Stem cell division and its critical role in mammary gland development and tumorigenesis: current progress and remaining challenges.

The origin of breast cancer (BC) has traditionally been a focus of medical research. It is widely acknowledged that BC originates from immortal mammary stem cells (MaSCs) and that these stem cells participate in two division modes: symmetric cell division (SCD) and asymmetric cell division (ACD). Although both of these modes are key to the process of breast development and their imbalance is closely associated with the onset of BC, the molecular mechanisms underlying these phenomena deserve in-depth exploration. In this review, we first outline the molecular mechanisms governing ACD/SCD and analyze the role of ACD/SCD in various stages of breast development. We describe that the changes in telomerase activity, the role of polar proteins, and the stimulation of ovarian hormones subsequently lead to two distinct consequences: breast development or carcinogenesis. Finally, gene mutations, abnormalities in polar proteins, modulation of signal-transduction pathways, and alterations in the microenvironment disrupt the balance of breast cancer stem cells (BCSCs) division modes and cause BC. Important regulatory factors such as mammalian Inscuteable (mInsc), Numb, Eya1, PKCα, PKCθ, p53, and IL-6 also play significant roles in regulating pathways of ACD/SCD and may constitute key targets for future research on stem cell division, breast development, and tumor therapy.

Association between anti-Müllerian hormone concentrations and sperm retrieval outcomes in patients with idiopathic nonobstructive azoospermia: a systematic review and meta-analysis.

ABSTRACT: Microdissection testicular sperm extraction (mTESE) is commonly performed to retrieve sperm in the testes for assisted reproductive techniques in patients with idiopathic nonobstructive azoospermia (iNOA). However, the success rate of sperm retrieval varies among individuals. We aim to investigate the association between clinical parameters and sperm retrieval outcomes in patients with iNOA. We searched PubMed, EMBASE, and Web of Science from database inception to August 2, 2023. The main measure was whether sperm retrieval was successful in patients with iNOA who underwent mTESE. Pooled estimates of the sperm retrieval rate and weighted mean differences were calculated using random-effects models. The overall sperm retrieval rate was 36.8% (95% confidence interval [CI]: 27.5%-46.0%, I2 = 95.0%) in nine studies comprising 1892 patients with iNOA. No significant differences were found in age, testicular volume, serum total testosterone concentrations, or inhibin B concentrations between positive and negative sperm retrieval outcomes. Lower anti-Müllerian hormone concentrations in patients with iNOA were associated with a positive outcome of mTESE (weighted mean differences: -2.70; 95% CI: -3.94--1.46, I2 = 79.0%). In conclusion, this study shows a significant relationship between anti-Müllerian hormone and sperm retrieval outcomes in patients with iNOA, while age, testicular volume, total testosterone, and inhibin B show no significant association. These findings have important implications for assessing the potential success of sperm retrieval and selecting appropriate treatment strategies in patients with iNOA.

Testicular volume is a noninvasive predictor of sperm retrieval failure in idiopathic nonobstructive azoospermia.

We investigated the prognostic importance of noninvasive factors in predicting sperm retrieval failure in idiopathic nonobstructive azoospermia (iNOA). We studied 193 patients with nonobstructive azoospermia who underwent microsurgical testicular sperm extraction. The Chi-square test and Mann-Whitney U tests for clinical parameters and seminiferous tubule distribution were used for between-group comparisons. A logistic regression analysis was conducted to identify predictors of retrieval failure. Area under the receiver operating characteristic curve for each variable was evaluated, and the net clinical benefit was calculated using a clinical decision curve. Patients with iNOA had a lower sperm retrieval rate than those with known causes. Moreover, testicular volume was an independent factor affecting sperm extraction outcomes (odds ratio = 0.79, P < 0.05). The testicular volume cut-off value was 6.5 ml (area under the curve: 0.694). The patients with iNOA were categorized into two groups on the basis of the distribution of seminiferous tubules observed. The sperm retrieval rate and testicular volume were significantly different between the groups with a uniform or heterogeneous tubule distribution. There was also a significant association between a uniform tubule distribution and testicular volume. In conclusion, a testicular volume of more than 6.5 ml effectively predicts microsurgical testicular sperm extraction failure due to a uniform tubule distribution in patients with iNOA.

Research advances in imaging markers for predicting hematoma expansion in intracerebral hemorrhage: a narrative review.

