The development of standardized cross-species evaluation frameworks is urgently needed for absorbable extracellular matrix (ECM) meshes, due to significant variations in safety and efficacy across tissue sources. This study establishes a multi-dimensional assessment system to quantify material-specific bio-functional correlations. Three ECM meshes-human acellular dermis (HAD), porcine acellular dermis (PAD), and porcine small intestinal submucosa (SIS)-were systematically characterized using integrated in vitro and in vivo analyses. Assessments included physicochemical properties (e.g., degradation kinetics via collagenase digestion), immunogenic residues (α-Gal epitopes and DNA quantification), and biocompatibility. In vivo performance was evaluated using rabbit subcutaneous (for degradation and immune response) and rat abdominal defect models (for macrophage polarization: CD206⁺/CD86⁺ ratio and collagen deposition). HAD exhibited superior structural stability (82.3% ± 1.2% residual mass after 7-day collagenase digestion), whereas SIS degraded most rapidly (10.5% ± 0.42%; p < 0.01 vs PAD) but provoked severe foreign body reactions (2.3-fold higher vs HAD at 13 weeks, p = 0.017). Notably, HAD uniquely promoted sustained M2-dominant macrophage polarization (CD206⁺/CD86⁺ ratio = 2.1 vs SIS = 0.7), which reduced inflammation and enhanced collagen remodeling (p < 0.05 vs SIS). Serum metabolomic analysis indicated that ECM mesh implantation induced a reprogramming of host amino acid metabolism, marked by a notable acceleration in L-methionine metabolism. The proposed integrated evaluation framework successfully identifies material-specific correlations among degradation behavior, immune response, and metabolic regulation, providing critical benchmarks for the rational design of immunomodulatory ECM meshes.
Transcatheter aortic valve replacement (TAVR) has emerged as an effective therapy for inoperable patients with severe aortic stenosis (AS). However, calcification-induced limited durability restricts its application. Fish swim bladders (FSB), which are resistant to calcific degeneration, offer a viable solution to this challenge. In this study, we developed a new TAVR device using FSB as the valve leaflet. Furthermore, the in vitro durability, in vivo performance, and size selection of this TAVR device were assessed by an experimental study and finite element analysis. A self-expandable TAVR device was fabricated by suturing the FSB films into a 23 mm nitinol alloy frame. Further, hemodynamic performance, such as effective orifice area, transvalvular pressure difference and regurgitant fraction, the durability was tested by the pulsatile flow test and accelerated fatigue test, according to the ISO 5840-3. The effect of release size on hydrodynamic performance was also investigated. Finally, the in vivo performance of the TAVR device were examined using a porcine implantation model. The results showed that the strength of the FSB films satisfied the requirements for valve leaflets. The hemodynamic performance of the FSB TAVR device met the requirements of ISO 5840-3 standards. After 400 million cycles, the FSB showed no fiber loss, torn, perforation, or other valve failure phenomena. In porcine models, the devices were well-positioned, functioned well with no stenosis immediately after the operation. Collectively, we successfully developed a TAVR device with FSB as valve leaflets that exhibited good fatigue resistance. STATEMENT OF SIGNIFICANCE: The source of material for the leaflets of commercialized biological heart valves (BHVs) is mainly bovine pericardium, but this material suffers the following problems: large and uneven thickness of the material, the presence of α-Gal and Neu5Gc antigens, and the susceptibility to structural valve degradation (SVD). New material for BHVs leaflets is rarely reported. In this study, we prepared a transcatheter aortic valve (TAV) and performed long-term in vitro and short-term in vivo studies using fish swim bladder (FSB) as the leaflets. The study confirmed that FSB TAV device can complete 400 million fatigue tests and maintain the good morphology of the leaflets, and that it still maintains good functionality after a certain amount of compression, indicating that FSB is a promising material for leaflets.
Over the past decades, red meat allergy, also known as mammalian meat allergy, which manifests differently from classic food allergies, has been reported in different countries and regions, including China. The allergen of this disease is not a protein but an oligosaccharide: galactose-α-1,3-galactose, i.e., alpha-gal or α-gal. Therefore, this clinical syndrome is also called α-gal syndrome (AGS). It clinically manifests as delayed anaphylaxis, i.e., patients generally develop allergic symptoms 2-6 h after ingesting red meat. This clinical manifestation is believed to be related to sensitization to α-gal after tick bites. Sensitized individuals may also develop anaphylaxis after ingesting food and medicine or being exposed to medical equipment containing α-gal, such as cetuximab and gelatin. Here, the literature on AGS is reviewed for a better understanding of its pathogenesis, clinical diagnosis, and treatment.
Histo-blood group antigens (HBGAs) have been found to be important host susceptibility factors or receptors for human rotavirus (RVs) with genotype-specific host ranges, impacting the disease patterns, epidemiology, and strategy development against RV diseases in humans. However, how the glycan factors contribute to RV diversity and host ranges to different animal species remains unclear. In this study using recombinant VP8* proteins as probes to perform glycan array analyses of RVs, we observed a wide range of glycan-binding profiles, including those binding to sialic acid-containing glycans, among group A (RVA) and group C (RVC) RVs that mainly infect different animal species. A tri-saccharide glycan Galα1-3Galβ1-4Glc containing a terminal α-Gal was recognised by multiple RVA/RVC genotypes, providing valuable information on RV evolution under selection of the step-wisely synthesised HBGAs in many animals before they were introduced to humans to be human pathogens. Saliva binding studies of VP8* also revealed strain-specific host ranges or species barriers between humans and these animal RV genotypes, further improved our understanding on RV host ranges, disease burdens, epidemiology, and vaccine strategy against RVs.
