Spermatogenesis is a highly ordered and spatiotemporally regulated developmental process in the male reproductive system, during which spermatogonial stem cells (SSCs), supported by the seminiferous tubule microenvironment, sequentially undergo mitosis, meiosis, and spermiogenesis to ultimately generate structurally intact spermatozoa. This complex process is accompanied by extensive transcriptional reprogramming, chromatin remodeling, and finely tuned post-transcriptional regulation. Precise control of RNA fate is therefore essential for maintaining the continuity and fidelity of spermatogenesis, and its disruption represents a major molecular basis of male infertility. N⁶-methyladenosine (m⁶A), the most abundant internal RNA modification in eukaryotes, has emerged as a critical regulator of post-transcriptional gene expression. m⁶A methyltransferases (“writers”) catalyze the addition of a methyl group to the N⁶ position of adenosine, m⁶A demethylases (“erasers”) remove the modification, and m⁶A-binding proteins (“readers”) recognize m⁶A-modified transcripts. Through the coordinated actions of these factors, m⁶A regulates transcript fate at multiple levels, including RNA splicing, nuclear export, stability, translation, and decay. Emerging evidence indicates that m⁶A-mediated regulation is essential across multiple stages of spermatogenesis, including SSC self-renewal and differentiation, meiotic progression, maintenance of chromosomal stability, and sperm morphogenesis. Beyond its intrinsic functions in germ cells, m⁶A also contributes to the regulation of the testicular microenvironment. In sertoli cells, m⁶A is involved in maintaining blood-testis barrier integrity, RNA processing, and paracrine signaling, thereby providing structural and metabolic support for germ cell development. In Leydig cells, m⁶A regulates steroidogenesis, particularly testosterone synthesis, and participates in cellular stress responses and metabolic homeostasis. Through these mechanisms, m⁶A indirectly influences spermatogenesis by modulating the functional state of testicular somatic cells, highlighting an integrated regulatory mode that combines cell-intrinsic and microenvironment-mediated effects. Notably, distinct classes of m⁶A regulators exhibit pronounced stage-specific functions and coordinated division of labor, collectively forming a multilayered and dynamic regulatory network. Writers often display dosage- and temporal window-dependent effects; erasers contribute to stage-specific demethylation and functional compensation; while readers function through a “switch-buffer” dual-layer architecture, and RNA-binding proteins (RBPs) participate in substrate selection and post-transcriptional regulation. Importantly, emerging evidence suggests that some m⁶A-related proteins can function through noncanonical mechanisms independent of m⁶A recognition, such as intrinsic RNA-binding activity, helicase function, or ribonucleoprotein complex assembly, thereby expanding the functional landscape of the m⁶A regulatory system. Dysregulation of m⁶A machinery can lead to multiple spermatogenic defects, including impaired SSC self-renewal, meiotic arrest, abnormal chromatin remodeling, and defective sperm formation, ultimately resulting in male infertility. Despite substantial advances, several critical questions remain unresolved, including the distinction between m⁶A-dependent and -independent mechanisms, the spatiotemporal dynamics of m⁶A modifications at single-cell resolution, and the coordination and antagonism among different regulatory factors. In this review, we systematically summarize the dual regulation of spermatogenesis by germ cell-intrinsic mechanisms and the testicular microenvironment, and delineate the molecular mechanisms and stage-specific functions of the dynamic m⁶A regulatory network. We further discuss the current limitations in the field and propose feasible experimental strategies for future investigation. Collectively, this work aims to provide a comprehensive framework for understanding the epitranscriptomic regulation of spermatogenesis and to offer theoretical insights into the pathogenesis and clinical management of male infertility.

