Atrial fibrillation (AF) is a frequent arrhythmia in sepsis patients and is traditionally regarded as a harmful epiphenomenon requiring immediate correction. Its abrupt onset and association with adverse outcomes have driven clinicians to pursue aggressive rhythm or rate control strategies, which are often extrapolated from cardiology rather than sepsis-specific evidence. However, emerging data challenge this reflexive approach. Studies with ultrashort-acting beta-blockers, such as esmolol and landiolol, have shown that hemodynamic stabilization may occur even in the absence of sinus rhythm restoration. This raises a provocative question: could AF during sepsis represent not a pathological disturbance but rather a transient and potentially tolerable manifestation of sepsis-related cardiovascular stress? We propose the concept of “permissive AF,” shifting the focus from rhythm restoration to hemodynamic optimization and organ perfusion. Thus, AF is not framed as a physiological adaptation per se but as a maladaptive manifestation of sepsis-related cardiac injury that may be clinically tolerated, paralleling permissive strategies in critical care, such as permissive hypercapnia or restrictive transfusion thresholds. This does not imply therapeutic inaction; rather, it is a goal-directed approach that tolerates arrhythmia when adequate rate control and perfusion are achieved. This paradigm challenges established clinical instincts and underscores the need for individualized management. Recognizing AF as a potential adaptive rhythm reframes research priorities: identifying biomarkers of atrial inflammation, stratifying patients according to hemodynamic impact, and testing permissive versus corrective strategies in prospective trials. The permissive AF strategy proposed herein is expected to foster patient-centered care and reduce iatrogenic harm in the complex interplay between sepsis and the heart.

Clinical dilemma of atrial fibrillation during sepsis. Electrical cardioversion is depicted with traditional defibrillator pads, symbolizing rhythm-focused intervention (left). Pharmacologic rate control is represented by beta-blockers and a perfused heart, highlighting a patient-centered approach on the basis of hemodynamic stability (right).

The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing continuously, posing a substantial threat to public health. This study examines the critical role of imbalanced interactions within the gut‒liver-mitochondrial axis in MASLD pathogenesis. Dysregulation of mitochondrial homeostasis, including metabolic disturbances, impaired quality control, and disrupted interorganelle interactions, significantly contributes to MASLD progression. Through the gut‒liver axis, the gut microbiota establishes a bidirectional regulatory network with mitochondria. Dysbiosis disrupts mitochondrial homeostasis via multiple pathways, while mitochondrial dysfunction aggravates imbalances in the gut microbiota, creating a vicious cycle. Therefore, in this study, the molecular basis of mitochondrial abnormalities was investigated, and the mechanisms of reciprocal regulation were clarified. Additionally, targeted intervention strategies, including the modulation of mitochondrial homeostasis and the regulation of the gut microbiota, are explored to provide novel therapeutic perspectives for MASLD.

Quantification of immunity is a challenge in clinical practice due to the complexity and heterogeneity of immune cells. This study aimed to establish comprehensive reference ranges for immune indicators and characterize immune heterogeneity in healthy adults.

A total of 115 healthy adults aged 18–65 years were enrolled. Sixty immune indicators encompassing natural immunity (NK cells, monocytes, dendritic cells, myeloid-derived suppressor cells), cellular immunity (T cells, regulatory T cells, T follicular helper cells, T helper cells), and humoral immunity (B cells), along with nutritional and metabolic indicators, were simultaneously detected. Flow cytometry was used to measure the number, phenotype, and functional subsets of immune cells. Unsupervised k-means clustering was performed to identify immune subtypes. RNA-sequencing was conducted on representative individuals from each cluster for transcriptomic validation.

