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Patients with advanced or metastatic oesophageal squamous cell carcinoma have poor prognosis and few treatment options after first-line therapy. We aimed to assess efficacy and safety of the anti-PD-1 antibody camrelizumab versus investigator's choice of chemotherapy in previously treated patients. ESCORT is a randomised, open-label, phase 3 study of patients aged 18 to 75 years with a histological or cytological diagnosis of advanced or metastatic oesophageal squamous cell carcinoma done at 43 hospitals in China. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had progressed on, or were intolerant to, first-line standard therapy. Patients were randomly assigned (1:1) to camrelizumab (200 mg every 2 weeks) or chemotherapy with docetaxel (75 mg/m2 every 3 weeks) or irinotecan (180 mg/m2 every 2 weeks), all given intravenously. Central randomisation was done using the Randomization and Trial Supply Management system with block size randomly generated as four or six and stratified by disease and ECOG performance status. The primary endpoint was overall survival, assessed in randomised patients who had received at least one dose of treatment. Safety was assessed in all treated patients. The trial is registered with ClinicalTrials.gov, NCT03099382, and is closed to new participants. From May 10, 2017, to July 24, 2018, 457 (75%) of 607 screened patients were randomly assigned to treatment, of whom 228 received camrelizumab treatment and 220 received chemotherapy. As of data cutoff on May 6, 2019, with a median follow-up time of 8·3 months (IQR 4·1–12·8) in the camrelizumab group and 6·2 months (3·6–10·1) in the chemotherapy group, median overall survival was 8·3 months (95% CI 6·8–9·7) in the camrelizumab group and 6·2 months (5·7–6·9) in the chemotherapy group (hazard ratio 0·71 [95% CI 0·57–0·87]; two-sided p=0·0010). The most common treatment-related adverse events of grade 3 or worse were anaemia (camrelizumab vs chemotherapy: six [3%] vs 11 [5%]), abnormal hepatic function (four [2%] vs one [<1%]), and diarrhoea (three [1%] vs nine [4%]). Serious treatment-related adverse events occurred in 37 (16%) of 228 patients in the camrelizumab group, and in 32 (15%) of 220 patients in the chemotherapy group. Ten treatment-related deaths occurred, seven (3%) in the camrelizumab group (three deaths from unknown causes, one enterocolitis, one hepatic function abnormal, one pneumonitis, and one myocarditis) and three (1%) in the chemotherapy group (two deaths from unknown causes, and one gastrointestinal haemorrhage). Second-line camrelizumab significantly improved overall survival in patients with advanced or metastatic oesophageal squamous cell carcinoma compared with chemotherapy, with a manageable safety profile. It might represent a potential option of standard second-line treatment for patients with oesophageal squamous cell carcinoma in China. Jiangsu Hengrui Medicine.

