The sequential monitoring of two pathological processes has clinical significance for early detection of drug-induced acute kidney injury (AKI), but remains challenging due to the lack of spatiotemporal probes. Here, we developed a hydrogen peroxide (H2O2) and myeloperoxidase (MPO) programmable responsive magnetic resonance imaging (MRI) probe (PAH-Gd) for spatiotemporal monitoring of renal oxidative stress and inflammation. Upon exposure to H2O2, PAH-Gd transformed into a kidney-targeting moiety, H-Gd, which selectively accumulated in kidneys and moderately enhanced renal T1-weighted imaging (T1 WI) signal. Subsequently, the H-Gd could be oxidized by MPO to form dimers or adducts with nearby proteins, further enhancing renal T1 WI signal. We found that PAH-Gd could perform spatiotemporal monitoring of renal oxidative stress and inflammation at 12 h and 24 h post-Cisplatin (DDP) administration, enabling early detection of DDP-induced AKI at least 60 h earlier than that of standard clinical assays and permitting dynamic monitoring of renal injury progression. The spatiotemporal T1 WI overcame the limitations in detecting diverse pathological processes with a single MRI probe, accurately reporting the drug-induced AKI in the early stage and contributing to AKI prevention and treatment in the clinic.
Background:Esophageal cancer (EC) lacks robust biomarkers to guide prognosis and therapy. Histone chaperone-related genes (HCRGs) shape chromatin states, but their roles in EC remain unclear. We integrated histone chaperone-based transcriptomic stratification with two-sample Mendelian randomization (MR) to identify genes with genetic evidence consistent with EC susceptibility and clinical relevance. Methods:RNA-seq and clinical data from TCGA-ESCA (184 tumors with available RNA-seq data and 13 normal samples) and an external cohort (GSE53624; 119 tumors, 119 normals) were analyzed. Prognosis-associated HCRGs informed unsupervised clustering. Differentially expressed genes common to cluster and tumor-versus-normal contrasts entered a two-sample MR framework using eQTL instruments and an EC GWAS (998 cases, 475,308 controls; European ancestry). Sensitivity analyses and the Steiger directionality test were then performed, followed by expression analysis to identify hub genes. We assessed survival associations, performed functional enrichment and immune deconvolution (CIBERSORT), modeled drug sensitivity (GDSC-based prediction), built a clinicogenomic nomogram, and validated expression by RT-qPCR in paired tissues. Results:HCRG-based clustering separated patients with distinct overall survival. MR implicated 26 genes in EC risk; among these, ADORA2B and SAPCD2 were consistently overexpressed in tumors (external validation and RT-qPCR) yet higher tumor expression predicted longer survival. Both genes were linked to cell-cycle and spliceosome programs; ADORA2B showed additional immuno-metabolic enrichment, whereas SAPCD2 mapped to metabolic/proteostasis pathways. High-expression groups exhibited reduced regulatory T-cell proportions and broader immune shifts. Predicted drug response suggested greater sensitivity to vinorelbine/etoposide but reduced sensitivity to paclitaxel in ADORA2B/SAPCD2-high tumors. A prognostic nomogram combining gene expression with stage and nodal status achieved 1-3-year AUCs of 0.67-0.75. Conclusions:Integrating HCRG-guided stratification with MR nominates ADORA2B and SAPCD2 as MR-supported biomarkers that are overexpressed in EC yet mark favorable prognosis, a pattern consistent with a less immunosuppressive microenvironment and distinct chemosensitivity. These genes warrant histology-stratified validation and mechanistic studies and may aid risk stratification and therapeutic decision-making.