The reference ranges for 60 immune indicators were established, with over half (38/60) exhibiting coefficient of variation > 30%, indicating substantial heterogeneity. Gender differences were minimal, whereas age-related changes were pronounced in adaptive immune cells. Specifically, human leukocyte antigen DR-positive (HLA-DR⁺) T cells (%) increased from 20.76% ± 7.75% (18–30 years) to 30.06% ± 10.82% (51–65 years, P = 0.001), while CD45RA⁺ regulatory T (Treg) cells (%) and naive CD8⁺ T cells (%) decreased progressively with age (P < 0.001). Correlation analysis between immune cells and routine laboratory indicators revealed that nutritional indicators like albumin (ALB) were positively correlated with the number of immune cells such as CD8⁺ T cells, while lipid metabolism indicators like low-density lipoprotein (LDL) were negatively correlated with T helper cell differentiation (P < 0.01). Clustering analysis identified three distinct immune subtypes: “potential type” (26.1%, n = 30) characterized by high naive T cells (44.91% ± 9.88% CD4⁺ T cells, 33.86% ± 13.82% CD8⁺ T cells) and CD1c-positive myeloid dendritic cells (CD1c⁺ mDCs) (45.17% ± 11.58%); “effector NK type” (34.8%, n = 45) with elevated NK cell count (704.22 ± 280.79 cells/μL) and cytotoxic function (93.16% ± 2.38% perforin⁺ NK cells); and “effector T type” (39.1%, n = 40) distinguished by increased HLA-DR⁺ T cells (19.48% ± 7.1% CD4⁺ T cells, 45.11% ± 10.92% CD8⁺ T cells) and effector memory (EM) CD4⁺ T cells (37.85% ± 11.01%). A further RNA-sequencing analysis confirmed the transcriptomic characteristics of different immune subtypes, which was in accordance with phenotype analysis. Specifically, adults in the potential type had strong adaptive immunity; those in the effector NK type showed upregulated NK cell-mediated cytotoxicity; those in the effector T type exhibited enhanced T-helper 1 immune responses.

This study provides a systematic framework for immunity quantification by establishing reference ranges and classifying healthy adults into three immune subtypes with distinct metabolic and transcriptomic features. These findings could enhance understanding of immune heterogeneity in healthy individuals and guide personalized immune monitoring and intervention strategies in clinical practice.

Hypertrophic cardiomyopathy (HCM) and ischemic cardiomyopathy (ICM) are the most common main etiologies of heart failure (HF), which is also a leading cause of mortality and morbidity; however, the common mechanisms triggering the gradual progression and evolution of HF have not yet been fully elucidated. Hence, the purpose of this study focuses on the communal biological mechanisms involved, screening and functional validation of common key genes.

The gene expression profiles of HCMs (GSE36961, GSE160997) and ICMs (GSE5406, GSE26887) were downloaded from the Gene Expression Omnibus (GEO) database. After the common genes (CGs) were identified based on the intersection of the differentially expressed genes (DEGs) from the GSE36961 and GSE5406 datasets, pathway enrichment, functional annotation, protein‒protein interaction (PPI) network, hub gene identification, transcription factor (TF)-mRNA regulatory network and diagnostic efficiency evaluation were performed. In addition, the hub genes were verified with the GSE160977 and GSE26887 datasets. These findings ultimately validated the functional role of Bcl6 in both cellular and animal experiments.

In total, 88 CGs (54 downregulated genes and 34 upregulated genes) were screened for subsequent analyses. Functional annotation and pathway enrichment revealed the important role of angiogenesis in these two diseases. Seven important hub genes were identified, including MYC, STAT3, CEBPB, CEBPD, CDKN1A, BCL6 and MAP2K1. The TF-mRNA network revealed that BCL6, STAT3, MYC and CDKN1A were closely related and might coordinately participate in common biological pathogenesis. Receiver operating characteristic (ROC) curve analysis revealed that the hub genes had great value for clinical diagnostic efficiency. The ROC curve prediction revealed that the optimal indicator in HCM and ICM is the Bcl6 protein. Overexpression of Bcl6 ameliorates cardiac phenotypes in mouse models of both HCM and ICM.

Our research revealed the common potential pathogenesis mechanism of HCM and ICM. The identification of these hub genes might provide novel directions for further treatment research, clinical diagnosis and treatment.

Vascular aging is a significant factor in cardiovascular and cerebrovascular diseases and serves as a predictor of all-cause mortality. Although disturbances in lipid metabolism are known risk factors, their links with standardized stages of vascular aging have not been thoroughly assessed in the Chinese population. This multicenter study analyzed the distribution of vascular aging stages in the China Standardized Vascular Aging Management Centers (VMCs). It investigated the relationships between lipid–adiposity–related indices and the progression of vascular aging.

