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Hepatic venous pressure gradient (HVPG) is the gold standard for evaluating clinically significant portal hypertension (CSPH). However, reliable noninvasive methods are limited. Our study aims to investigate the diagnostic value of serum Golgi protein 73 (GP73) for CSPH in patients with compensated cirrhosis. The study enrolled 262 consecutive patients with compensated cirrhosis from three centers in China from February 2021 to September 2023, who underwent both serum GP73 tests and HVPG measurements. CSPH was defined as HVPG ≥ 10 mmHg. Diagnostic accuracy was evaluated using the areas under the receiver operating characteristic curve (AUC). The prevalence of CSPH was 56.9% (n = 149). There were significant differences between the CSPH and non‐CSPH groups in the median serum GP73 level (126.8 vs. 73.1 ng/mL, p < 0.001). GP73 level showed a significant positive linear correlation with HVPG (r = 0.459, p < 0.001). The AUC for the diagnosis of CSPH using serum GP73 alone was 0.75 (95% confidence interval [CI] 0.68–0.81). Multivariate logistic regression analysis determined that the levels of GP73, platelets and international normalized ratio were independently associated with CSPH. The combination of these three markers was termed "IP73" score with an AUC value of 0.85 (95% CI 0.80–0.89) for CSPH. Using 0 as a cut‐off value, the specificity and sensitivity of IP73 score were 77.9% and 81.9%, respectively. The IP73 score offers a novel, simple and noninvasive method of assessing CSPH in patients with compensated cirrhosis. A cut‐off value of the IP73 score at 0 can distinguish patients with or without CSPH. [ABSTRACT FROM AUTHOR]

Aim: A third‐line chemotherapy regimen for metastatic colorectal cancer (mCRC) is not available in China. Studies have shown that raltitrexed or S‐1 has no complete cross‐resistance with fluorouracil (5‐FU). In this phase II study, we prospectively analyzed the efficacy and safety of raltitrexed combined with S‐1 (RS regimen) in the treatment of mCRC after the failure of conventional chemotherapy. Methods: A total of 105 patients with mCRC with progression following treatment with 5‐FU, oxaliplatin, and irinotecan were enrolled between November 2015 and May 2019. Patients received intravenous infusion of raltitrexed (3 mg/m2 from day 1 every 3 weeks) and oral S‐1 (80‐120 mg for 14 days every 3 weeks). Tumor evaluations were performed every two cycles according to the RECIST 1.1 guidelines. Results: In the intention‐to‐treat patients, the objective response and disease control rates were 7.62% and 48.57%, respectively. The median progression‐free survival and median overall survival were 2.5 and 8.0 months, respectively. Common adverse events included neutropenia, anemia, thrombocytopenia, and nausea, while neutropenia, anemia, thrombocytopenia nausea, diarrhea, skin eruption, and oral ulceration had grade 3 or higher adverse events. Subgroup analysis revealed that primary site or gene mutation status had little influence on the RS regimen efficacy, while the baseline albumin level, 5‐FU administration in second‐line therapy, and number of previous treatment regimens affected the efficacy. Conclusion: The RS regimen demonstrated favorable effects in patients with mCRC following failure of standard chemotherapy, and could be a new choice for third‐line treatment, and must be verified in future randomized clinical trials (Clinical trial: NCT02618356). [ABSTRACT FROM AUTHOR]

The hereditary basis and identification of novel genes of heading date have significant implications for japonica rice improvement in northeast China, especially in Heilongjiang province. A re‐sequenced recombinant inbred line (RIL) population derived from the cross between Lijiangxintuanheigu (LTH) and Shennong 265 (SN265) was used to detect the genetic basis for the RIL in 2017 and 2018. Fourteen heading date quantitative trait loci (QTLs), including nine in 2017 and thirteen in 2018, were detected with a linkage map containing 2,818 bin markers. They were distributed on chromosomes 3, 4, 6 and 9–11 with 9.34%–25.26% phenotypic variations. The QTLs qHD3a, qHD4a, qHD4b, qHD4c, qHD9b, qHD10, qHD11c and qHD11d were identified in both years. The qTRS1, qTRS3a (qHD3a), qTRS3b (qHD3b) and qTRS9 (qHD9a) alleles from LTH and the qTRS4 allele from SN265 were identified by controlling the temperature responsiveness in the RIL population. The explained phenotypic variation in these five QTLs varied from 14.52% to 26.31%. In order to accurately determine the difference in heading date under different temperature conditions, the RILs and two parents were grown in a phytotron. Four QTLs controlling temperature responsiveness were identified on chromosomes 3, 6 and 9, including qTRS3a (qHD3a), qTRS3b (qHD3b), qTRS6 and qTRS9 (qHD9a). In a different environment, qTRS3a (qHD3a), qTRS3b (qHD3b) and qTRS9 (qHD9a) were detected. A comparison of chromosomal locations between the QTLs detected in this study and heading date genes previously cloned indicated that DTH3, Hd16, RFL, HAF1, Ehd2 and RBS1 might be candidate genes for them. The four major heading date genes (Hd1, Ghd7, Ghd7.1 and Ghd8) affecting ecogeographical adaptation were sequenced between SN265 and LTH. SN265 carried a functional Hd1 haplotype, a weak functional Ghd7 haplotype, a weak functional Ghd7.1 haplotype and a weak functional Ghd8 haplotype. LTH also carried functional Hd1 haplotype, a weak functional Ghd7 haplotype, a non‐functional Ghd7.1 haplotype and a non‐functional Ghd8 haplotype. The combinations of the Hd1, Ghd7, Ghd7.1 and Ghd8 alleles in SN265 and LTH largely defined their short heading date under long‐day conditions. The selection of heading date gene combinations with functional Hd1 alleles and non‐functional alleles or weak functional alleles of Ghd7, Ghd7.1 and Ghd8 would be an effective way to improve japonica rice with proper heading days in Northeast China. The novel QTLs detected in this study could also become a valuable source for designing the appropriate heading date in Northeast China japonica rice. [ABSTRACT FROM AUTHOR]