Jiangmen Central Hospital

Endometriosis diagnosis is often limited by the resolution of conventional imaging techniques (ultrasound/non-targeted MRI) as well as the invasiveness and recurrence risks associated with laparoscopy. To overcome these challenges, we developed anti-MMP-9 peptide-conjugated NaGdF4@PEG-Cy5.5 nanoparticles (NPPCNs), which integrate NaGdF4 cores to enhance T1 relaxivity and biocompatibility for MMP-9-targeted molecular imaging.In vitrostudies confirmed both cytocompatibility and high-affinity MMP-9 binding.In vivobiodistribution, assessed through T1-weighted MRI and fluorescence imaging within 48h post-injection, revealed significant nanoparticle accumulation in endometriotic lesions, with elevated signal intensity compared to controls. This MMP-9-targeted theranostic platform offers a non-invasive method for lesion detection, providing a novel approach for precise diagnosis and surgical navigation in endometriosis.

The neoadjuvant chemoradiotherapy (nCRT) might accentuate surgical complications and toxicity in the treatment of locally advanced rectal cancer (LARC) while neoadjuvant chemotherapy (nCT) alone shows promise as an alternative treatment. However, which patients deserve most from the nCT need further clarify. This trial aimed to assess the non-inferiority of nCT with capecitabine plus oxaliplatin (CAPOX) versus nCRT with capecitabine in LARC with uninvolved mesorectal fascia (MRF). Patients with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to receive 4 cycles of CAPOX chemotherapy alone (nCT group) or CRT with concurrent Capecitabine (nCRT group). The primary end point is 3-year locoregional recurrence-free survival (LRRFS). Secondary end points, such as 3-year disease-free survival (DFS), 3-year overall survival (OS), and adverse events (AEs), were also reported. A total of 663 patients were enrolled and 589 patients received the allocated treatment (nCT, n = 300; nCRT, n = 289). LRRFS was analyzed with a median follow-up of 48 months. 3-year LRRFS was 97.4% (95% CI, 95.5 to 99.3) in the nCRT group and 96.3% (95% CI, 94.0 to 98.6) in the nCT group, resulting in a hazard ratio (HR) of 1.40 (95% CI, 0.53 to 3.68). The nCT and nCRT achieved similar 3-year DFS (89.2% v 87.9%; HR, 0.88 [95% CI, 0.54 to 1.44]) and 3-year OS (95.0% v 94.1%; HR, 0.86 [95% CI, 0.42 to 1.76]). The nCT group showed a lower incidence of grade 2 to 4 long-term AEs (16.0% v 26.3%, P = 0.002) and proctitis (33.6% v 41.7%, P = 0.049) compared with nCRT group. The non-inferiority of nCT was not confirmed with a very low incidence of local recurrence in both group. But nCT offers comparable DFS and OS while mitigating the burden of toxicity as compared to nCRT. These insights shed light on a potential paradigm shift in the treatment for LARC with uninvolved MRF.

30 to 70% of patients with positive sentinel lymph nodes (SLNs) in early breast cancer do not develop non-SLN metastases. They are exposed to the potential complications and sequelae of axillary lymph node dissection (ALND) without gaining additional therapeutic benefit. Therefore, a prediction model for non-SLN metastasis is needed. We identified the anatomical location of metastatic SLNs as a key factor for predicting non-SLN status. We retrospectively identified 1,717 consecutive patients who underwent SLN biopsy; 481 SLN-positive patients treated from 2009 to 2019 underwent completion ALND and formed the development cohort, and 113 SLN-positive patients treated from 2020 to 2022 served as a temporal validation cohort. A multivariable logistic regression model was developed and presented as a nomogram. Performance was assessed by discrimination and calibration, and clinical utility by decision curve analysis. The Memorial Sloan Kettering Cancer Center (MSKCC) and Shanghai Cancer Hospital (SCH) models were evaluated for comparison. Multivariate analysis revealed eight independent predictors of non-SLN metastasis: metastatic SLN location, tumor size, multifocality, lymphovascular invasion, extracapsular extension, number of positive and negative SLNs, and size of SLN metastasis. The nomogram based on these variables achieved high discrimination in both the training (AUC = 0.830) and validation (AUC = 0.785) cohorts. In the temporal validation cohort, discrimination was higher than the MSKCC model (AUC= 0.690; P = 0.033) and numerically higher than the SCH model (AUC = 0.716; P = 0.088). At prespecified false-negative rate targets, the model identified 0.9%, 23.0%, and 27.4% of patients as candidates for omitting completion ALND under FNR thresholds of 0%, <5%, and <10%, respectively, and yielded a higher net benefit than the comparator models across clinically relevant risk thresholds. The model also maintained performance in patients with ≥3 positive SLNs (AUC = 0.843). Metastatic SLN location relative to the ICBN is a novel anatomical predictor of non-SLN metastasis. A nomogram incorporating this variable demonstrated good discrimination and clinical utility in a single-center cohort with temporal validation; prospective multicenter validation with standardized ICBN assessment is warranted before broader implementation.