The optimal surgical management of acute Rockwood type III acromioclavicular (AC) joint dislocations remains controversial. This study aimed to compare clinical and radiological outcomes among three techniques: hook plate (HP) fixation, isolated coracoclavicular (CC) suspension with a single endobutton, and combined AC and CC ligament reconstruction using two separate endobuttons. This retrospective cohort study included 69 patients who underwent surgical treatment for acute Rockwood type III AC joint dislocations between 2018 and 2024 at the mean follow-up of approximately 24 months. Patients were divided into three groups: hook plate fixation (Group A, n = 29), single endobutton CC fixation (Group B, n = 18), and combined AC and CC reconstruction with two separate endobuttons (Group C, n = 22). Clinical outcomes were assessed using the Constant–Murley Score (CMS), American Shoulder and Elbow Surgeons (ASES) score, Visual Analog Scale (VAS), and time to return to daily activities and sports. Radiological evaluation included acromioclavicular distance (ACD) and coracoclavicular distance (CCD). All groups demonstrated significant improvement (p < 0.05) in CMS, ASES, and VAS scores from baseline to final follow-up, which refers to the last clinical and radiographic assessment at approximately 24 months postoperatively. At the final assessment, Group C demonstrated more favorable outcomes, with significantly higher CMS and ASES scores and a lower VAS score compared to Groups A and B (p < 0.05). Importantly, the observed improvements in all three scores exceeded the reported minimal clinically important difference thresholds across all groups. Radiologically, while CCD did not differ significantly among groups, ACD showed significant intergroup differences (p < 0.05), with Group C demonstrating better maintenance of AC joint reduction. Group C also demonstrated a lower complication rate descriptively and the shortest time to return to daily activities and sports (p < 0.05). All three surgical techniques were effective in treating acute Rockwood type III AC joint dislocations. Combined AC–CC reconstruction with two endobuttons offered superior maintenance of AC joint reduction versus isolated CC suspension, a lower complication rate trend than hook plate fixation, and faster return to activities. Radiographic advantages over hook plate fixation were not statistically significant, and CCD differences were non-significant across groups.
Objective: To compare the circumferential proportion of mucosal defects, defect length, and the length-to-residual mucosal proportion (LRP) index for predicting esophageal stricture after endoscopic submucosal dissection (ESD) in patients with mucosal defects ≥6 cm, and to explore LRP in defects >10 cm. Methods: This retrospective study included 378 patients undergoing esophageal ESD from February 2014 to June 2020, grouped by stricture status. LRP was defined as defect length divided by residual mucosal proportion, with residual mucosal proportion set at a lower bound of 0.05 for statistical calculation. Receiver operating characteristic analysis compared the three indicators, including subgroup analysis for defects >10 cm. Results: Postoperative stricture occurred in 82 patients (21.7%). Circumferential proportion, defect length, and LRP were higher in the stricture group than in the non-stricture group (all p < 0.001). In the overall cohort, circumferential proportion and LRP showed comparable discrimination (AUC 0.877 vs. 0.876; p = 0.825), both outperforming defect length alone (AUC 0.694; both p < 0.001). In defects >10 cm, LRP showed the highest numerical AUC (0.913), followed by circumferential proportion (0.886) and defect length (0.668). Multivariable analysis confirmed that LRP was independently associated with stricture (per 10-unit increase: OR = 1.225; 95% CI, 1.150-1.304; p < 0.001). Conclusions: LRP was comparable to circumferential proportion and may serve as an exploratory complementary metric in long-segment defects, warranting external validation.
BACKGROUND The purpose of this study was to analyze the outcomes of revascularization exceeding 12 h after arterial injury at different sites of the lower extremity. MATERIAL AND METHODS From January 2009 to April 2017, 58 patients with 58 lower-limb arterial injuries who underwent revascularization over 12 h after trauma were included in our study. Outcomes measured, including mortality, amputation, complications, and other parameters (gait, length discrepancy, the range of movement of the knee and ankle joint, and muscle wasting) were analyzed. RESULTS External iliac artery injury (EIAI) or femoral artery injury (FAI) was affected in 4 patients, superficial femoral artery injury (SFAI) in 18, and popliteal artery injury (PAI) (including proximal gastrocnemius muscle vascular (PGMV) and proximal gastrocnemius muscle vascular [PGMV]) in 36. The median time of arterial injury was 72 h (interquartile range, 59.5). No mortality was found. Amputations were performed in 16 patients due to non-viable limbs, progressing infection, or muscle necrosis. All patients were followed up (median, 52 months; interquartile range, 5.5). Of the 42 limb-salvage patients, most had a limp, muscle wasting, or ankle and knee dysfunctions, and 26 patients with knee or ankle dysfunction underwent secondary surgery. CONCLUSIONS Although limited recanalization of blood vessels may lead to limb complications or amputations over time, the high success rate of limb salvage still merits the surgeon's best efforts.