Spermatogenesis is a highly ordered and spatiotemporally regulated developmental process in the male reproductive system, during which spermatogonial stem cells (SSCs), supported by the seminiferous tubule microenvironment, sequentially undergo mitosis, meiosis, and spermiogenesis to ultimately generate structurally intact spermatozoa. This complex process is accompanied by extensive transcriptional reprogramming, chromatin remodeling, and finely tuned post-transcriptional regulation. Precise control of RNA fate is therefore essential for maintaining the continuity and fidelity of spermatogenesis, and its disruption represents a major molecular basis of male infertility. N⁶-methyladenosine (m⁶A), the most abundant internal RNA modification in eukaryotes, has emerged as a critical regulator of post-transcriptional gene expression. m⁶A methyltransferases (“writers”) catalyze the addition of a methyl group to the N⁶ position of adenosine, m⁶A demethylases (“erasers”) remove the modification, and m⁶A-binding proteins (“readers”) recognize m⁶A-modified transcripts. Through the coordinated actions of these factors, m⁶A regulates transcript fate at multiple levels, including RNA splicing, nuclear export, stability, translation, and decay. Emerging evidence indicates that m⁶A-mediated regulation is essential across multiple stages of spermatogenesis, including SSC self-renewal and differentiation, meiotic progression, maintenance of chromosomal stability, and sperm morphogenesis. Beyond its intrinsic functions in germ cells, m⁶A also contributes to the regulation of the testicular microenvironment. In sertoli cells, m⁶A is involved in maintaining blood-testis barrier integrity, RNA processing, and paracrine signaling, thereby providing structural and metabolic support for germ cell development. In Leydig cells, m⁶A regulates steroidogenesis, particularly testosterone synthesis, and participates in cellular stress responses and metabolic homeostasis. Through these mechanisms, m⁶A indirectly influences spermatogenesis by modulating the functional state of testicular somatic cells, highlighting an integrated regulatory mode that combines cell-intrinsic and microenvironment-mediated effects. Notably, distinct classes of m⁶A regulators exhibit pronounced stage-specific functions and coordinated division of labor, collectively forming a multilayered and dynamic regulatory network. Writers often display dosage- and temporal window-dependent effects; erasers contribute to stage-specific demethylation and functional compensation; while readers function through a “switch-buffer” dual-layer architecture, and RNA-binding proteins (RBPs) participate in substrate selection and post-transcriptional regulation. Importantly, emerging evidence suggests that some m⁶A-related proteins can function through noncanonical mechanisms independent of m⁶A recognition, such as intrinsic RNA-binding activity, helicase function, or ribonucleoprotein complex assembly, thereby expanding the functional landscape of the m⁶A regulatory system. Dysregulation of m⁶A machinery can lead to multiple spermatogenic defects, including impaired SSC self-renewal, meiotic arrest, abnormal chromatin remodeling, and defective sperm formation, ultimately resulting in male infertility. Despite substantial advances, several critical questions remain unresolved, including the distinction between m⁶A-dependent and -independent mechanisms, the spatiotemporal dynamics of m⁶A modifications at single-cell resolution, and the coordination and antagonism among different regulatory factors. In this review, we systematically summarize the dual regulation of spermatogenesis by germ cell-intrinsic mechanisms and the testicular microenvironment, and delineate the molecular mechanisms and stage-specific functions of the dynamic m⁶A regulatory network. We further discuss the current limitations in the field and propose feasible experimental strategies for future investigation. Collectively, this work aims to provide a comprehensive framework for understanding the epitranscriptomic regulation of spermatogenesis and to offer theoretical insights into the pathogenesis and clinical management of male infertility.

Burning mouth syndrome remains a frequent source of diagnostic delay, repeated consultations, and fragmented care because it has long been treated as a “diagnosis of exclusion.” Recent updates in orofacial pain classification and research diagnostic frameworks support a practical shift: from an exclusionary label toward a structured diagnostic algorithm and staged, phenotype-guided management. This narrative, algorithm-focused clinical review aims to summarize clinically actionable evidence and to propose a “minimum sufficient workup” that prioritizes safety, efficiency, and patient-centered communication.We first outline pragmatic diagnostic criteria and key symptom patterns, then integrate current concepts of mixed mechanisms—peripheral neuropathic features, centralociplastic amplification, and psychosocial modulators—that account for symptom fluctuation and discordance between symptom severity and objective findings. The core of this review is a one-page stepwise algorithm: (1) confirm chronicity and absence of visible mucosal disease, (2) screen for red flags requiring urgent evaluation, (3) address common local contributors (e.g., candidiasis, irritants, contact allergy, xerostomia), (4) perform a targeted systemic/medication/deficiency panel, and (5) phenotype patients to guide staged treatment choices and follow-up. Finally, we provide a practical management framework emphasizing education, trigger control, and individualized combinations of topical, systemic, and behavioral interventions with predefined reassessment intervals. Future priorities include phenotype-stratified randomized trials and implementation outcomes that quantify reductions in diagnostic delay, misdiagnosis, and unnecessary testing.