The addition of camrelizumab to gemcitabine and cisplatin showed promising activity as first-line therapy in patients with recurrent or metastatic nasopharyngeal carcinoma in a phase 1 trial. We therefore compared camrelizumab plus gemcitabine and cisplatin with placebo plus gemcitabine and cisplatin in a randomised phase 3 trial. In this randomised, double-blind, phase 3 trial done at 28 hospitals in China, patients were eligible if they were aged 18–75 years, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and had previously untreated recurrent or metastatic nasopharyngeal carcinoma. Patients were randomly assigned (1:1; using an interactive web-response system with a block size of four) to receive either camrelizumab (200 mg on day 1) or matching placebo intravenously, plus gemcitabine and cisplatin (gemcitabine 1000 mg/m2 on days 1 and 8; cisplatin 80 mg/m2 on day 1) intravenously every 3 weeks for four to six cycles, followed by maintenance therapy with camrelizumab or placebo, until radiographic progression, unacceptable toxicity, start of new anticancer treatment, investigator decision, or withdrawal of consent. Stratification factors used in randomisation were liver metastases, previous radical concurrent chemoradiotherapy, and ECOG performance status. The allocation sequence was generated by an independent randomisation group. The primary endpoint was progression-free survival per independent review committee. The significance threshold for independent review committee-assessed progression-free survival was p=0·0086 (one-sided) at the interim analysis. Efficacy and safety analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03707509, and is closed for enrolment but is ongoing. Between Nov 13, 2018, and Nov 29, 2019, 343 patients were screened and 263 were eligible and were randomly assigned to the camrelizumab group (n=134) or placebo group (n=129). At the prespecified interim analysis (June 15, 2020), independent review committee-assessed progression-free survival was significantly longer in the camrelizumab group (median 9·7 months [95% CI 8·3–11·4]) than in the placebo group (median 6·9 months [5·9–7·3]; hazard ratio 0·54 [95% CI 0·39–0·76]; one-sided p=0·0002). As of Dec 31, 2020, the most common grade 3 or worse adverse events of any cause were decreased white blood cell count (89 [66%] of 134 patients in the camrelizumab group vs 90 [70%] of 129 patients in the placebo group), decreased neutrophil count (86 [64%] vs 85 [66%]), anaemia (53 [40%] vs 57 [44%]), and decreased platelet count (53 [40%] vs 52 [40%]). Serious adverse events were reported in 59 (44%) of 134 patients in the camrelizumab group and 48 (37%) of 129 patients in the placebo group. Treatment-related deaths occurred in five (4%) patients in the camrelizumab group (two unknown cause of death, one multiple organ dysfunction syndrome, one pharyngeal haemorrhage, and one arrhythmia) and one (<1%) patient in the placebo group (unknown cause of death). Our findings suggest that camrelizumab plus gemcitabine and cisplatin could be a new standard of care for patients with recurrent or metastatic nasopharyngeal carcinoma in the first-line setting. Longer follow-up is needed to confirm this conclusion. Jiangsu Hengrui Pharmaceuticals (formerly Jiangsu Hengrui Medicine). For the Chinese translation of the abstract see Supplementary Materials section.

Background: With the update of equipment, the hospital base of this study began to adopt craniospinal irradiation (CSI) intensity-modulated radiotherapy (IMRT) in May 2018 to replace the traditional CSI conventional radiotherapy (CRT) technology. The purpose of this study was designed to compare the differences in acute hematological adverse reactions induced by CSI-IMRT and CSI-CRT. Methods: The clinical data and hematological data of 102 patients with central nervous system malignant tumors who underwent CSI treatment at the 900th Hospital of Joint Logistics Support Force of PLA from January 2008 to August 2022 were analyzed retrospectively. The patients included 63 men and 39 women, aged 3 to 56 years old. On the basis of the radiotherapy technique used, the patients were divided into the CSI-IMRT group (38 cases) and CSI-CRT group (64 cases). Acute hematological adverse reactions during radiotherapy were compared between the two groups according to the Common Terminology Criteria for Adverse Events version 4.0. The Mann-Whitney U test was used to compare the measurement data, and the χ2 test was used to compare the count data. Results: No significant difference was found between the CSI-IMRT group and the CSI-CRT group in terms of sex, histopathological type, tumor location, spinal cord invasion, surgery, and the Eastern Cooperative Oncology Group score (χ2 = 0.004 to 6.213; all P > .05). No significant difference was found in onset time of myelosuppression (11 days (interquartile range [IQR]: 7 to 14; minimum [min] to maximum [max]: 0 to 26) vs 8 days (IQR: 7 to 15; min to max: 3 to 29)) and nadir time of myelosuppression (21 days (IQR: 18 to 25; min to max: 12 to 35) vs 22 days (IQR: 15 to 25; min to max: 12 to 36)) between the CSI-IMRT group and the CSI-CRT group (Z = −0.856, −0.248; all P > .05). There were no significant differences in the incidence of decreased white blood cell counts (WBC), platelet counts, and hemoglobin concentration between the CSI-IMRT group and the CSI-CRT group, 86.8% (33/38) vs 78.1% (50/64), 57.9% (22/38) vs 42.2% (27/64), 57.9% (22/38) vs 53.1% (34/64); χ2 = 1.195, 2.357, 0.219; all P > .05. There were no significant differences in the incidence of decreased WBC, platelet counts, and hemoglobin concentration (severe myelosuppression) in grades III and IV, 23.7% (9/38) vs 21.9% (14/64), 7.9% (3/38) vs 3.1% (2/64), 5.3% (2/38) vs 9.4% (6/64); χ2 = 0.045, 1.164, 0.558; all P > .05. Conclusions: There was no significant difference in the incidence of myelosuppression and severe myelosuppression (grade III or above) induced by CSI-IMRT and CSI-CRT. CSI-IMRT is worthy of further clinical application.