Background and Aims Rectal neuroendocrine tumors (r-NETs) 10-20 mm in size may be treated endoscopically, and R0 resection is critical. We describe a modified traction-assisted snare technique using a shortened external cannula for an r-NET. (Fig. 1) Methods A 70-year-old man with an 11-mm rectal submucosal lesion underwent staging with contrast-enhanced CT and endoscopic ultrasound, confirming a well-demarcated submucosal tumor without muscular invasion or metastasis. Resection was performed using a shortened external cannula mounted with a snare and foreign-body grasping forceps to provide controlled traction and a stable resection plane. Results The lesion was completely drawn into the cannula and removed en bloc with a traction-assisted snare, followed by clip closure of the mucosal defect. Total procedure time was approximately 7 minutes, with no immediate adverse events or delayed complications. Histopathology confirmed a grade 1 r-NET with negative lateral and vertical margins, consistent with R0 resection. Conclusions External cannula–assisted traction snare resection enabled rapid, safe R0 removal of an intermediate-sized r-NET and may represent a simple alternative to more complex techniques for selected submucosal r-NETs.
BACKGROUND:Endoscopic resection (ER) is the main treatment for T1 superficial esophageal cancer (SEC). Additional surgical resection (ASR) is recommended to improve the prognosis of patients with non-curative resection who are at high risk of recurrence and metastasis. However, the survival benefit of ASR compared to non-ASR remains unclear. We conducted a systematic review and meta-analysis to quantify the survival benefits of ASR versus non-ASR, providing robust data for clinical decision-making. METHOD:We searched PubMed, Cochrane, Embase, and Web of Science databases for studies published before 24 February 2025. The primary outcome was overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS). Two independent reviewers screened and extracted the data and resolved disagreements by consensus. Risk of bias was assessed with Newcastle-Ottawa Scale. RESULTS:The review identified 15 retrospective studies involving 1348 patients. Analysis showed that patients with ASR had significant survival advantages over non-ASR patients in OS, RFS, and DSS. Hazard ratios (HRs) with 95% confidence intervals (CIs) were as follows: OS (HR = 3.06; 95% CI: 2.11-4.43), RFS (HR = 1.68; 95% CI: 1.16-2.41), and DSS (HR = 4.11; 95% CI: 1.64-10.28). Survival curves indicated that at 3, 5, and 10 years, the OS rates were 95.9% versus 88.0%, 91.4% versus 78.2%, and 86.7% versus 56.9% for the ASR and non-ASR groups, respectively. Similarly, the RFS rates were 93.4% versus 82.9%, 83.6% versus 73.8%, and 74.5% versus 57.5%. For DSS, the rates were 98.4% versus 94.5%, 97.8% versus 91.1%, and 97.8% versus 87.9%. Log-rank tests confirmed significance for all comparisons except 10-year DSS. CONCLUSIONS:For patients with T1 SEC who had non-curative ER, ASR therapy provides advantages over non-ASR therapy. However, within 5 years, the DSS difference between the ASR and non-ASR groups is likely to be minimal, with a range of approximately 4-6%.
Background: Immunogenicity activation is vital for radioimmunotherapy, but the short-term oxidative damage caused by precise radiation planning limits this effect. Chemodynamic therapy (CDT) with prolonged generation of hydroxyl radical (•OH) can initiate immunogenicity in combination with X-rays, however, its performance is constrained by tumor insufficient H2O2. Methods: Here, we propose to construct β-lapachone-based nanoparticles (β-Lap/Fe NPs) which initiate cascade reactions to generate high levels •OH for an extended period in tumor following X-ray irradiation. Results: β-Lap/Fe NPs, constructed by co-encapsulation of β-Lap and Fe3O4 nanoparticles in reactive oxygen species (ROS) responsive C16-S-mPEG2000 micelles, remain stable under normal conditions but rapid decompose and release β-Lap and Fe2+ when exposed to high level ROS. Upon X-ray irradiation, the upregulation of ROS and NAD (P) H: quinone oxidoreductase-1 (NQO1) in tumor cells accurately triggers β-Lap/Fe NPs to persistently generate high levels H2O2 and •OH for 12 hours, ultimately causing strong immunogenic cell death effects. Moreover, β-Lap/Fe NPs with excellent T2-weighted magnetic resonance imaging provide imaging reference for guiding precise X-ray radiation and predicting •OH generation. β-Lap/Fe NPs mediated radio-chemodynamic-immunotherapy remarkably against primary tumor growth, and further shows effective suppression on untreated distant tumors via the abscopal effect. Conclusions: In a word, this work proposed the simple but powerful strategy for cancer radio-chemodynamic-immunotherapy that combines X-ray and CDT to remote locally and visually actuated long-time production of H2O2 and subsequently persistent generation of •OH for initiating strong antitumor immune responses.
