Biomarkers to predict efficacy of immune checkpoint inhibitors in colorectal cancer patients: a systematic review and meta-analysis.

Immune checkpoint inhibitors (ICIs) are approved to treat colorectal cancer (CRC) with mismatch-repair gene deficiency, but the response rate remains low. Value of current biomarkers to predict CRC patients' response to ICIs is unclear due to heterogeneous study designs and small sample sizes. Here, we aim to assess and quantify the magnitude of multiple biomarkers for predicting the efficacy of ICIs in CRC patients. We systematically searched MEDLINE, Embase, the Cochrane Library, and Web of Science databases (to June 2023) for clinical studies examining biomarkers for efficacy of ICIs in CRC patients. Random-effect models were performed for meta-analysis. We pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) for biomarkers predicting response rate and survival. 36 studies with 1867 patients were included in systematic review. We found that a lower pre-treatment blood neutrophil-to-lymphocyte ratio (n=4, HR 0.37, 95%CI 0.21-0.67) predicts good prognosis, higher tumor mutation burden (n=10, OR 4.83, 95%CI 2.16-10.78) predicts response to ICIs, and liver metastasis (n=16, OR 0.32, 95%CI 0.16-0.63) indicates resistance to ICIs, especially when combined with VEGFR inhibitors. But the predictive value of tumor PD-L1 expression (n=9, OR 1.01, 95%CI 0.48-2.14) was insignificant in CRC. Blood neutrophil-to-lymphocyte ratio, tumor mutation burden, and liver metastasis, but not tumor PD-L1 expression, function as significant biomarkers to predict efficacy of ICIs in CRC patients. These findings help stratify CRC patients suitable for ICI treatments, improving efficacy of immunotherapy through precise patient management. (PROSPERO, CRD42022346716).

Fine mapping and candidate gene analysis of qSB12YSB, a gene conferring major quantitative resistance to rice sheath blight.

KEY MESSAGE: qSB12YSB, a major quantitative sheath blight resistance gene originated from rice variety YSBR1 with good breeding potential, was mapped to a 289-Kb region on chromosome 12. Sheath blight (ShB), caused by Rhizoctonia solani kühn, is one of the most serious global rice diseases. Rice resistance to ShB is a typical of quantitative trait controlled by multiple quantitative trait loci (QTLs). Many QTLs for ShB resistance have been reported while only few of them were fine-mapped. In this study, we identified a QTL on chromosome 12, in which the qSB12YSB resistant allele shows significant ShB resistance, by using 150 BC4 backcross inbred lines employing the resistant rice variety YSBR1 as the donor and the susceptible variety Lemont (LE) as the recurrent parent. We further fine-mapped qSB12YSB to a 289-kb region by generating 34 chromosomal segment substitution lines and identified a total of 18 annotated genes as the most likely candidates for qSB12YSB after analyzing resequencing and transcriptomic data. KEGG analysis suggested that qSB12YSB might activate secondary metabolites biosynthesis and ROS scavenging system to improve ShB resistance. qSB12YSB conferred significantly stable resistance in three commercial rice cultivars (NJ9108, NJ5055 and NJ44) in field trials when introduced through marker assisted selection. Under severe ShB disease conditions, qSB12YSB significantly reduced yield losses by up to 13.5% in the LE background, indicating its great breeding potential. Our results will accelerate the isolation of qSB12YSB and its utilization in rice breeding programs against ShB.

Ultrasound assessment of gastric content in patients undergoing laparoscopic cholecystectomy after preoperative oral carbohydrates: a prospective, randomized controlled, double-blind study.

Background: To evaluate the gastric volume and nature after drinking preoperative oral carbohydrates in patients undergoing laparoscopic cholecystectomy via ultrasonography. Methods: One hundred patients who had been scheduled for elective laparoscopic cholecystectomy were enrolled and randomized into the traditional fasting group (Control group, n = 50) and the carbohydrate group (CHO group, n = 50). Patients in the Control group fasted solids and drink from midnight, the day before surgery. Patients in the CHO group drank 800 ml and 400 ml of oral carbohydrates 11 and 3 h before surgery, respectively. At 2 h after oral carbohydrates (T1), all patients underwent an ultrasound examination of residual gastric contents; if the patients had a full stomach, the assessment was performed again 1 h later (T2). A stomach containing solid contents or >1.5 ml/kg of liquid was considered "full". The primary outcome was full stomach incidences at the above time points. The secondary outcomes included gastric antral CSA in the right lateral decubitus (RLD) and semi-sitting positions, as well as gastric volume (GV), GV per weight (GV/kg), and Perla's grade at T1. Results: Compared with the Control group, the incidence of entire stomach was significantly high in the CHO group 2 h after oral carbohydrates. At the T1 time point, 6 patients (13.3%) in the Control group and 14 patients (30.4%) in the CHO group presented with a full stomach [95% confidence interval (CI), (0.96-5.41), P = 0.049]. At T2, 3 patients (6.7%) in the Control group and 4 patients (8.7%) in the CHO group had a full stomach, with no marked differences between the two groups [95% CI, (0.31-5.50), P = 0.716]. Compared with the Control group, CSA in the semi-sitting and RLD positions, GV and GV/W were significantly high in the CHO group at T1 (P < 0.05). The median (interquartile range) of the Perlas grade was 1 (0-1) in the Control group and 1(1-1.25) in the CHO group (P = 0.004). Conclusion: Cholecystectomy patients experience a 2 h delay in gastric emptying after receiving preoperative carbohydrates. In LC patients, the fasting window for oral carbohydrates before surgery should be adequately prolonged. Clinical Trail registration: Chinese Clinical Trail Registry, No: ChiCTR2200055245.

