The decellularized extracellular matrices (d-ECMs) currently utilized to repair endometrial injuries are derived from three tissue sources, the endometrium (dE-ECM), placental amniotic membrane (dA-ECM), and urinary (dU-ECM). Notably, the structures of dU-ECM and dE-ECM are similar. These d-ECMs are derived from different tissues, and their specific roles in endometrial injury repair remain unclear. This study aimed to analyse the characteristics of the tissue microstructures and compositions to confirm specific differences among the three ECM types. And using a rat model of endometrial injury, the effects of all the matrices after implantation on the promotion of endometrial regeneration were analysed. After decellularization, dE-ECM had more residual active factors than the other two ECM types, while dA-ECM had significantly less DNA, α-Gal antigen components and extracellular matrix components than the other two groups. Although the three ECMs had no effect on the proliferation of stromal cells , dA-ECM may have increased the sensitivity of stromal cells to oestradiol (E2) responses. experiments confirmed the promotional effect of dA-ECM on endometrial regeneration. For example, the endometrial thickness, collagen deposition, endometrial tissue regeneration, vascular regeneration and pregnancy outcomes were significantly better in this group than in the other two groups. These findings might be associated with the excellent immune tolerance of dA-ECM. Therefore, when selecting a d-ECM for the treatment of endometrial injury, dE-ECM, which has the strongest tissue specificity, is not the preferred choice. Controlling the inflammatory responses in local lesions at the early stage may be a prerequisite for ECMs to exert their functions.
Previous studies have suggested that maternal dietary protein was associated with allergic diseases in offspring, but few studies have evaluated the influence of dietary protein patterns. This study aimed to explore the prospective association between maternal dietary protein patterns during pregnancy and the risk of infant eczema. A total of 713 mother-child pairs from a prospective cohort in Guangzhou, China were recruited. Maternal dietary protein was estimated using a validated face-to-face food frequency questionnaire at 20-28 weeks' gestation from 2017 to 2018. Dietary protein patterns were calculated based on the sources of protein. The data of infant eczema was assessed at 6 months of age using the symptom questionnaire of eczema. Logistic regression was carried out to examine the associations between maternal dietary protein patterns and infant eczema. The cumulative incidence of infant eczema at 6 months of age was 51.19%. Mothers of infants with eczema consumed more protein from poultry source during pregnancy than mothers of infants without eczema, while no statistical differences were observed in maternal intakes of protein from cereals and tubers, vegetables, fruits, red meat, fish and seafood, eggs, dairy, soybean, and nuts and seeds. Four dietary protein patterns were identified and termed poultry, plant, dairy and eggs, and red meat and fish. The cumulative incidence of eczema was 61.2, 45.8, 48.0, 51.4% for these four patterns, respectively. Compared to the poultry dietary pattern, the plant pattern and the dairy and eggs pattern were associated with a reduced risk of infant eczema, and the adjusted odds ratios (95% confidence interval) were 0.572 (0.330-0.992), 0.478 (0.274-0.837), respectively. No such association was observed for the red meat and fish dietary protein pattern. This is the first study that focused on the association between maternal dietary protein during pregnancy from a whole-diet perspective and infant eczema. Compared with the poultry dietary protein pattern, the maternal plant pattern and the dairy and eggs pattern during pregnancy were associated with a reduced risk of infant eczema.
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.
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery •
To evaluate the safety and preliminary efficacy of dose-modified regimen of 5-fluorouracil plus oxaliplatin and irinotecan (mFOLFOXIRI) for patients with advanced colorectal cancer (CRC). Data of 312 CRC patients confirmed by pathology receiving triplet drug alone or combined with target therapy between October 2012 and December 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. CRC patients who had previously completed adjuvant therapy (or neoadjuvant therapy) within 6 months or palliative chemotherapy were excluded, meanwhile those with poor general condition (ECOG score > 2) or grade 2 neuropathy and allergy to oxaliplatin were excluded as well. Regimen of mFOLFOXIRI: oxaliplatin 85 mg/m² dissolved in 5% glucose solution 500 ml by intravenous infusion for 2 h; irinotecan 150 to 165 mg/m² dissolved in 0.9% sodium chloride 250 ml by intravenous infusion for 90 min; following intravenous infusion of leucovorin 400 mg/m² for 2 h, day 1; 5-FU 2800 mg/m², 48-h continuous intravenous infusion; once every 2 weeks. Therapy could be combined with a targeted drug, bevacizumab 5 mg/kg every two weeks; cetuximab 500 mg/m² every two weeks. Side effect was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 4.0.3). The objective response rate was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) after administering at least four cycles of chemotherapy. The median age was 52 years (range 16-73) in the whole group; 113 patients (36.2%) had locally advanced CRC, and 199 (63.8%) had metastatic CRC. Most patients (274/312, 87.8%) did not receive any treatment earlier. There were a total of 1651 chemotherapy cycles in the whole group, with a median of 6(1-19) cycles. Of these 1651 cycles, 124 cycles of chemotherapy(7.5%) were dose-adjusted; 176 cycles of chemotherapy(10.7%) were delayed for median 5(3-13) days; 124 cycles(7.5%) required dose decrease. The overall relative dose intensity was >90%; the specific drug dose intensity was 93.6%(2620 mg×m⁻²×d⁻¹) for fluorouracil, 97.8%(83 mg×m⁻²×d⁻¹) for oxaliplatin, and 94.2%(155 mg×m⁻²×d⁻¹) for irinotecan. Twenty-three patients (7 of intestinal perforation, 7 of intestinal obstruction, 1 of grade 4 hematologic toxicity, and 8 of grade 3 fatigue) refused subsequent chemotherapy due to intolerable toxicity. Main grade 3 or 4 adverse events in patients were neutropenia in 69 cases (22.1%), fatigue in 35 cases (11.2%), and anemia in 28 cases (8.9%). Twenty serious adverse events (6.4%) occurred, including 13 patients of febrile neutropenia (4.2%), 7 patients of intestinal perforation (2.2%, 4 patients in upper rectum, 2 in sigmoid colon, and 1 in transverse colon cancer), and 9 of them had subsequent sepsis (2.9%). All the patients with intestinal perforation underwent emergency operation. No treatment-related deaths occurred. In 199 patients with metastatic CRC, because 22 patients did not receive image evaluation, the preliminary efficacy of 177 patients was actually evaluated. A total of 113 objective response events were observed. The overall response rate was 63.8%(113/177), partial response rate was 61.6%(109/177), clinically complete response rate was 2.3%(4/177), stable disease was 29.9% (53/177), progressive disease was 6.2%(11/177), and the disease control rate was 93.8%(166/177). In 127 patients receiving triplet drug, objective response rate was 40.9% for those with less than four cycles and 81.1% for those with more than four cycles (P<0.001). The mFOLFOXIRI regimen with reduced dose can be safely used in advanced CRC and has achieved promising results in terms of short-term efficacy.