Objective: Janus kinase (JAK) inhibitors are widely used to treat rheumatoid arthritis (RA); however, comparative analyses regarding their adverse events remain limited. This study aimed to compare the effects of different JAK inhibitors (tofacitinib, baricitinib, and upadacitinib) on hematological parameters in patients with RA in a real-world setting. Methods: This retrospective analysis included 552 patients with RA treated with JAK inhibitors between August 2015 and February 2024. Hematological parameters, including absolute neutrophil count (ANC) and platelet count, were assessed at baseline and after 6 months of treatment. Statistical analysis was performed to evaluate changes over time, and logistic regression analysis identified factors associated with hematologic alterations. Results: The 552 patients were divided into three groups: tofacitinib (n=264), baricitinib (n=143), and upadacitinib (n=145). No significant differences in baseline hematological parameters were observed across the groups. After 6 months, ANC decreased in all groups without significant differences among them (p=0.465). Patients receiving baricitinib had significantly higher platelet counts than those receiving tofacitinib (Pillai’s trace value of 0.063, p<0.001) or upadacitinib (Pillai’s trace value of 0.029, p<0.001).Multivariate analysis revealed that baricitinib was significantly associated with increased platelet counts (odds ratio, 2.009; 95% confidence interval, 1.212~3.331; p=0.007). Conclusion Although all three JAK inhibitors reduced ANC, baricitinib was associated with a substantial increase in platelet counts. These findings highlight the differences in adverse effect profiles among JAK inhibitors, emphasizing the importance of tailored monitoring in RA management.

Objective: To evaluate the diagnostic performance of the “probable hepatocellular carcinoma (HCC)” category in the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) v2022 guidelines. Materials and Methods: This multicenter retrospective study included patients at risk of HCC who underwent gadoxetic acid-enhanced MRI between January 2015 and June 2018; a subgroup of these patients also underwent liver CT. Eligible patients had at least one non-cystic lesion (≥10 mm) with a reference standard. Four radiologists interpreted the images independently and the results were pooled. The performance of “definite HCC” and “probable HCC” together and “probable HCC” alone were compared between v2018 and v2022. Results: A total of 2,237 patients (1,666 men; mean age, 59 ± 11 years) with 2,445 lesions were included. In v2022, 1.5% (143/9,780) of the lesions were additionally categorized as “probable HCC” by four reviewers on MRI; among these, 104 lesions were not HCCs. Focal nodular hyperplasia (FNH) or FNH-like nodules constituted 90.4% (94/104) of the false positives. When “definite HCC” and “probable HCC” were combined, v2022 showed higher sensitivity (83.7% [5,670/6,776] vs. 83.1% [5,631/6,776]) but lower specificity (77.1% [2,316/3,004] vs. 80.6% [2,420/3,004]) than v2018 (P < 0.001). For “probable HCC” alone, v2022 showed a lower positive predictive value (PPV) than v2018 (64.1% [373/582] vs. 76.1% [334/439], P < 0.001). In v2022, lesions with non-rim arterial-phase hyperenhancement (APHE) showed a lower PPV than those without APHE (42.3% [91/215] vs. 76.8% [282/367], P < 0.001). In the CT subgroup (n = 1,590), 1.6% (99/6,360) of the lesions were reassessed as “probable HCC,” and its PPV was 83.8% (83/99) in v2022 whereas no lesions were classified as “probable HCC” under v2018. Conclusion The revised “probable HCC” category in the KLCA-NCC v2022 aligns with updates in the diagnostic flow, demonstrating acceptable performance on MRI and CT. Notably, FNH or FNH-like nodules can be misclassified as “probable HCC” when MRI is used.

