Cyclophosphamide (CP) is a potent chemotherapeutic agent utilized in the treatment of various types of cancer. However, in addition to its efficacy in combating cancer, CP also has severe side effects, including damage to male gonadal functions. This paper aims to explore the cytotoxic properties of CP and its mechanistic impacts on male gonadal functions. The search strategy was conducted using several reviewed articles indexed in PubMed, Science Direct, EBSCO, Scopus, Cochrane Library, Sage Journals, and Google Scholar. CP is an alkylating agent that damages cancer cell DNA, inhibiting growth and division. It also affects healthy cells, leading to severe cytotoxicity. In male gonadal tissues, CP damages germ cells, Leydig cells, and Sertoli cells, causing decreased sperm count, testosterone levels, and disruption of the blood-testis barrier. The metabolism of CP in the liver generates reactive oxygen species, leading to oxidative damage and cell death. Moreover, CP also affects the hypothalamic-pituitary-gonadal axis, regulating male gonadal functions. CP disrupts the production and secretion of gonadotropin-releasing hormone, follicle-stimulating hormone, and luteinizing hormone, resulting in a decrease in testosterone levels and impaired spermatogenesis. Additionally, CP exerts its cytotoxic effects by inhibiting the proliferation and differentiation of germ cells, leading to a decrease in sperm production. It also affects Leydig cells, which are responsible for the production of testosterone, thus decreasing testosterone levels. In conclusion, CP exhibits potent cytotoxic properties that not only affect cancer cells but also severely damage male gonadal functions. The mechanisms involved in CP-induced gonadal toxicity include oxidative stress and disruption of the hypothalamic-pituitary-gonadal axis. Therefore, it is crucial to consider the potential gonadal toxicity of CP when prescribing it for cancer treatment and to closely monitor the gonadal functions of male patients receiving CP therapy.

High-throughput proteomics has become an exciting field and a potential frontier of modern medicine since the early 2000s. While significant progress has been made in the technical aspects of the field, translating proteomics to clinical applications has been challenging. This review summarizes recent advances in clinical applications of high-throughput proteomics and discusses the associated challenges, advantages, and future directions. We focus on research progress and clinical applications of high-throughput proteomics in breast cancer, bladder cancer, laryngeal squamous cell carcinoma, gastric cancer, colorectal cancer, and coronavirus disease 2019. The future application of high-throughput proteomics will face challenges such as varying protein properties, limitations of statistical modeling, technical and logistical difficulties in data deposition, integration, and harmonization, as well as regulatory requirements for clinical validation and considerations. However, there are several noteworthy advantages of high-throughput proteomics, including the identification of novel global protein networks, the discovery of new proteins, and the synergistic incorporation with other omic data. We look forward to participating in and embracing future advances in high-throughput proteomics, such as proteomics-based single-cell biology and its clinical applications, individualized proteomics, pathology informatics, digital pathology, and deep learning models for high-throughput proteomics. Several new proteomic technologies are noteworthy, including data-independent acquisition mass spectrometry, nanopore-based proteomics, 4-D proteomics, and secondary ion mass spectrometry. In summary, we believe high-throughput proteomics will drastically shift the paradigm of translational research, clinical practice, and public health in the near future.

Information on the survival of urothelial cancer (UCa) patients with brain metastases (BM) is largely unreliable due to the rarity of such cases. Previous studies that have attempted to capture the prevalence and survival of these patients are limited to case series and retrospective studies with small cohort sizes. This study aimed to explore patient characteristics and treatment outcomes based on treatment modalities from a large sample of patients with UCa and BM.

In this retrospective study, we utilized the TriNetX Research Network, a real-world and in-house database with longitudinal electronic medical records from 92 institutions. The database was queried for patients with UCa who also had BM. Kaplan–Meier plots were used to assess overall survival (OS). Log-rank tests were applied for stratified outcomes. The Cox proportional hazards model was used for continuous data.

