This study focuses on the core pathology of sinew wei （痿）， which is mainly characterized by the fai-lure of qi and blood to nourish the sinews. A mechanical-biological response framework is constructed with mitochondria as a key component， explaining the modern interpretation of the disease location of sinew transmitting to qi and blood pathology. Mechanical loading， as a physical stress stimulus applied to the body， manifests primarily as passive loading formed by external forces such as massage， and active loading resulting from voluntary muscle contractions， such as dao yin （导引）. Mechanical loading can regulate mitochondrial function through two pathways， mechanical signal transduction and metabolic demand-driven regulation. Skeletal muscle mitochondrial dysfunction is regarded as the core microscopic basis of qi imbalance in sinew wei， highlighting the intrinsic connection between qi and mitochondrial energy metabolism， as well as between blood and microcirculatory efficiency. Accordingly， distinct regulatory patterns of mechanical loading are identified. Wei associated with qi stagnation may correspond to mitochondrial network fragmentation and can be treated by regulating qi through passive loading， such as tuina， to restore mitochondrial dynamics. In contrast， wei caused by qi deficiency is attributed to insufficient mitochondrial biogenesis and may be treated by tonifying qi through active loading， such as dao yin， to promote mitochondrial biogenesis. This framework reveals the biological differences in mitochondrial regulation induced by distinct mechanical loading modalities and provides a microscopic mechanism-based explanation for the principle of "treating the same disease with different methods" in sinew wei.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Purpose: Persistent hypercalcemia after parathyroidectomy (PTx) remains a significant concern in patients with tertiary hyperparathyroidism (THPT) following kidney transplant (KT). Complete resection of hyperfunctioning glands is challenging due to ectopic or intrathyroidal glands. This study evaluated whether intraoperative parathyroid hormone (ioPTH) monitoring during PTx in KT patients with THPT reduces the surgical failure rate. Methods: We retrospectively analyzed 111 patients with THPT who underwent PTx at a single tertiary center. Patients were divided into 2 groups: those without ioPTH monitoring (n=98) and those with ioPTH monitoring (n=13). Surgical procedures included less than subtotal, subtotal, or total PTx with autotransplantation. Surgical failure was defined as persistent hypercalcemia (serum calcium ≥10.3 mg/dL and intact parathyroid hormone [PTH] >65 pg/mL) on postoperative day 1 (POD1) or at ≥6 months postoperatively. Results: The ioPTH group demonstrated a significantly lower mean PTH level on POD1 (21±15.3 pg/mL vs. 39±39 pg/mL; P=0.006). Although not statistically significant, the ioPTH group showed a higher biochemical cure rate at 3 months (53.8% vs. 30.6%) and no cases of persistent hyperparathyroidism, compared to 15.3% in the non-ioPTH group.Despite adequate intraoperative PTH reduction, some patients in both groups exhibited isolated PTH elevation without hypercalcemia. Conclusion Although ioPTH monitoring did not significantly reduce the surgical failure rate in PTx for THPT, the use of ioPTH may meaningfully improve surgical completeness and reduce the risk of persistent or recurrent hyperparathyroidism, suggesting its substantial potential value as an intraoperative.

Purpose: Although gastric cancer (GC) exhibits significant genomic heterogeneity, the clinical implications of its immune microenvironment remain poorly understood. Materials and Methods: We retrospectively evaluated patients with GC who underwent gastrectomies between 2011 and 2014. The tumors were analyzed for Epstein–Barr virus (EBV), microsatellite instability-high (MSI-H), tumor-infiltrating lymphocytes (CD3), tumor-associated macrophages (CD68 and CD163), and programmed death-ligand 1 (PD-L1) expression. Tumors were classified using the modified The Cancer Genome Atlas scheme, and their clinical characteristics were compared. Results: A total of 567 patients were classified into EBV (6%), MSI-H (10%), chromosomal instability-like (36%), and genomically stable-like (48%) subtypes. EBV tumors exhibited the highest PD-L1 expression (85%) and immune infiltration by CD3+ T cells (86%), CD68+ macrophages (58%), and CD163+ macrophages (40%). High CD68+ macrophage tumors were associated with advanced stages and worse 5-year disease-free survival (83% vs. 95%; P<0.001);however, this association was not independently significant after adjusting for the tumor-nodemetastasis stage. PD-L1 expression did not significantly affect the survival outcomes. Conclusions GC subtypes have distinct immune microenvironments that influence prognosis. Our findings highlight the prognostic and therapeutic potential of immune profiling in GC.

Purpose: Esophagojejunal anastomotic leakage (EJAL) represents a severe postoperative complication following total or proximal gastrectomy. Treatment strategies include conservative management, endoscopic interventions, and surgery; however, comparative data remain limited. This study aimed to compare clinical outcomes of different strategies to identify the optimal approach based on anastomotic defect size. Materials and Methods: This retrospective study reviewed 100 patients diagnosed with EJAL between January 2015 and October 2024. Patients were categorized into four groups:conservative management, endoscopic vacuum-assisted closure (E-VAC), other endoscopic treatments, and surgery. The primary outcomes were leakage duration and length of hospital stay after EJAL diagnosis, whereas the secondary outcome was time to C-reactive protein normalization. Subgroup analyses were performed according to defect size. Results: Among the 100 patients, 76 were male and 24 were female, with a mean age of 65.7 years. Conservative treatment was the most common modality (53%), followed by other endoscopic treatments (19%), E-VAC (14%), and surgery (14%). In patients with a defect size <1 cm, conservative treatment was associated with significantly shorter leakage duration (P=0.035) and earlier resumption of diet (P=0.029) compared with endoscopic treatment.Among those with defects ≥2 cm, E-VAC demonstrated the most favorable median outcomes across all variables; however, statistical significance was not achieved because of the small sample size. Conclusions Conservative treatment appears to be the most effective treatment strategy for EJAL with anastomotic defects <1 cm. For larger defects (≥2 cm), E-VAC may offer clinical benefit, although further studies are needed to confirm its efficacy. These findings highlight the importance of individualized treatment selection based on defect size.

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.

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.

Background: Psoriasis is a chronic inflammatory skin disorder typified by well-demarcated erythematous plaques with scales. While considered an immune-driven condition, its underlying molecular triggers remain insufficiently defined. Cold-inducible RNA-binding protein (CIRP), a stress-response protein, has recently been recognized as a damage-associated molecular pattern that can stimulate immune responses. Objective: This study aimed to explore the potential association between circulating CIRP levels and the clinical as well as histological characteristics of psoriasis. Methods: Serum CIRP concentrations were analyzed in 67 individuals diagnosed with psoriasis and 20 healthy controls. Relationships between CIRP expression and various clinical and histological indices were also examined. Results: Patients with psoriasis exhibited significantly elevated serum CIRP levels compared to healthy individuals. Although correlations were observed between CIRP and certain clinical and histological indicators, CIRP levels did not significantly differ based on disease severity (Psoriasis Area and Severity Index score), joint involvement, or nail changes. Conclusion Our findings support the notion that CIRP may be involved in the immunopathogenesis of psoriasis and could be considered a prospective target for therapeutic modulation.