Adverse events, such as postoperative pneumonia, can occur in some patients after esophageal endoscopic submucosal dissection (ESD). However, few studies have investigated it. As such, we aimed to develop a nomogram to evaluate the progression of postoperative pneumonia after esophageal ESD. Between January 2014 and November 2023, this multicenter retrospective study enrolled patients received esophageal ESD. Data from 492 patients who underwent esophageal ESD were collected for model development. Clinical features and procedure-related characteristics were analyzed. A novel nomogram was constructed based on the results of multivariable logistic regression analysis. Besides, data from 226 and 101 patients were collected for internal and external validation, respectively. Subsequently, the discrimination, calibration, and clinical practice ability of the nomogram were evaluated. The incidence of postoperative pneumonia after esophageal ESD was 18.6
Osteosarcoma is the most common primary bone tumor with a high metastatic rate. Despite the improvement in patient prognosis with conventional therapeutics, enhancing the survival of patients with metastatic disease remains a challenge. Zoledronic acid (ZOL) stimulates apoptosis in cancer cells and is considered a promising drug for osteosarcoma therapy. Moreover, depletion of Inhibin Subunit Beta A (INHBA), a member of the transforming growth factor superfamily, can suppress osteosarcoma cell proliferation and invasion. Regarding the restricted potential of monotherapy, combination therapies, such as small interfering RNA (siRNA) and chemotherapy, are ideal strategies. However, off-target effects and adverse impacts lead to unsatisfactory clinical efficacy of these drugs. To address this challenge, we designed a folic acid-modified macrophage membrane coated with a carbon quantum dot (CQD) nanoplatform for the co-delivery of ZOL and siINHBA (ZOL-siINHBA@CQD@RM-FA). The anticancer activity of this nanotherapeutic agent was examined in vitro and in vivo. ZOLsiINHBA@CQD@RM-FA was approximately 200.7 nm in size, had a negative charge, excellent pH responsiveness, desirable biocompatibility, and high cellular uptake. This nanosystem achieved favorable co-delivery of ZOL/siINHBA and impaired osteosarcoma proliferation and invasion in vitro. Notably, intravenous administration facilitated tumor growth regression and inhibited lung metastasis without systemic toxicity. Accordingly, this nanotherapy could be considered an effective treatment for osteosarcoma, and this nanodelivery system shows potential for combined therapy by co-delivering genes and chemotherapy drugs.
The increasing detection of submucosal tumors (SMTs) in the upper gastrointestinal tract (UGI) is due to the increased clinical use of endoscopy and imaging technology. Some of these SMTs have malignant potential and may cause clinical symptoms. Thus, it is recommended in clinical guidelines to consider resection of these SMTs. Endoscopic techniques have become widely used in the diagnosis and treatment of SMT in the UGI as compared with traditional surgery due to their advantages of minimally invasive, quick recovery, and economical cost. Recently, new endoscopic techniques and instruments have been continuously implemented, leading to revolutionary innovation in endoscopic treatments. However, the safety and efficacy of these innovative techniques remain unclear. Therefore, we have comprehensively summarized the various techniques used in the treatment of UGI tumors in recent years, evaluated the indications and effects of each technique, and compared their benefits and disadvantages. We hope that this review will provide a more comprehensive reference for clinical and endoscopic practitioners, and help them develop more individualized treatment plans for different patients. This will ultimately expand the patient population that can benefit from these innovative technologies.
BACKGROUND:Delayed reduction of displaced pelvic ring fractures poses considerable surgical challenges. This study aimed to assess the reduction timing and effectiveness of various reduction strategies for delayed treatment of Tile C pelvic ring fractures. MATERIALS AND METHODS:Between January 2020 and September 2023, 38 patients with Tile C type pelvic ring fractures, including 4 type C1, 16 type C2, and 18 type C3, underwent delayed reduction (more than a 10-day interval from injury to surgery) through different techniques, were retrospectively reviewed. Intraoperatively, closed reduction using Schanz pin traction or the Starr Frame-assisted Unlocking Closed Reduction Technique (UCRT) were preferred. If the above closed reduction fails, open reduction by using lumbo-iliac pedicle screw system was forced. The reduction quality was radiographically assessed according to Matta Pelvic Score. And the lower-extremity functionality was clinically evaluated by Majeed function score standard. RESULTS:The 38 patients underwent a follow-up period ranging from 18 to 41 months. Closed reduction was successfully accomplished in 24 cases. Among these, two cases (type C1-1 and C1-2) achieved excellent reduction through the employment of Schanz pins technique. Additionally, 22 cases (comprising 2 of type C1-2, 16 of type C2, and 4 of type C3) that underwent UCRT resulted in excellent reduction for 11 patients, good reduction for 8 patients, and fair reduction for 3 patients. Following the failure of closed reduction, 14 patients with type C3 fractures underwent conversion to open reduction, and subsequently achieved excellent reduction. All patients achieved bony union (mean, 4.34 months). According to the average Majeed functional score, the lower-extremity functionality was deemed excellent in 2 patients using Schanz pins technique, 12 patients via UCRT and 9 patients by means of open reduction; good in 9 patients utilizing UCRT and 5 patients undergoing open reduction; and fair in 1 patient employing UCRT. In three cases, sensory nerve damage occurred, with a later complete recovery. CONCLUSION:For Tile type C pelvic fractures, early surgical intervention (within 10 days post-injury) may allow superior closed reduction outcomes. The Schanz pin technique appears well-suited for minimally displaced Tile C1-1/C1-2 pelvic fractures. The UCRT technique demonstrates favorable reduction outcomes in Tile C1/C2 fractures, whereas its effectiveness is comparatively limited in the management of C3 injuries. In such complex cases, particularly when UCRT fails, the ilio-lumbar pedicle screw technique offers a reliable alternative.
