VIPoma is a rare pancreatic neuroendocrine tumor characterized by the overproduction of vasoactive intestinal peptide (VIP), typically manifesting as watery diarrhea, hypokalaemia and metabolic acidosis. Its presentation can be atypical, complicating diagnosis. We report the case of a 30-year-old male who initially presented with obstructive jaundice and fatigue, with imaging revealing a pancreatic head mass and liver metastases. Histopathological analysis confirmed a lowgrade pancreatic neuroendocrine tumor. The clinical course was complicated by portal vein thrombosis and metastatic spread. Six months later, the patient developed persistent, refractory watery diarrhea with associated hypokalaemia. Elevated serum VIP levels and Gallium-68 DOTATATE positron-emission tomography and computed tomography (PET-CT) supported the diagnosis of VIPoma. Symptom resolution was achieved with subcutaneous octreotide, followed by transition to monthly long-acting release (LAR) octreotide. Approximately 60% of VIPoma cases are metastatic at the time of diagnosis, as demonstrated in this patient. The case highlighted the diagnostic challenges of VIPoma in the presence of atypical symptoms such as jaundice and absence of initial diarrhea. It also underscores the need for close multidisciplinary collaboration to determine the best course of action and to optimize patient outcomes.

The hypothalamic-pituitary-gonadal (HPG) axis coordinates reproductive function and incorporates gonadal sex steroid feedback to regulate gonadotropin secretion in a homeostatic manner. In females, ovarian estrogens and progestins act as the primary negative feedback signals to suppress luteinizing hormone (LH) release, whereas in males, androgens, such as testosterone (T), typically provide this feedback. However, androgens can also exert feedback effects on the female HPG axis, particularly in conditions where circulating T levels exceed that of the normal female physiological range. Three clinically relevant examples are anabolic substance abuse, testosterone therapy, and polycystic ovary syndrome (PCOS; recently renamed polyendocrine metabolic ovarian syndrome [PMOS]). Despite shared exposure to "androgen excess," these different hyperandrogenic states are associated with strikingly different neuroendocrine phenotypes. In testosterone therapy and anabolic substance abuse, high exogenous androgen exposure in or above the male physiological range typically suppresses LH secretion and disrupts ovulatory cycling, mimicking enhanced negative feedback on the HPG axis. Conversely, in PMOS, endogenous elevations in T, high for a female but below the male physiological range, are associated with increased LH secretion, acyclicity, and anovulation. The mechanisms underlying these divergent LH outcomes remain unclear but may reflect, in part, differences in the source of androgens (exogenous vs. endogenous), circulating androgen concentrations, and development timing and/or duration of androgen exposure. This review synthesizes current clinical and preclinical evidence to compare distinct models of hyperandrogenemia with respect to the female HPG axis and aims to illuminate how endogenous and exogenous androgens with different features differentially alter female neuroendocrine function.

Circulating tumor DNA (ctDNA) serves as a non-invasive liquid biopsy technique, offering potential utility in the prognostic evaluation of multiple myeloma (MM). In this study, we performed a systematic review and updated meta-analysis to analyze the association between ctDNA and the prognosis of patients diagnosed with MM. A comprehensive literature search was performed across PubMed, Embase, Web of Science, and the Cochrane Library to retrieve relevant literature published up to May 29, 2025, assessing the impact of ctDNA on survival outcomes in patients with MM. The survival outcomes included overall survival (OS), progression-free survival (PFS), and time to progression (TTP). A total of 948 MM patients from 14 studies were included in the analysis. Patients with detectable ctDNA exhibited a significantly increased risk of aggressive disease progression (hazard ratio [HR], 3.21; 95% confidence interval [CI], 1.98-5.18) and reduced OS (HR, 3.97; 95% CI, 2.24-7.04). Subgroup analyses consistently indicated that ctDNA positivity was associated with accelerated disease progression, irrespective of race, disease status, treatment, or ctDNA detection method. In subgroups defined by relapsed or refractory MM (RRMM) and Oceanian or Caucasian race, ctDNA positivity was significantly correlated with poorer OS. However, the associations were not significant in newly diagnosed MM (NDMM) or among Asian patients. Therefore, we conclude that ctDNA is a potential predictor of inferior survival outcomes in MM patients.

Neurosyphilis may present with a variety of clinical symptoms and neuroimaging findings and is thus likely to be overlooked. We report a case of neurosyphilis presenting with dementia, limbic encephalitis, and normal pressure hydrocephalus.