Introduction: Stroke is a major global health concern and is ranked as the second leading cause of death worldwide, with the third highest incidence of disability. Intracerebral hemorrhage (ICH) is a devastating form of stroke that is responsible for a significant proportion of stroke-related morbidity and mortality worldwide. Hematoma expansion (HE), which occurs in up to one-third of ICH patients, is a strong predictor of poor prognosis and can be potentially preventable if high-risk patients are identified early. In this review, we provide a comprehensive summary of previous research in this area and highlight the potential use of imaging markers for future research studies. Recent advances: Imaging markers have been developed in recent years to aid in the early detection of HE and guide clinical decision-making. These markers have been found to be effective in predicting HE in ICH patients and include specific manifestations on Computed Tomography (CT) and CT Angiography (CTA), such as the spot sign, leakage sign, spot-tail sign, island sign, satellite sign, iodine sign, blend sign, swirl sign, black hole sign, and hypodensities. The use of imaging markers holds great promise for improving the management and outcomes of ICH patients. Conclusion: The management of ICH presents a significant challenge, and identifying high-risk patients for HE is crucial to improving outcomes. The use of imaging markers for HE prediction can aid in the rapid identification of such patients and may serve as potential targets for anti-HE therapies in the acute phase of ICH. Therefore, further research is needed to establish the reliability and validity of these markers in identifying high-risk patients and guiding appropriate treatment decisions.

Proteomic identification of tumor biomarkers associated with primary gallbladder cancer.

AIM: To identify potential biomarkers of primary gallbladder cancer (PGC). METHODS: Fresh PGC, cholecystitis and normal gallbladder tissue specimens collected from 10 patients, respectively, were subjected to comparative proteomic analysis. The proteomic patterns of PGC were compared with those of cholecystitis and normal gallbladder tissues using two-dimensional gel electrophoresis (2-DE). The differentially expressed proteins were then identified using a MALDI-TOF mass spectrometer (MS) and database searches. To further validate these proteins, 20 samples of PGC tissues and normal tumor-adjacent tissues were collected for Western blot, quantitative real-time PCR, and immunohistochemical staining assay. RESULTS: Seven differentially expressed protein spots were detected by 2-ED analysis by comparing the average maps of PGC, cholecystitis and normal gallbladder tissues. Six of the seven differentially expressed proteins were identified using MALDI-TOF MS, with three overexpressed and three underexpressed in PGC tissue. Protein levels of annexin A4 (ANXA4) were significantly elevated, and heat shock protein 90-beta (Hsp90ß) and dynein cytoplasmic 1 heavy chain 1 (Dync1h1) were decreased in PGC tissues relative to the normal tumor-adjacent tissues as shown by Western blot analysis. However, levels of actin, aortic smooth muscle and gamma-actin were unchanged. In addition, the mRNA levels of all 5 proteins showed similar changes to those of the protein levels (P < 0.01). Further validation by immunohistochemical analysis showed the upregulated expression of ANXA4 and decreased expression of Hsp90ß and Dync1h1 in the cytoplasm of PGC tissues relative to the normal tumor-adjacent tissues. CONCLUSION: Three proteins are identified as potential biomarkers of PGC using proteomic analysis. The functions of these proteins in the carcinogenesis of PGC remain to be studied.

[Frequency distribution and antibiotic resistance of pathogens from the cerebrospinal fluid of 116 children with bacterial meningitis].

OBJECTIVE: To determine the frequency distribution and antibiotic resistance of pathogens isolated from the cerebrospinal fluid samples of children with bacterial meningitis (BM) and to provide a basis for the timely and effective treatment of childhood BM. METHODS: Retrospective analysis was performed on pathogens isolated from 5097 cerebrospinal fluid samples collected from children in Kunming Children's Hospital between January 2008 and June 2012, as well as drug sensitivity test results. Kirby-Bauer antibiotic testing was used to analyze the sensitivity of these pathogens to commonly used antibiotics. RESULTS: A total of 116 pathogen strains were detected from the 5097 cerebrospinal fluid samples, including 77 (66.4%) Gram-positive strains, 30 (25.9%) Gram-negative strains, and 9 (7.8%) fungal strains, with a positive rate of 2.28%. The six most frequently isolated pathogens were Staphylococcus epidermidis (32 strains, 27.6%), Streptococcus pneumoniae (15 strains, 12.9%), Escherichia coli (15 strains, 12.9%), Staphylococcus haemolyticus (9 strains, 7.8%), Cryptococcus neoformans (8 strains, 6.9%) and Staphylococcus aureus (6 strains, 5.2%). Coagulase-negative staphylococci was the predominant pathogen in neonates and young infants with BM, and its sensitivity rates to penicillin, erythromycin and clindamycin were lower than 40%. Streptococcus pneumoniae had a penicillin sensitivity rate of 13.4%, while sensitivity rates to erythromycin and clindamycin reached 60.0%. No Staphylococcus and Streptococcus pneumoniae pathogens resistant to vancomycin were found. Gram-negative bacilli had relatively high sensitivity rates to imipenem, meropenem, cefoperazone/sulbactam and cefepime. CONCLUSIONS: Gram-positive cocci are the predominant pathogens for childhood BM over the past five years. The detected pathogens develop high resistance to commonly used antibiotics. To prevent misdiagnosis, careful attention should be paid to BM caused by Cryptococcus neoformans.