Immune cells distinguish cancer cells mainly relying on their membrane-membrane communication. The major challenge of cancer vaccines exists in difficult identification of cancer neoantigens and poor understanding over immune recognition mechanisms against cancer cells, particularly the combination among multiple antigens and the cooperation between antigens and immune-associated proteins. We exploit cancer cell membranes as the whole cancer antigen repertoire and reinforce its immunogenicity by cellular engineering to modulate the cytomembrane's immune-associated functions. This study reports a vaccine platform based on radiation-engineered cancer cells, of which the membrane HSP70 protein as the immune chaperon/traitor is endogenously upregulated. The resulting positive influences are shown to cover immunogenic steps occurring in antigen-presenting cells, including the uptake and the cross-presentation of the cancer antigens, thus amplifying cancer-specific immunogenicity. Membrane vaccines offer chances to introduce desired metal ions through membrane-metal complexation. Using Mn2+ ion as the costimulatory interferon genes agonist, immune activity is enhanced to further boost adaptive cancer immunogenicity. Results have evidenced that this artificially engineered membrane vaccine with favorable bio-safety could considerably reduce tumorigenicity and inhibit tumor growth. This study provides a universally applicable and facilely available cancer vaccine platform by artificial engineering of cancer cells to inherit and amplify the natural merits of cancer cell membranes.
Introduction Endoscopic submucosal dissection(ESD)has evolved into a viable treatment modality for early esophageal cancer,with a distinct advantage of the ability to perform en-bloc resection and accu-rate histopathological assessment.The most common adverse events of ESD in the esophagus include perforation and stricture.In this report,we present a case of a rare complication of esopha-geal ESD,which happened during the procedure and was re-solved successfully based on our experience.
INTRODUCTION:Several studies have reported the role of Helicobacter pylori eradication in gastric cancer (GC) prevention. However, for individuals with unsatisfactory management of their H. pylori infection status after eradication, the risk of GC remains unclear. METHODS:An exhaustive search strategy of the incidence of GC (including primary gastric cancer and metachronous gastric cancer) incidence in patients with unsuccessful eradication or H. pylori reinfection was implemented in the PubMed, Embase, Cochrane Library, and Web of Science. The hazard ratios (HRs) and cumulative incidence of total GC in patients with failed eradication or H. pylori reinfection (FE-Hp (+)) group were compared with that in patients with successful eradication and no H. pylori reinfection (SE-Hp (-)) group and patients with noneradication (NE) group. RESULTS:Seven eligible studies (including 8,767 patients with H. pylori infection) were identified. In the FE-Hp (+) group, the total GC risk was 1.86-fold of that in the SE-Hp (-) group (HR = 1.86, 95% confidence interval [CI]: 1.14-3.04, P = 0.013). The total GC risk in the NE group was also higher than that in the FE-Hp (+) group (HR = 1.98, 95% CI: 1.11-3.52, P = 0.002). On further analysis with different end points showed that the pooled GC risk increased over time (5-year follow-up: HR = 2.92, 1.34-6.34; 10-year follow-up: HR = 4.04, 2.56-6.37). DISCUSSION:Compared with the SE-Hp (-) group, the FE-Hp (+) group had a higher risk of gastric carcinoma. Long-term monitoring of H. pylori infection status could consolidate the benefit of eradicating H. pylori for preventing GC prevention in patients after eradication.