Objective: To compare two breast cancer screening strategies, digital mammography (DM) plus radiologist-interpreted automated breast ultrasound (ABUS) and DM plus selective ABUS review, in which only examinations positive for DM or flagged by ABUS artificial intelligence–computer-aided diagnosis (AI-CAD) were reviewed by radiologists. Materials and Methods: This retrospective study included asymptomatic women who underwent DM and ABUS screening for breast cancer between March 2022 and March 2023. The radiologists’ interpretations of DM and ABUS without AI assistance (DM + ABUS_radiologist) were collected from the clinical radiology reports. A selective DM plus ABUS reading strategy was simulated, in which only cases interpreted as positive in the radiologist’s DM report or flagged by retrospectively applied ABUS AI-CAD were triaged for further evaluation through a full review by radiologists (DM + ABUS_AI-CAD). The cancer detection rate (CDR), sensitivity, specificity, and abnormal interpretation rate (AIR) were calculated and compared between DM + ABUS_ radiologist and DM + ABUS_AI-CAD groups using the McNemar’s test. Results: Among 2,275 women (mean age, 56.1 ± 8.6 years), 12 cancers were diagnosed. The sensitivity, CDR and AIR for DM + ABUS_radiologist was 83.3% (10/12; 95% confidence interval [CI]: 51.6–97.9), 4.4 (10/2,275; 95% CI: 2.1–8.1) per 1,000 screening examinations and 16.7% (379/2,275; 95% CI: 15.1–18.3), respectively. DM + ABUS_AI-CAD triaged 84.0% (1,910/2,275) of the examinations as negative in both DM reports and retrospectively applied ABUS AI-CAD, requiring radiologist reassessment in only 16.0% (365/2,275). This approach reduced the AIR to 7.3% (167/2,275) and improved the specificity from 83.7% (1,894/2,263) to 93.1% (2,107/2,263) (all P < 0.001), while maintaining a CDR of 4.8 per 1,000 and a sensitivity of 91.7% (11/12) (all P > 0.999), compared to the DM + ABUS-radiologist. Conclusion An AI-CAD-assisted selective ABUS reading strategy reduces unnecessary recalls and improves specificity, which may help optimize reading priorities and reduce the reading workload while maintaining cancer detection performance.

Objective: This study aimed to compare the therapeutic outcomes of no-touch (NT) radiofrequency ablation (RFA) vs. tumorpuncture microwave ablation (MWA) in the treatment of single hepatocellular carcinomas (HCCs) measuring ≤3 cm. Materials and Methods: This multicenter retrospective study included 304 patients who underwent either NT-RFA (n = 144) or MWA (n = 160) for a single HCC measuring ≤3 cm. Comparative analyses were conducted for the overall cohort, while 81 patients per group were matched using propensity score matching (PSM). The analyzed outcomes included technical success, primary technique efficacy, local tumor progression (LTP), and major complications. Cumulative LTP was estimated using Kaplan–Meier analysis and compared using the log-rank text, while the rate of ablative margin ≥5 mm and ablation time were compared using Chi-squared and Mann–Whitney U tests, respectively. Results: Technical success was achieved in 98.6% (142/144) and 100% (160/160) of in the NT-RFA and MWA patients, respectively before PSM (P = 0.224), and 98.8% (80/81) and 100% (81/81) after PSM (P = 1.000). The primary technique efficacies were 98.6% (142/144) and 100% (160/160) before PSM (P = 0.224), and 97.5 % (79/81) and 100% (81/81) after PSM (P = 0.497), respectively. The 1-, 2-, and 3-year cumulative LTP rates were 1.4%, 1.4%, and 2.3%, respectively, for NTRFA and 5.1%, 8.6%, and 8.6%, respectively, for MWA before PSM (P = 0.013). After PSM, the corresponding rates were 0%, 0%, and 0% for NT-RFA, and 7.6%, 10.4%, and 10.4% for MWA (P = 0.006). Major complications were not observed. NT-RFA achieved a higher proportion, with an ablative margin ≥5 mm (88.7% [126/142] vs. 71.9% [115/160]; P < 0.001), but required longer ablation times (median, 10.0 vs. 6.0 min; P < 0.001). Conclusion NT-RFA showed superior local tumor control compared to MWA, despite greater procedural complexity and longer ablation times.