A total of 668 participants who underwent examinations at multiple VMCs between June 2023 and February 2025 were included. Baseline data were collected from standardized questionnaires, anthropometric measurements, and laboratory tests. The participants were classified into stage 1 (normal vessels), stage 2 (vascular injury), and stage 3 (vascular aging–related diseases). Multiple linear and logistic regression models were used to assess associations between lipid–adiposity–related indices and brachial-ankle pulse wave velocity (baPWV) or vascular aging stages. Restricted cubic spline analyses were used to examine potential nonlinear relationships.

After controlling for demographic factors, lifestyle behaviors, comorbidities, and medication use, most lipid–adiposity–related indices showed significant positive associations with baPWV. The bilateral baPWV measurements exhibited high consistency. According to the multivariable models, waist circumference (WC), A Body Shape Index (ABSI), waist-to-hip ratio (WHR), waist-height ratio (WHtR), triglyceride (TG), atherogenic index of plasma (AIP), and lipid accumulation product (LAP) were significantly linked to vascular aging stages, with several anthropometric indices (WC, ABSI, WHR, WHtR) increasing progressively across stages. No notable nonlinear relationships were observed.

Standardized lipid–adiposity–related indices, especially WC, ABSI, WHR, and WHtR, were independently linked to baPWV and vascular aging stages.

This study aimed to investigate pregnancy outcomes after conservative treatment for severe postpartum hemorrhage (PPH) following cesarean delivery (CD).

A total of 9,366 women who underwent CD for two consecutive pregnancies were included. Bakri balloon tamponade was employed in 87 women, and compression sutures were used in 87 women to control PPH during the first CD. The subsequent pregnancy outcomes and operative findings during the second CD were compared among the groups.

The preterm delivery rate was 3.2% in the control group, 12.6% in the Bakri group, and 11.5% in the compression suture group (P < 0.001). The rates of placenta accreta (1.4% vs. 1.3% vs. 5.3%, P = 0.017), PPH (0.9% vs. 3.9% vs. 8.0%, P < 0.001), and pelvic adhesions (5.2% vs. 6.5% vs. 13.3%, P = 0.004) were significantly greater in the compression suture group. After adjustment, conservative treatment increased the rate of preterm birth in subsequent pregnancies threefold. A compression suture increased the risk of placenta accreta by four fold and the incidence of pelvic adhesions by more than two fold in subsequent CD.

Conservative treatment for PPH following CD is associated with an increased risk of subsequent preterm birth. Women receiving compression sutures have an increased risk of placenta accreta and pelvic adhesions in subsequent pregnancies.

Early prediction of the severity of acute pancreatitis (AP) is crucial for clinical decision-making and for improving patient outcomes. In this study, readily available laboratory data and Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to select key variables and construct a nomogram for accurate severity prediction in AP patients.

We retrospectively analyzed the clinical data of 965 adult AP patients hospitalized at a hospital between January 2017 and December 2019. LASSO regression was used to identify significant predictors of severe acute pancreatitis (SAP), and a nomogram prediction model was constructed. The performance of the nomogram was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, the calibration curve, and the decision curve analysis (DCA).

Among the 965 patients, the incidence of SAP was 15.96% (n = 154). Eight independent predictors were identified: C-reactive protein, lactate dehydrogenase, hematocrit, monocyte percentage, prothrombin time, D-dimer, glucose, and total cholesterol. These predictive factors were incorporated into a nomogram model, which demonstrated favorable discriminative ability, with AUC values of 0.809 in the training cohort and 0.768 in the validation cohort. The clinical utility of the model was further supported by satisfactory calibration and positive net benefits of DCA.

The proposed nomogram was highly discriminative in predicting AP severity, indicating its potential clinical value for risk stratification.

Platelet antibodies are associated with adverse pregnancy outcomes, such as miscarriage and fetal/neonatal alloimmune thrombocytopenia (FNAIT). However, data on their prevalence and risk factors in the southern Chinese population remain limited. This study aimed to investigate the prevalence of platelet antibodies and their risk factors in pregnant women from southern China, with a particular focus on their association with thyroid diseases.

Blood samples from 5,037 pregnant women presenting for delivery between June 30, 2022, and April 7, 2024, were screened for platelet antibodies via the solid-phase agglutination test. Participants were categorized as platelet antibody positive or negative based on the test results. Clinical data were compared between the two groups. Binary logistic regression analysis was performed to identify independent risk factors for platelet antibody positivity.

