Objective: This study aimed to examine morphological changes and changes in the extracellular signal-regulated kinase (ERK) and cyclic AMP response element-binding protein (CREB) activity in the testes of bulls with cryptorchidism. Methods: Testes from the 18-month-old unilateral cryptorchid bulls, including the descended (normal) and undescended (cryptorchid) testes from each animal, were analyzed through gross examination, histology, immunohistochemistry (Ki-67, phosphorylated p-ERK, p-CREB), and Western blotting. Results: Cryptorchid testes were smaller and exhibited reduced epithelial thickness, although seminiferous tubule area remained unchanged. Expression of Ki-67, p-ERK, and p-CREB was significantly decreased, indicating impaired cell proliferation and signaling.Total ERK and CREB protein levels were unchanged, but phosphorylation levels were notably reduced in cryptorchid samples. Conclusions and Relevance: Our findings demonstrate that cryptorchidism alters testicular morphology and disrupts key signaling pathways, particularly those involved in cell growth and function. Such alterations may contribute to infertility and highlight the importance of early diagnosis and intervention in the context of reproductive management in livestock.

Purpose: Several predictive models have been developed to predict the pathological complete response (pCR) after neoadjuvant chemotherapy (NAC); however, few are broadly applicable owing to radiologic complexity and institution-specific clinical variables, and none have been externally validated. This study aimed to develop and externally validate a machine learning model that predicts pCR after NAC in patients with breast cancer using routinely collected clinical and demographic variables. Methods: The electronic medical records of patients with advanced breast cancer who underwent NAC before surgical resection between January 2017 and December 2020 were reviewed. Patient data from Seoul National University Bundang Hospital were divided into training and internal validation cohorts. Five machine learning techniques, including gradient boosting machine (GBM), support vector machine, random forest, decision tree, and neural network, were used to build predictive models, and the area under the receiver operating characteristic curve (AUC) was compared to select the best model. Finally, the model was validated using an independent cohort from Seoul National University Hospital. Results: A total of 1,003 patients were included in the study: 287, 71, and 645 in the training, internal validation, and external validation cohorts, respectively. Overall, 36.3% of the patients achieved pCR. Among the five machine learning models, the GBM showed the highest AUC for pCR prediction (AUC, 0.903; 95% confidence interval [CI], 0.833–0.972).External validation confirmed an AUC of 0.833 (95% CI, 0.800–0.865). Conclusion Commonly available clinical and demographic variables were used to develop a machine learning model for predicting pCR following NAC. External validation of the model demonstrated good discrimination power, indicating that routinely collected variables were sufficient to build a good prediction model.

OBJECTIVETo investigate the effect of Zilongjin (ZLJ) on human androgen-dependent type of prostate cancer cell line LNCaP.

METHODSMTT assay, flow cytometry and fluorescence microscopy were used to observe the effect of ZLJ in anti-proliferation, cell cycle arresting and apoptosis induction. RT-PCR was used to examine the effect of ZLJ on expressions of prostate marker gene (PSA), androgen receptor (AR), apoptosis related genes (bcl-2 and bax), and Western blot assay was used to detect the effect on protein expression of bcl-2 and bax.

RESULTSZLJ could cause apparent inhibition on proliferation, induce G0/G1 phase arresting and apoptosis in time- and dose-dependent manner on LNCaP cells. The concentration for inhibiting cell growth by 50% (IC50) in 72 hrs was 0.79 mg/ml. ZLJ could down-regulate the expression of PSA, AR, bcl-2 genes and lower bcl-2 protein expression, but showed ineffective on bax protein expression.

CONCLUSIONZLJ displays its anti-tumor effects by way of inhibiting the cell proliferation, arresting the G0/G1 phase, inducing apoptosis, down-regulating PSA, AR, bcl-2 gene expression and lowering bcl-2 protein expressions.

Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Male ; Neoplasms, Hormone-Dependent ; metabolism ; pathology ; Prostate-Specific Antigen ; biosynthesis ; genetics ; Prostatic Neoplasms ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; Receptors, Androgen ; biosynthesis ; genetics