Febrile neutropenia (FN) is one of the acute and serious complications of chemotherapy-induced myelosuppression in tumor patients. Antibiotics and granulocyte colony-stimulating factor are the mainstays of its treatment. However, this therapy still faces many challenges and may trigger drug resistance, as well as adverse effects such as bone pain and vasculitis. How to minimize treatment-related toxicity while ensuring therapeutic efficacy has become a key issue to be addressed in current clinical practice. In recent years, traditional Chinese medicine (TCM) has demonstrated unique advantages in the prevention and treatment of FN. We conducted a comprehensive search of the PubMed, Web of Science, and CNKI databases using keywords such as TCM and FN, covering the period from their establishment to May 2025. Clinical studies have shown that the combination of TCM and modern medicine can significantly reduce the incidence of FN, while also enhancing the number of granulocytes, shortening the duration of fever, improving the quality of life of patients, and reducing other toxic effects of chemotherapy. These results suggest that TCM is a promising and safe complementary therapy. However, more high-quality trials are needed to verify its benefits. This review summarizes the latest progress in the treatment of FN with TCM and discusses future development directions.

Artificial intelligence (AI) translation in genitourinary (GU) pathology has progressed unevenly across organs and tasks. This review addresses a central clinical question: which GU pathology AI applications are deployment-ready, which require further validation, and what frameworks can guide safe implementation? We synthesize evidence across GU organs and introduce pragmatic translation frameworks to guide deployment and prioritize translational research.

Narrative review integrating foundational literature with targeted 2023–2025 publications, emphasizing regulatory milestones, external validation, and prospective studies. Literature was identified through PubMed, Embase, and conference proceedings using structured search terms for AI, digital pathology, and GU organ-specific queries. For each organ/task, we mapped evidence strength, regulatory maturity, generalizability, workflow integration, safety, and feasibility to a Translational Readiness Index (TRI) rubric (0–30 scale).

Prostate biopsy AI demonstrates the strongest maturity (TRI 26/30), supported by U.S. Food and Drug Administration-cleared systems, multi-site validation, and prospective implementations showing efficiency gains and reduced ancillary testing. Bladder cytology shows moderate readiness (TRI 19/30), with commercial offerings supporting pilotable prescreening workflows aligned with the Paris System when paired with uncertainty-aware deferral. Bladder histology, renal neoplasia, and low-prevalence domains (testis, penis) remain emerging (TRI 6–15/30), constrained by label variability, rare subtype underrepresentation, and limited external validation.

The TRI rubric, SURE-Path safety bundle, and VALIDATED/ORCHESTRATE implementation pathway provide a practical template for evidence-based deployment in GU pathology. Clinically defensible translation requires matching intended use to validation evidence, with explicit safeguards for emerging applications.

Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection leads to severe systemic inflammation, increasing non-AIDS morbidity and mortality risk. CD39 ectoenzyme on T-cells, which catalyzes the conversion of pro-inflammatory purines to immunosuppressive adenosine, plays an important role in inflammation control. The role of CD39+ T-cells in systemic inflammation during HIV/HCV coinfection under antiretroviral therapy (ART) remains unexplored. This study aimed to identify specific patterns of CD39 expression on T-cells in ART-treated HIV/HCV coinfected patients and assess their relationship with systemic inflammation.

We conducted a case-control study that enrolled 41 HIV/HCV coinfected patients on stable ART (cases) and 23 healthy controls. CD39 expression on blood CD4+ and CD8+ T-cells, including CD45RA+ and CD45RA– subsets, was quantified using flow cytometry. Cytokines were assessed using multiplex and enzyme-linked immunosorbent assays.

A significant proportion of CD4+ T-cells expressed CD39 in both groups (cases – 24.0%; controls – 16.1%). That was not true for CD8+ T-cells (cases – 3.2%; controls – 2.8%). CD39 expression was higher on CD45RA+ than CD45RA– CD4+ T-cells (cases – 39.4% vs. 19.0%; controls – 24.6% vs. 9.2%). HIV/HCV coinfected patients exhibited a significantly increased proportion of CD39+ CD4+ T-cells compared to uninfected controls (P < 0.01). A negative correlation was observed between the percentage of CD39+ CD4+ CD45RA– T-cells and levels of pro-inflammatory chemokines monocyte chemoattractant protein 1 (R = –0.392; P < 0.01) and eotaxin (R = –0.325; P < 0.05).

The data suggest a compensatory expansion of cells with regulatory properties that is ultimately insufficient to control systemic immune activation.