Background: Patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) have poor prognosis after surgery. Neoadjuvant chemoimmunotherapy (nCIT) and neoadjuvant chemoradiotherapy (nCRT) may improve outcomes, but their long-term efficacy remains unclear. Methods: This multicenter study analyzed LA-ESCC patients from three Chinese hospitals (2015–2024) who received nCIT or nCRT followed by surgery. Primary endpoint was 3-year overall survival (OS); secondary endpoints included objective response rate (ORR), pathologic complete response (pCR), disease-free survival (DFS), and adverse events. Propensity score matching balanced baseline characteristics. Results: Among 225 patients (87 nCRT, 138 nCIT), matched cohorts (87 per group) showed that nCRT had higher ORR (85.06% vs. 45.98%), T/N downstaging rates (78.16% vs. 58.62%; 85.06% vs. 45.98%), and pCR (37.90% vs. 14.90%) (all p < 0.01). After median follow-up (nCIT: 44.5 months; nCRT: 35.1 months), nCIT improved 3-year OS (75.90% vs. 55.60%) and DFS (66.40% vs. 47.30%) (p < 0.05). Subgroup analysis favored nCRT in N+ or non-cT4 disease. Clinical N stage independently predicted survival. Conclusion: nCIT demonstrates superior survival benefits in LA-ESCC, while nCRT may be more effective for N+ or non-cT4 patients. Further randomized trials are warranted.

Background Esophageal squamous cell carcinoma (ESCC), the most common type of esophageal cancer, characterized by low five-year survival rate, and concurrent chemoradiotherapy (CCRT) has been proposed to treat ESCC, while potential biomarkers for prognostic monitoring after optimized CCRT remains unknown. Methods Serum samples from 45 patients with ESCC were collected and categorized into three groups: Control (pre-CCRT), CCRT (during CCRT), and CCRT-1 M (one-month post-CCRT). The therapeutic effect was evaluated using CT imaging and established evaluation criteria. Untargeted metabolomic analysis was performed on the serum samples to identify differential metabolites caused by CCRT treatment, assessing their potential for prognostic monitoring. Results CCRT had significant therapeutic efficacy in patients with ESCC, as indicated by CT imaging and RECIST 1.1 solid tumor evaluation criteria. Notably, several metabolic markers were identified through non-targeted metabolomic analysis, highlighting changes following CCRT treatment. These differential metabolites are involved in the dysregulation of phenylalanine, tyrosine, and tryptophan biosynthesis, as well as histidine, arginine, and proline metabolism, and glycine, serine, and threonine metabolism, suggesting a reduction in glucose metabolism in patients with ESCC after CCRT. Additionally, ROC analysis indicated that the AUC of these metabolites exceeded 0.661, underscoring their diagnostic value for assessing CCRT efficacy and their potential use in prognostic monitoring. Comparative metabolomic analysis identified L-phenylalanine and lysine as promising serum biomarkers for predicting therapeutic outcomes. Conclusions CCRT shows considerable therapeutic benefit in patients with ESCC, with observed reductions in glucose metabolism post-treatment. L-phenylalanine and lysine may serve as potential serum biomarkers to predict CCRT efficacy.