Identification of Elite R-Gene Combinations against Blast Disease in Geng Rice Varieties.

Rice blast, caused by the Magnaporthe oryzae fungus, is one of the most devastating rice diseases worldwide. Developing resistant varieties by pyramiding different blast resistance (R) genes is an effective approach to control the disease. However, due to complex interactions among R genes and crop genetic backgrounds, different R-gene combinations may have varying effects on resistance. Here, we report the identification of two core R-gene combinations that will benefit the improvement of Geng (Japonica) rice blast resistance. We first evaluated 68 Geng rice cultivars at seedling stage by challenging with 58 M. oryzae isolates. To evaluate panicle blast resistance, we inoculated 190 Geng rice cultivars at boosting stage with five groups of mixed conidial suspensions (MCSs), with each containing 5-6 isolates. More than 60% cultivars displayed moderate or lower levels of susceptibility to panicle blast against the five MCSs. Most cultivars contained two to six R genes detected by the functional markers corresponding to 18 known R genes. Through multinomial logistics regression analysis, we found that Pi-zt, Pita, Pi3/5/I, and Pikh loci contributed significantly to seedling blast resistance, and Pita, Pi3/5/i, Pia, and Pit contributed significantly to panicle blast resistance. For gene combinations, Pita+Pi3/5/i and Pita+Pia yielded more stable pyramiding effects on panicle blast resistance against all five MCSs and were designated as core R-gene combinations. Up to 51.6% Geng cultivars in the Jiangsu area contained Pita, but less than 30% harbored either Pia or Pi3/5/i, leading to less cultivars containing Pita+Pia (15.8%) or Pita+Pi3/5/i (5.8%). Only a few varieties simultaneously contained Pia and Pi3/5/i, implying the opportunity to use hybrid breeding procedures to efficiently generate varieties with either Pita+Pia or Pita+Pi3/5/i. This study provides valuable information for breeders to develop Geng rice cultivars with high resistance to blast, especially panicle blast.

Development of Rice Variety With Durable and Broad-Spectrum Resistance to Blast Disease Through Marker-Assisted Introduction of Pigm Gene.

Rice blast, caused by Magnaporthe oryzae (M. oryzae), is one of the most destructive diseases threatening rice production worldwide. Development of resistant cultivars using broad-spectrum resistance (R) genes with high breeding value is the most effective and economical approach to control this disease. In this study, the breeding potential of Pigm gene in geng/japonica rice breeding practice in Jiangsu province was comprehensively evaluated. Through backcross and marker-assisted selection (MAS), Pigm was introduced into two geng rice cultivars (Wuyungeng 32/WYG32 and Huageng 8/HG8). In each genetic background, five advanced backcross lines with Pigm (ABLs) and the same genotypes as the respective recurrent parent in the other 13 known R gene loci were developed. Compared with the corresponding recurrent parent, all these ABLs exhibited stronger resistance in seedling inoculation assay using 184 isolates collected from rice growing regions of the lower region of the Yangtze River. With respect to panicle blast resistance, all ABLs reached a high resistance level to blast disease in tests conducted in three consecutive years with the inoculation of seven mixed conidial suspensions collected from different regions of Jiangsu province. In natural field nursery assays, the ABLs showed significantly higher resistance than the recurrent parents. No common change on importantly morphological traits and yield-associated components was found among the ABLs, demonstrating the introduction of Pigm had no tightly linked undesirable effect on rice economically important traits and its associated grain weight reduction effect could be probably offset by others grain weight genes or at least in the background of the aforementioned two varieties. Notably, one rice line with Pigm, designated as Yangnonggeng 3091, had been authorized as a new variety in Jiangsu province in 2021, showing excellent performance on both grain yield and quality, as well as the blast resistance. Together, these results suggest that the Pigm gene has a high breeding value in developing rice varieties with durable and broad-spectrum resistance to blast disease.