Zelkova serrata (Thunb.) Makino is a deciduous tree commonly distributed in East Asia. Several investigations have documented the biological activity of extracts of this species, igniting increased interest in its therapeutic potential. However, the phytochemical constituents accountable for these activities remain largely unexplored. In this study, we focused on the antioxidant potential of the leaves and twigs, utilizing bioactivityguided fractionation combined with LC-QTOF-MS online DPPH screening to systematically identify the active compounds. This approach led to the isolation of eight compounds, three of which (compounds 1, 3, and 7) have not previously been documented in the genus Zelkova. Among the isolates, 4 emerged as the most potent antioxidant, exhibiting significant radical scavenging activity in both DPPH (IC 50 = 13.67 ± 1.21 μM) and ABTS (IC50 = 2.69 ± 0.48 μM) assays, exceeding ascorbic acid (IC 50 = 61.51 ± 10.22 μM) and trolox (IC50 = 8.22 ± 2.16 μM), respectively. Our findings not only enrich the phytochemical profile of Z. serrata but also highlight the effectiveness of LC-MS-DPPH as an effective approach for rapid antioxidant discovery.

Purpose: Due to its rarity, treatment guidelines for appendiceal cancer have traditionally followed those established for colorectal cancer, despite showing distinct histologic and clinical features. This study aimed to compare the clinicopathologic characteristics and long-term oncologic outcomes of appendiceal cancer with those of right-sided colon cancers. Methods: We retrospectively reviewed the records of patients with stage I–III appendiceal, cecal, or ascending colon cancer who underwent curative resection between 2010 and 2020 at our center. A 1:3:3 exact matching for age, sex, TNM stage, and adjuvant chemotherapy was performed. Survival outcomes were analyzed using the Kaplan-Meier and Cox regression methods. Results: Overall, 245 patients with appendiceal cancer (n = 35), ascending colon cancer (n = 105), and cecal cancer (n = 105) were analyzed. Appendiceal cancer exhibited a higher proportion of T4 tumors and fewer harvested lymph nodes compared with ascending or cecal cancers. The mean follow-up duration was 9.5 years. The 5- and 10-year overall survival rates were lower in appendiceal cancer (66.2% and 52.9%) than in ascending (91.2% and 78.4%) or cecal cancer (88.5% and 78.3%). Similarly, the 10-year disease-free survival rate was lower in appendiceal cancer (59.2%) compared with ascending (83.1%) and cecal cancers (78.4%). Cox regression analysis identified age (≥65 years), perforation, nodal metastasis, and lymphovascular invasion as independent predictors of poor prognosis. Conclusion Appendiceal cancer exhibited significantly worse long-term survival compared to cecal or ascending colon cancer. Tumor perforation, nodal metastasis, and lymphovascular invasion were adverse prognostic factors for overall and disease-free survival.

Purpose: While MRI-based tumor regression grade (mrTRG) has shown promise in evaluating pathologic response to concurrent chemoradiotherapy (CCRT) in rectal cancer, its ability to predict pathologic complete response remains limited.This study aimed to enhance mrTRG’s diagnostic performance in predicting ypT0–1N0 status, a key factor in considering non-radical management after CCRT for locally advanced rectal cancer (LARC). Methods: This retrospective study included 430 patients with LARC who underwent radical resection following CCRT at a single referral hospital between April 2018 and September 2024. Multivariable logistic regression was used to identify predictive factors associated with achieving ypT0–1N0 status. The diagnostic performances of mrTRG1–2 alone and in combination with other factors were assessed by comparing sensitivity, specificity, positive-predictive value (PPV), negative-predictive value, and area under the curve (AUC). Results: Ninety-three patients (21.6%) achieved ypT0–1N0. In the multivariable analysis, fungating type, cT1–2, and mrTRG1–2 were independent predictors for ypT0–1N0. Integrating mrTRG with gross tumor type yielded the highest AUC of 0.689 among the combined models. For predicting ypT0–1N0, the combination of mrTRG and gross tumor type improved PPV (79.2% vs. 41.5% for mrTRG alone) while also demonstrating enhanced sensitivity compared with ycT0–1N0, the conventional MRI-based predictor (40.9% vs. 22.6%). Conclusion This study demonstrated that combining mrTRG and gross tumor type improved the PPV of mrTRG in predicting ypT0–1N0 after CCRT in LARC. Further studies are warranted to validate the role of gross tumor type in refining predictive systems for selecting candidates for non-radical treatment.