Neoadjuvant immunochemotherapy (nICT) improves outcomes in esophageal squamous cell carcinoma (ESCC); however, patient response heterogeneity limits its clinical benefit. The aim of this study was to investigate the predictive value of the systemic immune-inflammation index and prognostic nutritional index score (SII-PNI score), which is jointly constructed from the systemic immune-inflammation index (SII) and prognostic nutritional index (PNI), for pathological complete response (pCR) and survival outcomes. This retrospective study included patients with stage II to IV ESCC who received nICT therapy at Wuhan Union Hospital (WHUH), Fujian Cancer Hospital (FJCH), and 900th Hospital of the Joint Service Support Force of the People's Liberation Army of China (900th Hospital). The predictive performance of SII-PNI score was validated using receiver operating characteristic (ROC) curves. Multivariate logistic regression confirmed SII-PNI score as an independent predictor of pCR. Additionally, Cox regression model and Kaplan-Meier survival curves were employed to analyze disease-free Survival (DFS) and overall survival (OS). A total of 345 patients were included, stratified into 0-score (n = 70), 1-score (n = 149), and 2-score (n = 126) groups. The combined cohort (Combined from FJCH cohort, WHUH cohort, 900th Hospital cohort) area under the ROC curve (AUC) revealed that SII-PNI score (AUC = 0.803) outperformed SII (AUC = 0.679, DeLong's test  < 0.001) and PNI (AUC = 0.667, DeLong's test  < 0.001) in predicting pCR. Compared with 0-score patients, those with 1-score (odds ratio [OR] = 0.159, 95% confidence interval [CI]:0.080-0.319,  < 0.001) and 2-score (OR = 0.025, 95% CI:0.009-0.073,  < 0.001) had significantly lower pCR rates. The 2-score group showed had shorter of DFS (hazard ratio [HR] = 2.487, 95% CI:1.414-4.374,  = 0.002) and OS (HR = 4.473, 95% CI:2.138-9.357,  < 0.001) versus the 0-score group. This study demonstrated for the first time that the SII-PNI score can be used as an independent predictor of pCR in patients with ESCC treated with nICT and has prognostic stratification value. This suggests that it has the potential to be a pre-treatment assessment tool for evaluating treatment response and prognosis before nICT treatment.

This study elucidates the mechanisms underlying the positive effect of glyceryl monolaurate (GML) on fetal intrauterine development via maternal gut-microbiota modulating effects using a sow model. Addition of GML (1000 mg/kg) improved neonatal intestinal conditions (jejunal villus height, VH/CD ratio and tight junctions) and dorsal longissimus muscle (MyoD, MyoG and MSTN) development in the GML-treated group. Furthermore, GML improved maternal gut microbiota composition by enriching short-chain fatty acid (SCFA)-producing bacteria Lactobacillus and Akkermansia. Meanwhile, SCFA concentrations in sow feces and newborn plasma, as well as their receptors (GPR41/43) in intestine and muscle were upregulated with GML, corresponding with enhanced antioxidative and anti-inflammatory capacity. Further correlation analysis revealed Akkermansia and Lactobacillus positively correlated with SCFAs, antioxidative indicators, and anti-inflammatory capacity markers. Moreover, GML inhibited the activation of the MAPK/NF-κB inflammatory signaling pathway. In summary, GML enhanced fetal intrauterine development by modulating sow intestinal SCFA-producing bacteria.

Neoadjuvant chemotherapy followed by radical cystectomy is the standard of care for patients diagnosed with muscle-invasive bladder cancer (MIBC). However, urinary diversion following radical cystectomy significantly reduces patient quality of life. In addition, patients who significantly respond to neoadjuvant chemotherapy have a strong will to preserve the bladder. Bladder-sparing therapy has become a research focus worldwide. Although the bladder-sparing regimen, referred to as trimodality therapy (TMT), has been accepted, the efficacy of immunotherapy combined with chemotherapy for bladder preservation in patients with MIBC has not yet been published. We describe the case of a 50-year-old male presented intermittent macrohematuria and was diagnosed with bladder urothelial carcinoma by diagnostic transurethral resection of bladder tumor (TURBt) with clinical stage IIIA (cT3bN0M0). A complete response was achieved after four courses of neoadjuvant chemotherapy combined with pembrolizumab. Then, we performed a second TURBt plus randomized biopsy by cystoscopy. The pathology indicated no tumor in the bladder. Adjuvant chemoradiotherapy and immunotherapy were subsequently performed. Imaging examinations, cystoscopy and urine tumor DNA (utDNA) levels were used for surveillance after treatment. Finally, the patient achieved bladder preservation and had remained cancer-free for 19 months at the last follow-up on February 20, 2021. This is the first published case study to describe neoadjuvant chemotherapy plus pembrolizumab followed by concurrent chemoradiotherapy as a novel bladder-sparing regimen and successfully achieved a promising outcome.