The 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX) regimen is the standard first-line treatment for metastatic colorectal cancer (mCRC), however, the optimal second-line regimen for KRAS wild-type mCRC patients is still investigational. In this study, we aimed to determine the clinical efficacy and safety of CMAB009 plus irinotecan compared to irinotecan-only as a second-line regimen for treating KRAS wild-type mCRC patients. Patients with KRAS wild-type mCRC who had previously failed to respond to FOLFOX treatment were randomly assigned in a 2:1 ratio, to receive CMAB009 plus irinotecan or irinotecan-only. Patients receiving irinotecan-only were permitted to switch to CMAB009 therapy on disease progression and were grouped as the sequential-CMAB009 arm. The primary endpoints were overall response rate (ORR) and median progression-free survival (PFS). The secondary endpoints were median overall survival (OS), disease control rate (DCR), clinical benefit rate (CBR), and duration of response (DOR). The CMAB009 plus irinotecan arm demonstrated significantly improved ORR (33.2% vs. 12.8%; P < 0.001) and longer median PFS (169 days vs. 95 days; P < 0.001) as compared to the irinotecan-only arm. Patients receiving CMAB009 plus irinotecan also demonstrated improved DCR (80.1% vs. 65.2%, P < 0.001), CBR (30.0% vs. 14.6%, P < 0.001), and DOR (210 days vs. 109 days; P < 0.001) as compared to irinotecan-only. However, patients treated with CMAB009 had an increased risk of skin rash (66.9% vs. 5.5%, P < 0.001) and paronychia (9.8% vs. 0.0%, P < 0.001). Anti-drug antibodies (ADA) were detected in 3.6% of patients, and only 0.9% of patients who received CMAB009 experienced hypersensitivity reactions. In patients receiving sequential-CMAB009 therapy after failure with irinotecan, their median PFS was 84 days (95% CI 65 to 113 days). The median OS was 425 days for patients receiving CMAB009 plus irinotecan and 401 days for those with sequential-CMAB009 (P = 0.940). Treatment with CMAB009 plus irinotecan was found to be a superior second-line regimen in comparison to irinotecan-only in KRAS wild-type mCRC patients. Further, switching to CMAB009 can be considered as an efficient third-line of treatment after treatment failure with second-line irinotecan-only. Trial registration ClinicalTrials.gov: NCT01550055, retrospectively registered on March 9, 2012.
A novel delayed anaphylactic reaction to red meat, associated with tick bites and IgE antibodies against galactose-α-1, 3-galactose (α-gal), was reported in 2009 in the US, Australia and Europe. In this case, serum specific IgE to galactose-α-1, 3-galactose (>100 kU/L) and IgE to multiple non-primate mammalian proteins were positive. However, the pathogenesis of this disease remains unclear. We report the first case in Asia of delayed anaphylactic reaction to red meat, which was induced by bites from the hard tick, Hematophagous ixodidae. We confirmed the increased concentration of IgE reactive epitopes in non-primate mammalian organs, which may be rich in α-gal proteins in lymphatic and endothelial tissues. All confirmed ticks associated with this disorder in the literature and in our case belonged to the hard tick family. We hypothesize that hard tick saliva is enriched with blood-type substances, such as oligosaccharides, from the non-primate mammal victim's blood after days to weeks of blood sucking, which sensitizes humans through the injection route while blood sucking.
A polysaccharide Astragalus polysaccharide (APS) was obtained from the boiling water extract of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao. The results of gas chromatography (GC) indicated that APS consisted of l-rhamnose (l-Rha), d-xylose (d-Xyl), d-glucose (d-Glc), and d-galactose (d-Gal) in the molar ratio of 1:4:5:1.5. Its molecular weight was determined to be 3.01 × 10(5) by high-performance gel filtration chromatography. The results of (1)H NMR and (13)C NMR spectral analysis indicated that APS had a linear backbone mainly consisting of 1,3-linked β-d-Gal residues with insertion of β-Glc, 1,6-linked α-Gal, 1,5-linked β-Xyl, 1,4-linked β-Gal, β-d-Gal, 1,2-linked α-Rha, 1,2,4-linked α-Rha residues. HSQC spectrum indicated that C-2 and C-6 may link with H.
The aim of this study was to evaluate safety and efficacy of cetuximab combined with chemotherapy in Chinese patients with advanced non-small cell lung cancer (NSCLC). A retrospective analysis of clinical data was conducted in patients who were given cetuximab combined with chemotherapy in the department of respiratory medicine, Peking Union Medical College Hospital between June 2008 and July 2011. All patients signed the informed consent, and consented to offer clinical information. Twenty-two patients were enrolled in this study. Nine patients were alive up to analysis, and the longest survival was 28.9 months. The objective response rate (ORR), disease control rate (DCR), median progression free survival (PFS), and estimated least median overall survival (OS) were 36.4%, 59.1%, 5.3 months and 10.1 months, respectively. Results for the 16 patients treated as first line setting were 50.0%, 62.5%, 6.0 months and 10.1 months, respectively. The common adverse events included skin toxicity (14, 63.6%), alanine aminotransferase elevation (7, 31.8%), hematological toxicity (5, 22.7%), allergy (1, 4.5%) and fever (5, 22.7%). Cetuximab combined with chemotherapy for Chinese patients with advanced NSCLC had promising ORR, DCR, and PFS, especially in the first line subgroup. Serious adverse events had low incidence and were manageable.