Perioperative anaphylaxis is a rare, life-threatening, iatrogenic condition that predominantly arises following anesthesia. The unique context of this condition, characterized by the concurrent administration of multiple drugs, patient draping, and altered physiological states, presents significant diagnostic and therapeutic challenges, contributing to a higher mortality rate compared to anaphylaxis in other settings. This narrative review synthesizes the evidence to delineate the evolving etiology, pathophysiology, atypical clinical presentation, evidence-based immediate management, and strategic prevention of perioperative anaphylactic reactions. The primary causative agents include neuromuscular blocking agents, antibiotics, and latex, with emerging culprits such as chlorhexidine, dyes, and novel agents like remimazolam. Diagnosis is complicated by the paucity of cutaneous signs; thus, cardiovascular collapse combined with a low end-tidal carbon dioxide level has emerged as a useful supportive diagnostic indicator that requires integration with the clinical context. Immediate management prioritizes the prompt administration of epinephrine and aggressive fluid resuscitation. Subsequent allergological investigations, primarily via skin testing and serum tryptase/histamine measurement, are paramount for identifying the causative agent and preventing its recurrence. Prevention strategies emphasize meticulous history-taking, risk stratification, and the creation of latex-free environments. Future directions must focus on establishing global surveillance networks, exploring novel biomarkers and risk factors such as the circulating microbiome—a preliminary but promising area of research—and enhancing team preparedness through simulation training to improve patient safety outcomes.

As the leading cause of chronic liver disease globally, metabolic dysfunction-associated steatotic liver disease (MASLD) lacks effective therapies. This study aimed to investigate the therapeutic potential and molecular mechanisms of oxytocin (OXT) in MASLD.

Integrated bioinformatics analysis of MASLD datasets was carried out to identify OXT-related metabolic disturbances. Serum OXT levels were quantified using an enzyme-linked immunosorbent assay in 113 MASLD patients and 63 healthy controls. Mechanistic assays were conducted using oleic acid (OA)-induced, lipid-loaded HepG2 cells and high-fat diet-fed C57BL/6 mice, and OXT was administered intraperitoneally in vivo and supplemented in vitro.

Bioinformatics analysis revealed significant changes in OXT expression levels, particularly in fatty acid metabolism. Elevated OXT expression levels in MASLD patients were identified as an independent prognostic factor. In vitro, OXT significantly reduced OA-induced lipid accumulation in HepG2 cells, while in vivo, it decreased body weight, liver injury, and serum cholesterol levels in high-fat diet-fed mice. Mechanistically, OXT enhanced the expression level of phosphorylated AMP-activated protein kinase (AMPK) and suppressed the levels of sterol regulatory element-binding protein-1c (SREBP1c) and fatty acid synthase (FAS). Blockade of AMPK with the chemical inhibitor Compound C reversed the ability of OXT to suppress the SREBP1c/FAS axis and reduce lipid accumulation in hepatocytes. Additionally, OXT inhibited the nuclear translocation of SREBP1c in OA-treated cells.

The findings demonstrate that OXT may serve as a potential therapeutic agent for MASLD by regulating the AMPK/SREBP1c/FAS pathway in lipid metabolism.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and sarcopenia frequently coexist, yet their causal relationship and underlying mechanisms remain poorly defined. This study aimed to investigate whether a bidirectional causal link exists between MASLD and sarcopenia and to identify the molecular mediators involved in liver-muscle crosstalk.

We applied Mendelian randomization to test the causal effect of sarcopenia-related traits on MASLD risk. To capture distinct clinical features, we established complementary mouse models, including diet-induced and genetic (ob/ob) MASLD models, a stelic animal model, and a drug-induced muscle atrophy model. Multi-tissue transcriptomic profiling was performed on liver and muscle to uncover altered pathways.

Complementing prior genetic evidence establishing MASLD as a causal factor for sarcopenia, our Mendelian randomization analysis revealed that diminished muscle mass and muscle function contribute to an elevated risk of MASLD. In mice with MASLD, we observed loss of muscle mass, reduced strength, and ectopic lipid deposition in skeletal muscle. Conversely, muscle atrophy exacerbated hepatic steatosis, inflammation, and fibrosis in MASLD mice. Transcriptional profiling revealed that sarcopenia impairs hepatic metabolic homeostasis by enhancing fatty acid uptake and impairing oxidative phosphorylation, while MASLD, in turn, promotes muscle dysfunction by exacerbating inflammatory responses and metabolic dysfunction. We further identified C-C motif chemokine ligand 2 as a key myokine that drives MASLD, and adrenomedullin as a key hepatokine that triggers sarcopenia.

Our findings suggest a potential bidirectional causal relationship between MASLD and sarcopenia, which may be partially mediated by C-C motif chemokine ligand 2 and adrenomedullin.