Microalgae play an important role in the formation of biofloc. To demonstrate the feasibility of Chlorella pyrenoidosa in biofloc formation, an experiment was performed with a simple random design consisting of five inoculation levels (in triplicate) of C. pyrenoidosa (0, 1 × 108, 1 × 109, 5 × 109, and 1 × 1010 cells·L−1) in the biofloc system. All treatments kept a C:N ratio of approximately 15:1. This study observed the effects of different initial concentrations of C. pyrenoidosa on biofloc formation, water quality and bacterial community in biofloc systems. The results indicated that C. pyrenoidosa had the ability to enhance biofloc development, especially when the C. pyrenoidosa initial concentration reached 5~10 × 109 cells·L−1. Too high or too low a concentration of C. pyrenoidosa will adversely affect the formation of biofloc. The effect of C. pyrenoidosa addition on water quality (TAN, NO2−-N, and NO3−-N) was not significant in the final stage. The inoculation of C. pyrenoidosa decreased the species richness and diversity of the bacterial community but increased the domination of Proteobacteria and Bacteroidota in the biofloc system, especially the order of Rhizobiales. The addition of C. pyrenoidosa could maintain water quality by increasing the proportion of several denitrifying bacteria, including Flavobacterium, Chryseobacterium, Pseudomonas, Brevundimonas, Xanthobacter, etc. These above dominant denitrifying bacteria in the biofloc system could play a major role in reducing the concentration of NO2−-N and NO3−-N. So, we recommended the reasonable concentration is 5~10 × 109 cells·L−1 if C. pyrenoidosa is used to rapidly produce biofloc.

This study aims to investigate the impact of dietary supplementation with selenium yeast (SeY) and glycerol monolaurate (GML) on the transfer of antioxidative capacity between the mother and fetus during pregnancy and its underlying mechanisms. A total of 160 sows with similar body weight and parity of 3–6 parity sows were randomly and uniformly allocated to four groups (n = 40) as follows: CON group, SeY group, GML group, and SG (SeY + GML) group. Animal feeding started from the 85th day of gestation and continued to the day of delivery. The supplementation of SeY and GML resulted in increased placental weight and reduced lipopolysaccharide (LPS) levels in sow plasma, placental tissues, and piglet plasma. Furthermore, the redox balance and inflammatory markers exhibited significant improvements in the plasma of sows fed with either SeY or GML, as well as in their offspring. Moreover, the addition of SeY and GML activated the Nrf2 signaling pathway, while downregulating the expression of pro-inflammatory genes and proteins associated with inflammatory pathways (MAPK and NF-κB). Vascular angiogenesis and nutrient transportation (amino acids, fatty acids, and glucose) were upregulated, whereas apoptosis signaling pathways within the placenta were downregulated with the supplementation of SeY and GML. The integrity of the intestinal and placental barriers significantly improved, as indicated by the increased expression of ZO-1, occludin, and claudin-1, along with reduced levels of DLA and DAO with dietary treatment. Moreover, supplementation of SeY and GML increased the abundance of Christensenellaceae_R-7_group, Clostridium_sensus_stricto_1, and Bacteroidota, while decreasing levels of gut microbiota metabolites LPS and trimethylamine N-oxide. Correlation analysis demonstrated a significant negative relationship between plasma LPS levels and placental weight, oxidative stress, and inflammation. In summary, dietary supplementation of SeY and GML enhanced the transfer of antioxidative capacity between maternal-fetal during pregnancy via gut–placenta axis through modulating sow microbiota composition.