The overall platelet antibody positivity rate was 7.68%. The positivity increased significantly with both a greater number of pregnancies and a history of miscarriage. Notably, thyroid diseases were strongly associated with platelet antibodies: women with thyroid diseases had a significantly higher positivity rate of 11.55%. Specifically, Hashimoto’s thyroiditis (HT) and thyroid nodules were identified as significant independent risk factors in the binary logistic regression analysis. Other significant independent risk factors included a history of blood transfusion, three or more pregnancies, three or more miscarriages, and thalassemia.

This study provides novel evidence of a significant association between maternal thyroid disorders (particularly HT and thyroid nodules) and a higher prevalence of platelet antibodies during pregnancy. These findings highlight the importance of considering thyroid status in antenatal care and suggest a potential benefit of proactive platelet antibody screening, especially in women with thyroid diseases, to help mitigate associated risks such as miscarriage and FNAIT.

Trefoil factor 3 (TFF3), a secreted protein involved in mucosal protection and tumor progression, has an incompletely defined role in breast cancer (BRCA). This study aimed to comprehensively evaluate TFF3 expression patterns, clinical relevance, and prognostic significance in BRCA.

Data from the TCGA, GTEx, TNMplot, and TISCH2 databases were integrated to analyze TFF3 expression and clinical significance. Protein expression in clinical samples was validated via immunohistochemistry (IHC), and survival analysis, immune infiltration assessment, and functional enrichment analyses were performed to explore the biological role of TFF3.

TFF3 was significantly upregulated in BRCA tumor tissues compared with normal tissues (P < 0.001) and was expressed predominantly in malignant cells and tumor-associated macrophages. High TFF3 expression correlated strongly with hormone receptor (estrogen receptor/progesterone receptor) positivity, luminal A/B subtypes, and early-stage disease (P < 0.01) and showed excellent diagnostic performance for distinguishing basal-like from non-basal-like BRCA (AUC = 0.95). TFF3 was an independent protective factor: high expression was associated with improved overall survival (HR = 0.75, P = 0.02) and disease-free survival (P < 0.001), especially in patients receiving hormone therapy (HR = 0.89, P = 0.0002) or chemotherapy (HR = 0.89, P = 0.0002). TFF3 exhibited immunomodulatory properties, correlated positively with M2 macrophages and negatively with cytotoxic immune cells (CD8⁺ T cells, NK cells) and checkpoint molecules (PD-1, CTLA-4) (P < 0.01). Functional analyses linked TFF3 to estrogen response pathways and cell cycle regulation. IHC validation confirmed TFF3 overexpression in 78.1% of tumors versus 23.9% of normal tissues (P < 0.001), with the lowest expression in the basal-like subtype (8.33% vs. 59.2%, P = 0.0007).

TFF3 is a robust diagnostic biomarker for BRCA molecular subtyping, an independent prognostic factor, and a potential immunomodulator. These findings highlight its clinical utility for patient stratification and potential as a therapeutic target, particularly in hormone receptor-positive BRCA.

Activating transcription factor 6 (ATF6) is a part of the unfolded protein response (UPR) system, which plays an important role in regulating endoplasmic reticulum stress. The overexpression of ATF6 has been reported in various malignancies; however, its expression and functional significance in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) are poorly understood.

Bone marrow samples from 69 pediatric patients with ALL (48 newly diagnosed, 21 relapsed) and peripheral blood/bone marrow samples from 29 nonleukemic healthy children (controls) were collected. To investigate the effect of ATF6 inhibition on the viability of BCP-ALL derived cell lines, NALM-6 and SUP-B15 cells were treated with the ATF6 inhibitor Ceapin-A7 both alone and in combination with doxorubicin. Apoptosis was quantitatively assessed using flow cytometry. The expression levels of ATF6, BCL-2 family members, and ATF6 target genes were determined by qRT-PCR, and the protein levels of ATF6, caspase-3, PARP, cell cycle regulators by Western blot analysis.

Our results revealed that the ATF6 expression was higher in pediatric patients with relapsed ALL than in newly diagnosed patients. Furthermore, inhibition of ATF6 with Ceapin-A7 enhanced doxorubicin-induced apoptosis in the BCP-ALL cell lines NALM-6 and SUP-B15. Upon inhibition of ATF6, both BCP-ALL cell lines were arrested at the G1 phase of the cell cycle. Combined treatment altered the expression of apoptosis-related and cell cycle regulatory genes and proteins, and ATF6 target genes were upregulated by Ceapin-A7 alone but attenuated in the combined treatment group.