The incidence and mortality of stroke are gradually increasing. In this context, post-stroke neuronal loss and the related long-term complications, along with costly treatment strategies, are significant concerns for healthcare professionals, and effective, convenient, and inexpensive therapeutic modalities are required. Natural and easily accessible herbal remedies may be the optimal option in post-stroke recovery. This narrative review aims to summarize the neuroprotective properties of Withania somnifera (Ashwagandha) and its therapeutic efficacy in neuronal plasticity and recovery after stroke. Original research articles, reviews, and case studies were sourced from databases such as PubMed, Web of Science, Scopus, Google Scholar, Medline, and Embase. Only full articles published in English up to July 2025 were considered. Keywords including W. somnifera, Ashwagandha, stroke, cerebral ischemia, neurodegeneration, neuronal loss, and post-stroke recovery were utilized for the literature search. It has been found that various plant parts of W. somnifera are abundant in bioactive compounds. The neuroprotective effects of W. somnifera are documented in numerous diseases. Nevertheless, W. somnifera is reported to be involved in modulating various biological pathways to mitigate neuroinflammation, apoptosis, and oxidative stress in stroke. W. somnifera promotes cell proliferation and enhances neurogenesis. Preclinical experiments on murine models show the effectiveness of W. somnifera in post-stroke recovery by enhancing neural plasticity and reducing neuronal loss in the infarct area. Furthermore, W. somnifera boosts neurotransmitter levels, improves motor functions, and enhances memory. It also decreases neutrophil infiltration in the infarct region and lessens neuronal loss. Therefore, the application of W. somnifera may prove advantageous in facilitating post-stroke recovery by enhancing neural function. However, well-designed clinical trials are needed to confirm the efficacy of W. somnifera in post-stroke recovery in humans.

The bromodomain and extra-terminal domain (BET) protein family, particularly BRD4, is critical for the control of oncogenic transcriptional programs in solid tumors. Although initial-generation BET inhibitors, such as JQ1, molibresib, and birabresib, have demonstrated preclinical efficacy in repressing MYC-dependent pathways, their clinical translation has been hampered by low monotherapy activity, pharmacokinetic heterogeneity, and dose-limiting toxicities. This review aims to update the mechanistic foundations, clinical trial results, and development of therapeutic approaches to BET inhibition in solid tumors, outlining its evolving role in the next generation of cancer treatment strategies. Various clinical trials in different phases have demonstrated heterogeneous responses among solid tumor types, with greater effects in NUT carcinoma and castration-resistant prostate cancer. Resistance mechanisms, including BRD4 isoform switching and compensatory signaling activation, emphasize the need for advanced and innovative BET-targeting modalities. BD2-selective BET inhibitors and proteolysis-targeting chimeras are likely to overcome these limitations by increasing target specificity and reducing systemic side effects. In addition, combination strategies, such as PARP inhibitors, AR antagonists, and immune checkpoint blockade, have synergistic potential to augment anticancer activity. In conclusion, this review provides a comprehensive overview of the advances, challenges, and future directions of BET bromodomain inhibition in solid tumors.

DNA polymerase epsilon catalytic subunit A (POLE) gene plays a crucial role in DNA repair and chromosomal replication. Mutations in the POLE gene have been linked to cancer, particularly colorectal carcinoma (CRC). However, the genomic landscape and pathological significance of POLE mutant CRC remain underreported. This study aimed to characterize the clinicopathologic features and genomic landscape of CRC harboring POLE mutations and to investigate the implications of co-occurring genetic alterations.

We identified thirty-four CRC cases with POLE mutations from our institution’s database using the next-generation sequencing gene panels including 161-gene panel for the cases of 2016–2021 and the 505-gene panel for the case of 2022–2023. We collected clinicopathologic data (age, sex, tumor site, and grading) and conducted comprehensive next-generation sequencing. Survival outcomes were assessed by reviewing patients’ medical records at the time of data collection, with survival status determined based on the most recent clinical follow-up available with overall survival as the primary endpoint and a median follow-up time of 20.5 months. Statistical analyses, including chi-squared testing and CoMutation plotting, were performed using Python.

The enrolled 34 patients had a median age of 60.5 years (range: 37–84); tumors were in the colon (26 cases, 77%) and rectum (8 cases, 23%), with a mismatch repair deficiency rate of 29%. Next-generation sequencing analysis of a 505-gene panel revealed that POLE mutations were predominantly missense (89%). The mutations were distributed across various domains: 11.4% in the exonuclease domain, 25.7% in the catalytic domain, 20% in an unknown functional domain, and 42.9% in a nonfunctional domain. The average number of genomic mutations per case was 12.1 ± 12.3. CoMutation analysis identified two subsets: genomic mutation high (>5 mutations, range 6–60 mutations, n = 22) and mutation low (. Notably, TP53 mutations occurred in 55% of cases, and defects in double-stranded DNA repair proteins occurred in 47% of cases. POLE mutant CRC with co-occurring DNA repair mutations exhibited a significantly higher total number of genomic mutations (19.9 ± 14.4, range 7–60 mutations; chi-squared = 5.1, p-value = 0.02). Although a survival comparison between TP53 wild-type and TP53 mutant subgroups of POLE-mutant CRC is not statistical significant (p = 0.37), it showed a trend toward better survival in the TP53 wild-type group.

Our findings reveal unique genomic landscapes in POLE mutant CRC, particularly with co-occurring TP53 or double-stranded DNA repair mutations, which are critical in colorectal carcinogenesis. These tumors demonstrate increased genetic instability, highlighting potential for immunotherapy.