A 47-year-old man had gradually experienced cognitive decline for over a year. He was admitted to a psychiatric hospital. Brain computed tomography imaging showed ventricular enlargement. Serological tests for syphilis were positive. He was transferred to our hospital, where he exhibited gait disturbance, cognitive impairment, and urinary incontinence. Brain magnetic resonance imaging showed high signal intensity in both medial temporal lobes. Treponemal cerebrospinal fluid testing was positive. He was treated with intravenous benzylpenicillin for 36 days and two courses of intravenous methylprednisolone pulse therapy. His psychomotor agitation required physical restraint for 37 days and treatment with risperidone. Although his gait disturbance and urinary incontinence improved, no clinically meaningful change in cognitive impairment was observed. The high signal intensity on repeat imaging was attenuated. He was transferred back to the psychiatric hospital 3 months after admission.

This case of neurosyphilis was characterized by early-onset dementia with limbic encephalitis and normal pressure hydrocephalus. Psychiatrists should be aware of the possibility of neurosyphilis in such cases.

Cervical cancer management relies heavily on magnetic resonance imaging (MRI) for staging and treatment planning; however, manual segmentation is time-consuming and prone to variability. This systematic review aimed to evaluate the performance and clinical potential of machine learning (ML) and deep learning (DL) algorithms for automated cervical cancer segmentation on MRI.

A systematic review guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (PROSPERO: CRD420251247441) was conducted by searching PubMed/MEDLINE, Embase, Scopus, Web of Science, IEEE Xplore, and Google Scholar until December 2025. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). MRI-based segmentation studies were primarily included, while computed tomography (CT)- and positron emission tomography (PET)-based multimodal studies were analysed as complementary evidence. Due to substantial heterogeneity, findings were synthesized narratively, and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.

Thirty studies were included, mainly evaluating segmentation of tumours, high-risk clinical target volumes, and organs at risk. DL models, particularly U-Net variants, convolutional neural networks, and transformer-based architectures, demonstrated promising performance, with reported Dice similarity coefficients ranging from 0.60 to 0.93. However, performance varied according to target structure, tumour characteristics, and imaging protocols. Overall risk of bias showed "some concerns," mainly due to patient selection, reference standards, and limited external validation. GRADE assessment indicated low certainty of evidence due to heterogeneity, methodological limitations, and imprecision.

ML and DL algorithms show promising potential for automated cervical cancer segmentation on MRI, with potential benefits for efficiency and reproducibility. However, further multicenter studies with standardized protocols and external validation are required before routine clinical implementation.

PRISMA guidelines and was prospectively registered in PROSPERO: CRD420251247441.

Abnormal DNA hypermethylation mediated by DNA methyltransferases (DNMT) is a nearly universal hallmark of human cancers. However, while DNA methyltransferase inhibitors (DNMTi) such as decitabine and azacitidine are effective in treating myelodysplatic syndrome/leukemia, they have had limited utility for the majority of other cancers. Through a chemical library screen, we identify that triptolide, a diterpenoid epoxide from Tripterygium wilfordii, and multiple of its analogs, significantly augment the epigenetic and anti-cancer effects of decitabine in vitro and in vivo. These effects are attributable to inhibition of DCTPP1-mediated cleavage of 5-aza-deoxycytidine triphosphate, the convergent activated metabolite of nucleoside DNMTi, leading to enhanced drug incorporation into genomic DNA, increased DNMT degradation, enhanced DNA demethylation and associated transcriptional reprogramming. We show that high DCTPP1 expression mediates cell-intrinsic resistance to nucleoside DNMTi, and that triptolide and its analogs could overcome this resistance. These findings nominate combining DNMTi with triptolide or its analogs as a rational cancer therapeutic strategy.

Hepatocellular carcinoma (HCC) exhibits a suboptimal response to immune checkpoint blockade (ICB) therapy; to overcome this resistance, we aimed to delineate key immune resistance factors via multi-omics analysis, develop strategies to block their immunosuppressive axes, and engineer a targeted nanosystem to enhance immunotherapy efficacy against PD-1 resistance in HCC. Using transcriptomic and proteomic data from anti-PD-1-treated HCC patients, along with functional validation in murine models and mechanistic molecular and cell biology studies, we identified transketolase-like 1 (TKTL1) as a dual-nature biomarker where overexpression predicted poor baseline prognosis yet enhanced response to ICB. Mechanistically, TKTL1 diverts glucose flux into glycolysis rather than pentose phosphate pathway (PPP), recruiting USP9X to deubiquitinate and stabilize HIF-1α, which upregulates HK2 to amplify glycolytic output and lactate accumulation. This metabolic rewiring orchestrates dual immunosuppressive circuits through HIF-1α-driven CCL4 secretion recruiting PD-L1^high dendritic cells (DCs), coupled with lactate-induced TRIM28^K408 lactylation that stabilizes PD-L1 by blocking ubiquitin-mediated degradation. We engineered a hepatoma-membrane-coated MnO₂ nanosystem (CQLH) co-delivering a TKTL1 inhibitor and lactate oxidase, which disrupted the TKTL1-HIF-1α-HK2 axis, depleted lactate, and reprogrammed the tumor microenvironment, thereby enhanced anti-PD-1 therapy to suppress tumor growth, especially in TKTL1^high tumors. These findings define a critical "TKTL1-glycolysis-lactate-DC" axis driving anti-PD-1 sensitivity in HCC, position TKTL1 as both a potential biomarker for ICB response and a tractable therapeutic target, and demonstrate that the targeted CQLH nanosystem overcomes resistance and enhances anti-PD-1 efficacy, offering a precision immunotherapeutic strategy for TKTL1^high HCC.