ATF6 inhibition combined with doxorubicin represents a promising therapeutic strategy for enhancing apoptosis in BCP-ALL cells.

Identifying novel molecular drivers is crucial to improving therapeutic strategies for hepatocellular carcinoma (HCC). This study aimed to investigate the clinical significance and biological function of UDP-glucuronate decarboxylase 1 (UXS1) in HCC.

UXS1 expression and its prognostic value were analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) database. In vitro, UXS1 was silenced in Huh-7 and HCCLM3 cell lines via siRNA. Malignant phenotypes were evaluated using CCK-8, Transwell, and wound healing assays. Transcriptome sequencing (RNA-seq) was performed to identify downstream mechanisms. Additionally, oxidative stress markers (catalase, superoxide dismutase, and glutathione) and key ferroptosis regulators (GPX4, SLC7A11) were assessed. Notably, rescue experiments using the ferroptosis inhibitor Ferrostatin-1 were conducted to validate the mechanism.

UXS1 mRNA expression was significantly upregulated in HCC tissues, and high expression correlated with poor overall and progression-free survival. Functionally, UXS1 knockdown significantly inhibited HCC cell proliferation, migration, and invasion. Transcriptome analysis of 425 differentially expressed genes (DEGs) highlighted the enrichment of reactive oxygen species (ROS) and ferroptosis-related pathways. Mechanistically, UXS1 silencing disrupted ROS homeostasis and downregulated the anti-ferroptotic proteins GPX4 and SLC7A11. Significantly, treatment with Ferrostatin-1 effectively reversed the tumor-suppressive effects of UXS1 knockdown.

High expression of UXS1 serves as a prognostic biomarker for HCC. UXS1 knockdown suppresses HCC malignant progression, at least partially, by inducing ferroptosis via the SLC7A11/GPX4 axis. These findings suggest UXS1 is a potential therapeutic target and a novel ferroptosis checkpoint in HCC.

The diagnosis and treatment of hepatocellular carcinoma (HCC) remain unsatisfactory, underscoring the urgent need to explore new regulatory factors. This study aimed to uncover the regulatory role of mitochondrial ribosomal protein L42 (MRPL42) in HCC development and assess its clinical potential as a therapeutic target and prognostic biomarker.

MRPL42 expression in HCC was analyzed in datasets obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. MRPL42 expression was detected via reverse transcription quantitative polymerase chain reaction and immunohistochemistry, and its diagnostic and prognostic abilities were assessed via receiver operating characteristic (ROC) curves and Kaplan–Meier curves. Cell proliferation was assessed via the Cell Counting Kit-8 assay, migration via the wound healing assay, and invasion via Transwell experiments. The molecular mechanisms underlying MRPL42 knockdown-mediated suppression of HCC progression were analyzed via transcriptome sequencing. Western blot analysis was used to measure protein levels. The ATP content and mitochondrial respiratory chain complex I activity were determined via commercial reagent kits.

MRPL42 overexpression predicted HCC occurrence and poor prognosis. MRPL42 knockdown suppressed the malignant functions of HCC. Transcriptomic analysis revealed that differentially expressed genes after MRPL42 knockdown were closely linked to oxidative phosphorylation (OXPHOS). MRPL42 knockdown inhibited the protein expression of the mitochondrial activity markers PGC-1α and MT-ND1 and reduced ATP content and mitochondrial respiratory chain complex I activity, indicating that MRPL42 deficiency impaired mitochondrial OXPHOS. Furthermore, MRPL42 knockdown suppressed the malignant functions of HCC cells by regulating OXPHOS.

MRPL42 is overexpressed in HCC and is a potential biomarker for HCC diagnosis and prognosis. In regulating OXPHOS, MRPL42 knockdown suppressed HCC malignant function, highlighting its potential as a therapeutic target.

Physical symptoms severely impair quality of life (QoL) in patients with gastrointestinal cancers (GICs). Although illness acceptance is recognized as a key mediator, the distinct rols of its two dimensions—active acceptance and negative acceptance—remain underexplored in the symptom-QoL pathway. This study aimed to explore their parallel mediating roles.