Stroke-associated infection (SAI) is a significant complication of stroke, with approximately 30% of stroke patients developing infections, primarily respiratory and urinary tract infections. These infections can severely impact prognosis and increase the economic burden. While dysphagia is a known independent risk factor for stroke-associated pneumonia, research shows that stroke patients without aspiration or related risk factors, such as dysphagia and impaired consciousness, also exhibit a high incidence of non-aspiration stroke-associated infections (NA-SAI). This comprehensive article meticulously examines and reviews the risk factors, pathophysiological underpinnings, and therapeutic strategies for NA-SAI, with the aim of enhancing clinicians' comprehension and management of this condition.

Abstract Objectives To test whether brief intermittent hypoxia (IH) induces early hyperexcitability and antioxidant imbalance in the primary auditory cortex (Au1), and whether high-dose vitamin C (VC) pretreatment mitigates these effects. Methods Adult male Sprague–Dawley rats were assigned to four groups (n = 6/group): control, IH, IH plus intraperitoneal normal saline (IH + IPNS), and IH plus intraperitoneal VC (IH + IPVC). Rats underwent a 3-h IH protocol; VC (500 mg/kg, i.p.) or saline was administered 30 min before IH. Three hours after IH, in vivo Au1 multiunit recordings quantified spontaneous firing rate (SFR). We quantified catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and assessed apoptosis using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Results Acute IH increased Au1 SFR versus control, and saline did not alter this response; VC pretreatment reduced SFR toward control levels. IH decreased CAT activity and increased SOD activity, with minimal change in GPx. VC increased CAT, SOD, and GPx activities relative to IH. No overt neuronal apoptosis was detected. Conclusions Brief OSA-relevant IH triggers an early stage of auditory cortical dysfunction with hyperexcitability and antioxidant imbalance. High-dose VC pretreatment attenuates hyperexcitability and enhances antioxidant enzyme activity, supporting antioxidant strategies as adjuncts for central auditory protection.

Recombinant human erythropoietin (rhEPO) fused with human immunoglobulin G (IgG) Fc fragment (rhEPO-Fc) is a novel erythropoiesis-stimulating agent designed to extend plasma half-life and enhance biological activity. However, data on the efficacy and safety of rhEPO-Fc in hemodialysis patients with chronic kidney disease (CKD)-related anemia remain limited. This phase 3 trial enrolled patients from 45 Chinese hospitals. Participants were randomized (2:1) to receive either rhEPO-Fc or rhEPO (Chinese hamster ovary cell-derived) for 28 weeks. The rhEPO-Fc responders were eligible for a 24-week extension period. The primary endpoint was the least square mean (LSM) change in hemoglobin (Hb) levels from baseline between weeks 21 and 28. Among 356 rhEPO-Fc and 178 rhEPO recipients, patients receiving rhEPO-Fc demonstrated non-inferiority Hb maintenance compared with rhEPO. The inter-group LSM differences in the full analysis set and per-protocol set were 3.96 g/L (95% CI: 3.02–4.89; p < 0.001) and 2.27 g/L (95% CI: 0.60–3.95; p = 0.008), respectively. Adverse drug reaction rates were comparable (rhEPO-Fc: 39.2% vs. rhEPO: 40.2%). Dose adjustments due to treatment-emergent adverse events were significantly lower with rhEPO-Fc (0.0% vs. 2.2%; p < 0.05). Deaths unrelated to the study drugs occurred in two rhEPO-Fc and four rhEPO patients. These findings indicated that rhEPO-Fc effectively maintained Hb levels in patients with CKD anemia undergoing hemodialysis, showing comparable efficacy to rhEPO with reduced dosing frequency and a similar safety profile.