We identified 357 patients with UCa and BM, representing 4.7% of the 7,521 patients diagnosed with primary UCa. The mean age at diagnosis was 65.6 years, with a predominance of male patients (67%). The median OS from BM diagnosis was 18.6 months. For patients treated solely with stereotactic radiosurgery (SRS), the median OS was 20.8 months. For those treated with both SRS and surgical resection, the median OS was 18.6 months. There was no significant difference in survival between patients treated with SRS alone and those treated with both SRS and surgical resection (p = 0.875). For patients treated only with gemcitabine chemotherapy, the median OS was 15.4 months.

This study represents the largest known retrospective analysis of UCa patients with BM. Survival trends for patients treated with surgical resection, SRS, and systemic therapies are described in detail.

Splenic venous hypertension or left-sided portal hypertension is a rare condition caused by an obstruction of the splenic vein. Usually, it presents with upper gastrointestinal bleeding in the absence of liver disease. Etiologies can be classified based on the mechanism of development of splenic vein hypertension: compression, stenosis, inflammation, thrombosis, and surgically decreased splenic venous flow. Diagnosis is established by various imaging modalities and should be suspected in patients with gastric varices in the absence of esophageal varices, splenomegaly, or cirrhosis. The management and prognosis vary depending on the underlying etiology but generally involve reducing splenic venous pressure. The aim of this review was to summarize the etiologies of splenic venous hypertension according to the mechanism of development.

Since its proposal, the Model for End-Stage Liver Disease (MELD) score has been employed to predict short-term mortality among patients with chronic liver disease and those awaiting liver transplantation, serving as the primary criterion for organ allocation. However, as the demographic and epidemiological characteristics of chronic liver disease and liver transplantation have evolved, a range of MELD-related scores has emerged, including MELD-Na, iMELD, delta MELD, MELD XI, MELD-LA, and pediatric end-stage liver disease, culminating in the recently proposed MELD 3.0, which builds upon MELD-Na. This study aimed to comprehensively review and summarize relevant studies on MELD 3.0 in various scenarios, assessing its effectiveness in organ allocation, post-transplantation outcomes, and mortality prediction for patients with end-stage liver disease. Our preliminary findings indicate superior predictive performance of MELD 3.0, warranting further in-depth investigations to broaden its clinical implications.

Early detection of hepatocellular carcinoma (HCC) is crucial for improving survival in patients with chronic hepatitis. The GALAD algorithm combines gender (biological sex), age, α-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC detection. Similarly, the GAAD algorithm incorporates gender (biological sex), age, AFP, and PIVKA-II. This study aimed to assess the clinical utility of AFP-L3 in the GALAD algorithm and its potential synergies with ultrasound. We compared the clinical performance of GALAD with GAAD; AFP; AFP-L3; and PIVKA-II, with or without ultrasound, in Taiwanese adults.

A total of 439 serum samples were analyzed using a Cobas® e 601 analyzer (healthy controls, n = 200; chronic liver disease controls, n = 177; HCC cases, n = 62). Performance was assessed through receiver operating characteristic curve analyses to calculate the area under the curve.

The area under the curve for differentiating early-stage HCC from patients with chronic liver disease was optimal for PIVKA-II (84.9%), GAAD (79.8%), and GALAD (79.4%), with slightly improved performance for detecting all-stage HCC. Clinical performance was unaffected by disease stage or etiology. Sensitivity for early-stage HCC was highest for GAAD (57.6%) and GALAD (57.6%). Sensitivity for each strategy was further enhanced when combined with ultrasound, regardless of disease stage or etiology (P < 0.01).

These findings indicate that the role of AFP-L3 in the GALAD algorithm is minimal, supporting the use of GAAD for HCC detection. A combination of GAAD, GALAD, or PIVKA-II with ultrasound may improve diagnostic efficiency compared with recommended strategies.