In this cross-sectional study, 301 inpatients with GICs completed the MD Anderson Symptom Inventory (MDASI), the 12-item Short Form Health Survey (SF-12), the Illness Cognition Questionnaire-Acceptance subscale (ICQ-A, measuring active acceptance), and the Medical Coping Modes Questionnaire (MCMQ, measuring negative acceptance). Parallel mediation analysis was performed using PROCESS Model 4 with bootstrap resampling (5,000 iterations).

Symptom severity was negatively correlated with QoL (r = −0.69, P < 0.01) and active acceptance (r = −0.47, P < 0.01), and positively correlated with negative acceptance (r = 0.56, P < 0.01). Active acceptance was positively (r = 0.60) and negative acceptance negatively (r = −0.60) correlated with QoL (both P < 0.01). Mediation analysis revealed two significant indirect pathways: symptoms → reduced active acceptance → lower QoL, accounting for 23.92% of total effect (95% bootstrap CI [−0.068, −0.033]), and symptoms → increased negative acceptance → lower QoL, accounting for 25.36% of total effect (95% bootstrap CI [−0.074, −0.035]). Neither confidence interval contained zero.

Both active acceptance and negative acceptance independently mediate the relationship between physical symptoms and QoL in patients with GICs. Active acceptance buffers the impact of symptoms, whereas negative acceptance exacerbates it. These findings support integrating psychological interventions that foster active acceptance and mitigate negative acceptance as a core component of symptom management to optimize QoL in this population.

This study investigated the role and underlying mechanism of large tumor suppressor 1/2 (LATS1/2), a core kinase in the Hippo pathway, in inhibiting osteoclastic differentiation and ameliorating ovariectomy (OVX)-induced osteoporosis in rats through the RANKL-dependent Hippo–YAP/TAZ signaling pathway both in vivo and in vitro.

Under stimulation by receptor activator of nuclear factor-κB ligand (RANKL), small interfering RNA (siRNA) was used to suppress the expression of LATS1/2 and YAP. The levels of osteoclast-related genes and proteins, as well as YAP pathway proteins, were evaluated in RAW264.7 cells and bone marrow-derived macrophages (BMMs) via quantitative reverse transcription polymerase chain reaction and Western blot analysis. Cell viability and osteoclast formation potential were measured via the Cell Counting Kit-8 assay and tartrate-resistant acid phosphatase (TRAP) staining, respectively. Osteoclasts and filamentous actin were stained with TRAP and phalloidin to characterize cell morphology. Furthermore, to research the role of the Hippo/YAP pathway, we used siRNA to knock down LATS1/2 and examined its effect on RANKL-mediated osteoclast differentiation. In addition, we constructed an OVX-induced osteoporosis model in 8-week-old female Sprague‒Dawley rats, treated them with a LATS1/2 inhibitor for 4 weeks at 12 weeks after surgery, and evaluated the remission of osteoporosis by micro-CT and histological methods with a LATS1/2 inhibitor.

After LATS1/2 was silenced or inhibited in BMMs and RAW264.7 cells, YAP was significantly upregulated and YAP phosphorylation and osteoclast function were inhibited. By interfering with YAP expression, the Hippo/YAP pathway inhibited osteoclast differentiation in BMMs. In vivo, injection of LATS1/2 inhibitor alleviated osteoporosis in ovariectomized rats.

Our findings indicate that the inhibition of LATS1/2 considerably suppresses osteoclast differentiation and alleviates OVX-induced osteoporosis in rats. Additionally, our results show that LATS1/2 inhibitors are important for the differentiation of osteoclasts and highlight the possible therapeutic value of LATS1/2 inhibitors.

Intervertebral disc degeneration (IDD) is the main cause of low back pain, which is closely related to an imbalance in extracellular matrix decomposition–anabolism mediated by immune inflammation. Duhuo Jisheng decoction (DHJSD) is effective in treating IDD, but its specific mechanism of action remains unclear and warrants further study. This study aimed to investigate the role of DHJSD in IDD treatment and its underlying mechanisms of action, providing potential therapeutic targets for IDD.

