Results Compared with blank control group,the weight of rats in model group decreased significantly(P<0.05).The blank control group had normal water and food intake and activity,glossy fur and normal stool.The rats in model group and each administration group were found to have anal fouling,residual blood in stool,decreased appetite,messy fur,dim luster and other conditions,and the above conditions were gradually improved after enema treatment.Compared with blank control group,the CMDI and mucosal injury scores of model group were significantly increased(P<0.05).Compared with model group,CMDI and mucosal injury scores of mesalazine group and Chinese medicine high-dose,medium-dose and low-dose groups were significantly decreased(P<0.05).Conclusion Yu's Qingre Huoxue prescription can effectively improve the clinical symptoms of diarrhea,mucous,pus and blood stools in UC model rats,reduce the damage of colonic mucosa,promote mucosal repair,and have a good effect on the treatment of UC in rats.

Objective To investigate the risk factors of microcirculation obstruction(MVO)after reperfusion in patients with acute myocardial infarction(AMI).Methods Forty-one patients with AMI who received treatment with myocardial reperfusion were retrospectively selected.Cardiac magnetic resonance(CMR)was used to determine whether the patients had MVO.The patients were divided into MVO and non-MVO groups.The basic data,laboratory examination and CMR parameters of patients were collected and compared between the groups,and the risk factors related to MVO were screened out by logistic regression analysis.Results Delayed myocardial enhancement was observed in all 41 patients,among which 11 cases(26.8%)were with MVO.A total of 206 delayed myocardial enhancement segments were observed,of which 77 segments combined with MVO and 129 segments without MVO.AMI patients with MVO had a higher rate of transmural myocardial infarction,greater infarct volume,left ventricular myocardial mass(LVMM)and edema degree,as well as lower ejection fraction of left and right ventricles(P<0.05).Multivariate logistic regression analysis indicated that infarct volume[odds ratio(OR)=1.116,95%confidence interval(CI)1.017-1.224,P=0.020]was an independent risk factor for MVO after AMI reperfusion.Conclusion Infarct volume is an independent risk factor for MVO after AMI reperfusion,and MVO is associated with left and right ventricular function impairment.

Objective:To investigate the diagnostic value of an intelligent assisted grading algorithm for nuclear cataract using anterior segment optical coherence tomography (AS-OCT) images.Methods:A diagnostic test study was conducted.AS-OCT image data were collected from 939 cases of 1 608 eyes of nuclear cataract patients at the Shanghai Tenth People's Hospital of Tongji University from November 2020 to September 2021.The data were obtained from the electronic case system and met the requirements for clinical reading clarity.Among them, there were 398 cases of 664 male eyes and 541 cases of 944 female eyes.The ages of the patients ranged from 18 to 94 years, with a mean age of (65.7±18.6) years.The AS-OCT images were labelled manually from one to six levels according to the Lens Opacities Classification System Ⅲ (LOCS Ⅲ grading system) by three experienced clinicians.This study proposed a global-local cataract grading algorithm based on multi-level ranking, which contains five basic binary classification global local network (GL-Net).Each GL-Net aggregates multi-scale information, including the cataract nucleus region and original image, for nuclear cataract grading.Based on ablation test and model comparison test, the model's performance was evaluated using accuracy, precision, sensitivity, F1 and Kappa, and all results were cross-validated by five-fold.This study adhered to the Declaration of Helsinjki and was approrved by Shanghai Tenth People's Hospital of Tongji University (No.21K216).Results:The model achieved the results with an accuracy of 87.81%, precision of 88.88%, sensitivity of 88.33%, F1 of 88.51%, and Kappa of 85.22% on the cataract dataset.The ablation experiments demonstrated that ResNet18 combining local and global features for multi-level ranking classification improved the accuracy, recall, specificity, F1, and Kappa metrics.Compared with ResNet34, VGG16, Ranking-CNN, MRF-Net models, the performance index of this model were improved.Conclusions:The deep learning-based AS-OCT nuclear cataract image multi-level ranking classification algorithm demonstrates high accuracy in grading cataracts.This algorithm may help ophthalmologists in improving the diagnostic accuracy and efficiency of nuclear cataract.

Objective:To observe the effects of acupuncture and moxibustion at Feishu(BL13)on inflammatory responses and intestinal short-chain fatty acids(SCFAs)in rats with asthma. Methods:Fifty-six Sprague-Dawley rats were randomly divided into a normal group(16 rats)and a modeling group(40 rats).Rats in the modeling group were subjected to establishing asthma models using ovalbumin(OVA).Model evaluation was conducted using 4 rats from each group.The remaining rats that successfully developed asthma were then randomly divided into a model group,an acupuncture group,and a moxibustion group,with 12 rats in each group.Rats in the acupuncture group received acupuncture treatments,and those in the moxibustion group received moxibustion treatments,both at Feishu(BL13)for 30 min.Following the treatments,the rats were exposed to atomization excitation with a 1%OVA solution for 20 min daily for 14 consecutive days.At the end of the experiment,inflammatory markers in the rats'peripheral blood were analyzed using a biochemical method.In addition,inflammatory cells in the bronchoalveolar lavage fluid(BALF)were counted using Wright-Giemsa staining.The lung tissue of rats was examined under a light microscope after staining with hematoxylin-eosin to observe morphological or pathological changes.Furthermore,real-time fluorescence quantitative polymerase chain reaction was utilized to measure the mRNA expression of inflammatory factors in the lung tissue.Lastly,the concentration of SCFAs in the rat's feces was determined using gas chromatography-hydrogen flame ionization. Results:The levels of eosinophils(Eos),neutrophils(Neu),and lymphocytes(Lym)in the peripheral blood,as well as Eos and Neu in the BALF,and the expression of interleukin(IL)-4,IL-5,IL-13,IL-33,and thymic stromal lymphopoietin(TSLP)mRNAs in the lung tissue were all found to be significantly increased(P<0.05 or P<0.01);the lung tissue structure displayed severe injuries;the levels of acetic acid,propionic acid,isobutyric acid,butyric acid,and valeric acid in the feces decreased significantly in the model group(P<0.05 or P<0.01).Compared with the model group,the peripheral blood levels of Eos,Neu,and Lym,as well as Eos in the BALF,and the mRNA expression levels of IL-4 and IL-5 in the lung tissue decreased significantly in both the acupuncture group and the moxibustion group(P<0.05 or P<0.01).This reduction was accompanied by alleviated pathological damage in the lung tissue.Additionally,there were significant increases in the levels of acetic acid,propionic acid,isobutyric acid,and butyric acid in the feces in both the acupuncture group and the moxibustion group(P<0.05 or P<0.01).In the acupuncture group,the expression levels of Lym in the BALF and IL-13 mRNA in the lung tissue decreased significantly(P<0.05 or P<0.01).In the moxibustion group,the mRNA expression levels of IL-33 and TSLP in the lung tissue also reduced significantly(P<0.05 or P<0.01).Furthermore,the level of valeric acid in the feces increased notably in the moxibustion group(P<0.01).Compared with the acupuncture group,it was found that the mRNA levels of IL-5 and IL-13 in the lung tissue,as well as the acetic acid level in the feces,were significantly higher in the moxibustion group(P<0.05 or P<0.01). Conclusion:Both acupuncture and moxibustion were effective in reducing abnormal inflammation and regulating intestinal SCFAs in asthma model rats.Acupuncture demonstrated superiority in inhibiting pro-inflammatory factors,particularly IL-5 and IL-13,while moxibustion exhibited better regulation on intestinal metabolites SCFAs,especially acetic acid.