Fine needle aspiration cytology (FNAC) is a cost-efficient technique for the management of thyroid nodules. Changes in the World Health Organization classification of thyroid tumors can influence reliability of cytology. The 2023 Bethesda System for Reporting Thyroid Cytopathology has adapted cytological nomenclature to these changes. The aim of this paper was to analyze the management of atypia of undetermined significance (AUS) in our institution.

Retrospective review of thyroid FNAC diagnosed with AUS in a single hospital between 2014 and 2022. We analyzed the management of patients and the risk of malignancy associated with AUS.

AUS represented 7.5% of all thyroid FNAC diagnoses (273 patients). In 74.1% of the patients, FNAC was repeated, and 54.9% of the lesions were downgraded. Surgical resection of the nodule was performed in 38.2% of the patients, mostly after a repeat FNAC with upgrading. Ninety-one percent of the patients downgraded in the repeat FNAC did not undergo surgery. The risk of malignancy of the AUS category after repeat FNAC was 26.1%. AUS diagnosis was due to nuclear atypia in 32% of the patients, and we found a significant association between nuclear atypia and upgrading in repeat FNAC. Of the 96 patients who underwent surgery in our series, 42 had malignant lesions, including noninvasive follicular thyroid neoplasms with papillary-like features.

The clinical management of AUS patients includes repeat FNAC, which is strongly correlated with the risk of malignancy. Nuclear atypia seems to be more predictive of malignancy than architectural patterns.

A mental disorder, also referred to as a psychiatric disorder or mental illness, is characterized by significant disturbances in an individual’s thinking, emotions, or behavior. In Ayurveda, herbal plants are used as alternative therapies for various ailments, including mental disorders. This review aims to provide a comprehensive overview of herbal medicines used in treating mental disorders in Sri Lanka. It relies on foundational books as primary sources to systematically identify and analyze the therapeutic potential of 24 traditional medicinal plants for treating mental disorders. Each plant was evaluated based on its scientific name, plant parts used, distribution in Sri Lanka, mechanisms of action, and identified phytochemicals. Furthermore, additional research was conducted using keywords such as mental disorders, herbal plants, plant distribution, phytochemicals, side effects, and mechanism of action through scientific databases. The phytochemicals present in these herbal plants possess antioxidant, anti-inflammatory, and neuroprotective properties, contributing to their potential antipsychotic activities. Trigonelline (from Abrus precatorius), bacosides (from Bacopa monnieri), asiaticoside and asiatic acid (from Centella asiatica), quercetin (from Ginkgo biloba), alliin and allicin (from Allium sativum), luteolin-7-O-glucoside (from Eclipta alba), and shogaol (from Zingiber officinale) demonstrate significant potential in modulating neurotransmitter levels, reducing oxidative stress, and alleviating symptoms associated with mental disorders such as depression, anxiety, and neurodegenerative diseases. The suggested therapeutic value of these identified herbal plants and their bioactive phytochemicals indicates the need for preserving and extensively investigating these remedies to establish their clinical effectiveness.

Visualization of the spatiotemporal organization and dynamics of the genome in the nucleus is essential to elucidate how chromatin structure and nuclear function are intertwined. In the past, such studies were limited by the lack of appropriate tools. However, various imaging techniques now allow direct visualization of genomic loci in living cells. One of the main drivers behind this progress is the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) technology. Initially used as an efficient and specific genome editing tool, the versatility of the CRISPR/Cas system has rapidly expanded its application range to include diagnostics, therapeutics, and, more recently, live cell imaging. In contrast to traditional fluorescent in situ hybridization, CRISPR/Cas-based imaging systems enable real-time dynamic tracking of genomic sequences down to the level of single cells and even a single locus. Recognizing the vital role played by CRISPR/Cas-based imaging systems in advancing our understanding of genome function in relation to its spatiotemporal organization, this review aimed to depict the current landscape of CRISPR/Cas-based technologies in genomic imaging. It discusses the principles, notable features, advantages, and limitations of these CRISPR/Cas-based imaging systems and concludes with a brief outlook into the future.