High-performance liquid chromatography‒mass spectrometry (HPLC‒MS/MS) was employed to characterize the chemical composition of DHJSD. A Cell Counting Kit-8 (CCK-8) was used to detect the effects of DHJSD on the viability of pressure-treated nucleus pulposus (NP) cells. NP cells were randomly divided into three groups: control, pressure, and DHJSD groups. Western blotting was used to detect the expression of NLRP3, ASC, caspase-1, IL-1β, collagen II, aggrecan, Sox-9, MMP-3, MMP-13, and Adamts-4 in the aforementioned three groups of cells. An immunofluorescence assay was used to detect NLRP3 expression. Additional groups included the DHJSD + dimethyl sulfoxide (DMSO) and DHJSD + cyclosporine A groups. The expression of mitophagy-related factors, the NLRP3 inflammasome, and subsequent inflammatory reactions were detected by Western blotting and immunofluorescence. Network pharmacology and molecular docking were used to explore the key components and key genes of DHJSD involved in treating IDD. Finally, we verified the bioinformatics results using a rat tail acupuncture model of IDD.

DHJSD-containing serum improved NP cell viability; the optimal intervention concentration was 20% by volume, and the optimal intervention time was 24 h. Compared with the pressure group, the DHJSD group presented significantly decreased expression of NLRP3, ASC, caspase-1, IL-1β, MMP-3, MMP-13, Adamts-4, and p62, and significantly increased expression of collagen II, aggrecan, Sox-9, PINK1, Parkin, and LC3. However, upon the addition of a mitophagy inhibitor, the protective effect of DHJSD on NP cells was diminished. Network pharmacology and molecular docking studies revealed that HIF-1α may be the key target of DHJSD in the treatment of IDD. Imaging and histopathological results confirmed that DHJSD delayed IDD progression. Western blotting and immunohistochemistry revealed that DHJSD increased HIF-1α expression, regulated mitochondrial division and fusion, and inhibited the activation of the NLRP3 inflammasome and subsequent inflammatory reactions.

DHJSD exerts a protective effect on NP cells by suppressing the activation of the NLRP3 inflammasome and subsequent imbalance in the extracellular matrix via mitophagy, which is potentially associated with the activation of the HIF-1α signaling pathway and the preservation of the metabolic balance of the mitochondria.

This study aimed to characterize the relationship between the superficial branches of the middle hepatic vein (MHV) and the gallbladder bed. This was achieved by assessing their proximity, transverse diameter, and contact length using computed tomography (CT) and cadaveric studies. The goal was to identify anatomically high-risk venous configurations that may be vulnerable during cholecystectomy, based on combined imaging and cadaveric findings.

A retrospective analysis was performed on 473 potential liver donors who underwent multiphase CT angiography between August 2017 and January 2025. After exclusions, 457 patients were included, and 57 patients whose vascular structures were located within 1 mm of the gallbladder bed were selected for detailed evaluation. The measurements included the transverse diameter and longitudinal contact length of superficial venous branches adjacent to the gallbladder fossa, along with their segmental topography. To anatomically validate the radiological findings, 15 formalin-fixed cadavers were dissected. The differences in detectability between CT imaging and cadaveric dissection were also evaluated.

Superficial MHV branches were identified adjacent to the gallbladder bed in all selected patients, with a mean transverse diameter of 2.99 ± 1.06 mm and a mean contact length of 9.24 ± 4.41 mm. Most veins followed segment V-related trajectories (73.7%), whereas segment IV-related courses (26.3%) were less common, with no significant differences in morphometric measurements between the groups. Contact length was positively correlated with venous diameter. Portal vein variations were significantly associated with hepatic segmental anatomy (P = 0.025) but were not directly relevant to routine cholecystectomy. The cystic artery configuration was not significantly associated with sex (P = 0.442). Cadaveric dissection confirmed the MHV drainage patterns but also demonstrated that very small venous branches may fall below the detection threshold of CT imaging.

Superficial MHV branches frequently course in close proximity to the gallbladder bed. Preoperative imaging may enhance anatomical awareness and optimize the surgical plan. The proximity, contact length, and topographical patterns of these veins should be considered anatomical risk indicators rather than definitive predictors of vascular injury. These findings support the role of detailed preoperative imaging in improving surgical safety and anatomical comprehension.

The lower trapezius musculocutaneous flap (LTMF) is a workhorse flap for the reconstruction of soft-tissue defects of the head and neck. However, when harvesting a large LTMF to repair massive defects, primary closure of the donor site may be challenging. This study aimed to evaluate the feasibility and safety of using a perforator propeller flap (PPF) for primary closure of LTMF donor sites and to analyze the buddy flap donor-site closure strategies through a comprehensive literature review.