Surgery is the main treatment for dentigerous cysts. Although the treatment concept has shifted from radical lesion removal to function‑preserving strategies, surgical trauma and related risks are still hard to avoid completely. The strategy of spontaneous fenestration may be preferred in a few dentigerous cysts in children.

A 6-year-old boy was referred because of the delayed eruption of a left mandibular posterior tooth. Panoramic radiographic examination revealed a well-defined radiolucent area measuring approximately 22 × 18 mm around the crown of the left mandibular first permanent molar (tooth 36), which was vertically impacted at Nolla stage 7 and extended to the distal root of the left mandibular second primary molar. A dentigerous cyst of tooth 36 was diagnosed. Because the tooth 36 presented eruptive potential and no obvious coronal bony barrier, only regular follow-up was adopted. At 6‑month follow‑up the cyst decreased to about 16 × 11 × 14 mm on CBCT。After two years, tooth 36 had erupted spontaneously and the cyst had completely resolved.

The tooth 36 had an immature root with no bony obstruction coronally and a small-to-medium cyst volume and lack of adverse effects, and thus conservative monitoring was adopted. During follow-up, the cyst progressively decreased in size and the affected tooth showed a clear tendency for occlusal eruption, ultimately resulting in complete resolution of the cyst and spontaneous eruption of the tooth, confirming that this strategy may be a feasible option. We also reviewed relevant literature and analyzed the underlying mechanisms, providing evidence for more conservative clinical management strategy of dentigerous cysts in children.

The malignant progression of nonsmall cell lung cancer (NSCLC) is closely related to cancer stemness. Histone deacetylase 4 (HDAC4) plays a regulatory role in lung cancer, but its effect on NSCLC stemness remains unclear. This study aimed to investigate the role and mechanism of HDAC4 in NSCLC stemness.

In this study, a tumor-bearing model was established by subcutaneously injecting A549 cells into the right dorsal side of nude mice. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), Western blotting, and immunohistochemistry were used to measure gene and protein expression levels. Flow cytometry, sphere formation assays, and Transwell experiments were employed to assess cancer cell stemness, migration, and invasion. Additionally, a kit was used to measure changes in glutamine metabolism-related indicators.

In this study, we found that knocking down HDAC4 expression inhibited the expression of SRY-box transcription factor 2 (SOX2), octamer-binding transcription factor 4 (OCT4), and nanog homeobox (NANOG) in A549 cells; it also reduced the proportions of CD133- and CD44-positive cells and suppressed their sphere formation, cell migration, and invasion abilities. Furthermore, HDAC4 knockdown inhibited glutamine uptake, glutamate production, α-ketoglutarate levels, and glutaminase (GLS) activity. Notably, treatment with the additional glutamine metabolism inhibitor CB-839 attenuated the promoting effects of HDAC4 overexpression on the stemness, migration, and invasion of A549 cells. In addition, HDAC4 promoted the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and solute carrier family 38 member 2 (SLC38A2); after overexpressing HIF-1α, the inhibitory effect of HDAC4 knockdown on SLC38A2 expression in A549 cells was weakened.

Our study reveals a critical mechanism by which HDAC4 enhances glutamine metabolism through upregulation of HIF-1α expression to promote SLC38A2 expression, thereby driving NSCLC stemness and progression.

Triple-negative breast cancer (TNBC) has poor outcomes and few effective treatments, partly because of epigenetic heterogeneity. We show that the heterochromatin mark H4K20me3 is more variable than H3K9me3 across normal and malignant breast tissues, and that H4K20me3-enriched regions are linked to more open chromatin and active transcription. Pharmacologic inhibition of the H4K20me3 methyltransferases KMT5B and KMT5C with A-196 decreases H4K20me3 and increases H4K20me1 at loci involved in lineage identity, stress responses, and the cell cycle. A-196 suppresses tumor growth in vivo while promoting mesenchymal features and the unfolded protein response (UPR). Multi-omic profiling shows that mesenchymal TNBCs have the lowest H4K20me3 levels and the greatest sensitivity to UPR stress. In basal TNBC, KMT5B&5 C inhibition drives mesenchymal transition and elevated endoplasmic reticulum stress-associated growth arrest via E2F4. Combining A-196 with the HSP90, IRAK4 inhibitors, or STING agonist synergistically reduces TNBC tumor growth. These findings nominate KMT5B&5C as promising therapeutic targets in TNBC.