The anti-PD-L1 antibody has been applied for use in first-line advanced biliary duct cancer patients. However, clinical evidence of toripalimab in combination with biweekly 5-fluorouracil (5-FU) is limited and predictive biomarkers of treatment benefits remain unclear. This prospective study enrolled patients with unresectable or metastatic BTC who received toripalimab in combination with gemcitabine and biweekly 5-FU. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). Secondary endpoints included overall survival (OS) and safety. Exploratory analyses evaluated associations between programmed cell death-ligand 1 (PD-L1) expression or tumor mutational burden (TMB) and clinical outcomes. A total of 30 patients were enrolled, with a median follow-up duration of 16.0 months. The ORR was 13.0%. The median PFS and OS were 5.3 months (95% CI: 3.59-7.01) and 11.7 months (95% CI: 6.07-17.33), respectively. Subgroup analyses revealed no significant association between PD-L1 status or TMB level and improved PFS. All patients experienced adverse events (AEs), while grade 3-4 AEs occurred in eight patients (26.7%), most commonly anemia (20.0%), leukocytopenia (13.3%), and nausea (6.6%). No grade 5 AEs were observed, and the safety profile was considered manageable. Toripalimab in combination with gemcitabine and 5-fluorouracil showed promising efficacy and was well-tolerated as a first-line therapy in advanced biliary duct cancer patients. Although PD-L1 expression and TMB did not predict treatment benefit, larger studies are needed to validate potential biomarkers and further optimize immunochemotherapy strategies for BTC.

Abstract Background The management of hyperphosphatemia in dialysis patients presents a clinical dilemma with nutritional status. This study investigated the association between serum albumin-to-phosphorus (A/P) ratio and all-cause mortality in peritoneal dialysis patients. Methods This multicenter retrospective cohort study, a total of 3,672 PD patients who met inclusion criteria from 11 Chinese PD centers from 1 July 1998 to 28 February 2023. Participants were stratified into tertiles based on A/P ratio levels. All patients were followed up until the endpoint event (all-cause death) or May 31, 2023. The clinical data of the three groups were compared, and the Kaplan-Meier method and Cox risk regression model were used to analyze the relationship between them. Results Among 3,672 participants, 2,044 (55.7%) were male, with a mean age of 50.8 ± 14.5 years and a median dialysis vintage of 56.8 (IQR 28.6–91.3) months. Based on A/P ratio tertiles, patients were categorized into: Low-level group (A/P &lt; 0.62, n = 1,224), Medium-level group (0.62 ≤ A/P ≤ 0.82, n = 1,224), High-level group (A/P &gt; 0.82, n = 1,224). Multivariate Cox analysis revealed the high A/P ratio was independently associated with increased all-cause mortality (HR = 1.009, 95% CI 1.0001.08-1.0172.41). The high-level group had significantly higher all-cause mortality (χ²=36.53, P &lt; 0.001). Conclusion In patients receiving PD, an elevated serum A/P ratio is independently linked to a heightened risk of all-cause mortality.

Objective Tislelizumab frequently induces cutaneous immune-related adverse events (cirAEs), among which Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are rare but potentially life-threatening cutaneous reaction. The clinical characteristics of SJS/TEN induced by tislelizumab remain unclear. Methods This systematic review aims to clarify the clinical manifestations, therapeutic interventions, and outcomes of tislelizumab-related SJS/TEN in Chinese patients. Published case reports of SJS/TEN induced by tislelizumab were systematically collected (up to 10 May 2025). A total of 21 articles and 22 patients were included. Results A total of 22 patients were included, consisting of 14 males and 8 females, aged 42–81 years, with a median age of 71 years and a mean age of 68.59 ± 9.10 years. Lung cancer was the most common primary disease, affecting 12 patients (54.55%). 7 patients were treated with tislelizumab alone, while 15 underwent combination therapy (chemotherapy, radiotherapy, or targeted therapy). The time from treatment initiation to SJS/TEN onset ranged from 12 to 138 days. 20 patients experienced pain to varying degrees, with early symptoms primarily manifesting as erythema and rash. Mucocutaneous involvement was observed in 12 patients, and fever occurred in 11 patients. After drug discontinuation and symptomatic supportive care, the symptoms of 20 patients improved. Two patients died - one of septic shock and another of acute coronary syndrome. Conclusions This indicates that tislelizumab-related SJS/TEN mostly occurs days to months after treatment. Clinical practice should strengthen the evaluation and monitoring of early cutaneous adverse reactions, with timely detection and intervention to ensure safe medication use for patients.