We retrospectively reviewed data from patients who underwent LTMF donor-site defect reconstruction using PPF between January 2015 and October 2025. Data on patient demographics, defect features, flap characteristics, postoperative complications, and outcomes were collected and analyzed. In addition, a comprehensive literature search was conducted in PubMed, Embase, Scopus, and Web of Science to identify studies published before October 9, 2025, describing the use of an additional flap to close the donor site of a primary flap.

Seventeen patients underwent donor-site reconstruction of LTMFs using PPFs. The harvested LTMFs measured an average of 29.8 × 11.5 cm. The PPFs measured an average of 15.7 cm in length and 5.9 cm in width. All donor sites were closed primarily, and all PPFs survived completely. Complications occurred in three cases, including two cases of distal partial necrosis of the LTMF and one wound dehiscence at the LTMF donor site. The distal necroses were managed with debridement followed by secondary local flap reconstruction, whereas the wound dehiscence healed after conservative treatment. In the literature review, 43 studies comprising 547 cases were identified. Three reconstructive categories were established: Type 1 (locoregional flap), Type 2 (distant pedicled flap), and Type 3 (free flap) donor-site closures. Primary closure was achieved in 97.1% of patients, with an overall complication rate of 15.4%. Commonly adopted donor-site closure techniques for harvesting large flaps from different anatomical regions were summarized, providing a comprehensive overview of region-specific reconstructive strategies and their clinical outcomes.

The PPF provides a safe and effective option for achieving primary closure of large LTMF donor sites. Using one flap to reconstruct the donor site of another large flap represents a reliable and versatile approach that facilitates primary closure while minimizing donor-site morbidity and adhering to the “like-with-like reconstruction” principle.

Conversion therapy offers a critical opportunity to convert potentially resectable hepatocellular carcinoma (HCC) to surgically resectable status; yet, its optimal protocol and efficacy remain unstandardized and controversial. As a first-line systemic treatment for advanced HCC, immunotherapy combined with targeted therapy has demonstrated robust antitumor activity. Accumulating evidence suggests that radiotherapy can render some unresectable HCC patients amenable to surgical resections. Given these advancements, this study aims to investigate the efficacy and safety of cadonilimab (a dual immune checkpoint inhibitor targeting PD-1 and CTLA-4) plus lenvatinib (a multi-targeted tyrosine kinase inhibitor) combined with stereotactic body radiotherapy (SBRT), with the goal of achieving conversion therapy for potentially resectable HCC and prolonging survival for unresectable HCC.

This is a single-arm, single-center exploratory cohort study designed to enroll 27 HCC patients who meet the following eligibility criteria: surgically unresectable China Liver Cancer Staging (CNLC) stage Ia, Ib, or IIa, or surgically resectable CNLC stage IIb or IIIa. Eligible patients will undergo comprehensive tumor evaluation at three key time points: pre-conversion therapy (cadonilimab + lenvatinib + SBRT), after the second treatment cycle, and preoperatively. Postoperatively, patients will be followed up every six weeks for long-term efficacy and safety monitoring. The primary endpoint is the objective response rate (ORR), assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST) criteria; in case of inconsistent results between the two criteria, mRECIST will serve as the primary reference. Secondary endpoints include surgical resection rate, major pathological response (MPR) rate, duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), time to disease progression (TTP), overall survival (OS), and the incidence and severity of treatment-related adverse events (AEs). AEs will be graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and coded using the Medical Dictionary for Regulatory Activities (MedDRA), respectively.

This study is designed to evaluate the efficacy and safety of cadonilimab combined with lenvatinib and SBRT for conversion therapy in patients with potentially resectable HCC. By integrating dual immune checkpoint inhibition, anti-angiogenic targeted therapy, and high-precision local radiotherapy, this regimen leverages synergistic antitumor effects to address the unmet clinical need for optimized conversion strategies in HCC. This exploratory trial will provide critical clinical evidence for this novel triple-combination conversion therapy, enriching treatment options for patients with potentially resectable or technically unresectable HCC. The findings are expected to lay a solid foundation for future large-scale, multi-center randomized controlled trials to further validate the clinical value of this regimen.

Chinese Clinical Trials Registration No. ChiCTR2300068781.