Peanut, a major economic and oil crop known for the high protein and oil content, is extensively cultivated in China. Peanut plants have the ability to form nodules with rhizobia, where the nitrogenase converts atmospheric nitrogen into ammonia nitrogen that can be utilized by the plants. Analysis of nodule fixation is of positive significance for avoiding overapplication of chemical fertilizer and developing sustainable agriculture. In this study, AhNIGT1.2, a member of the NIGT family predominantly expressed in peanut nodules, was identified by bioinformatics analysis. Subsequent spatiotemporal expression analysis revealed that AhNIGT1.2 was highly expressed in nodules and showed significant responses to high nitrogen, low nitrogen, high phosphorus, low phosphorus, and rhizobia treatments. Histochemical staining indicated that the gene was primarily expressed in developing nodules and at the connection region between mature nodules and peanut roots. The fusion protein AhNIGT1.2-GFP was located in the nucleus of tobacco epidermal cells. The AhNIGT1.2-OE significantly increased the number of peanut nodules, while AhNIGT1.2-RNAi reduced the number of nodules, which suggested a positive regulatory role of AhNIGT1.2 in peanut nodulation. The AhNIGT1.2-OE in roots down-regulated the expression levels of NRT1.2, NRT2.4, NLP1, and NLP7, which indicated that AhNIGT1.2 influenced peanut nodulation by modulating nitrate transport and the expression of NLP genes. The transcriptome analysis of AhNIGT1.2-OE and control roots revealed that overexpressing AhNIGT1.2 significantly enriched the differentially expressed genes associated with nitrate response, nodulation factor pathway, enzymes for triterpene biosynthesis, and carotenoid biosynthesis. These findings suggest that AhNIGT1.2 play a key role in peanut nodulation by regulating nitrate transport and response and other related pathways. This study gives insights into the molecular mechanisms of nitrogen and phosphorus in regulating legume nodulation and nitrogen fixation, and sheds light on the development of legume crops that can efficiently fix nitrogen in high nitrogen environments.
Arachis/physiology* ; Nitrates/metabolism* ; Plant Proteins/physiology* ; Transcription Factors/metabolism* ; Plant Root Nodulation/physiology* ; Gene Expression Regulation, Plant ; Root Nodules, Plant/metabolism* ; Nitrogen Fixation

Objective:To investigate the changing trends in cardiac function following xenogeneic heterotopic heart transplantation of multi-gene edited pig hearts and assess the impact of recipient immune responses on donor heart, laying experimental groundwork for the clinical application of gene editing technology.Methods:On December 16, 2023, xenogeneic heterotopic heart transplantation was performed between pigs and rhesus monkeys. Functional status of the graft under post-transplantation load conditions and recipient immune indicators were observed.Results:The recipient monkeys survived for 40 days with satisfactory functionality of both donor and recipient hearts, and no hyperacute or acute immune rejection reactions were observed.Conclusion:Multi-gene editing technology provides potential for xenotransplantation, yet further exploration is needed for its clinical application.

Objective To analyze the implementation effect of quality control on the homepage of inpatient medical re-cords based on the background of Disease Diagnosis Related Groups(DRG).Methods A retrospective study was conducted,including a total of 20,000 medical records from Dongguan People's Hospital from 2018 to 2022.Among them,10,000 medical records from January to December 2018,before the implementation of DRG-based quality control,were included as the control group;10,000 medical records from January to December 2022,after the implementation of DRG-based quality control,were in-cluded as the observation group.The implementation effect of quality control of hospital admission medical records among different groups based on DRG was explored.Results In the control group,there were 1,943 medical records with defects,accounting for 19.43％,which affected DRG grouping in 1,000 cases(51.47％)and did not affect DRG grouping in 943 cases(48.53％).In the observation group,there were 1,316 medical records with defects,accounting for 13.16％,among which 643 cases(48.86％)affected DRG grouping and 673 cases(51.14％)did not affect DRG grouping.The difference in the number of defective medical records between the groups was statistically significant(χ2=144.11,P<0.05).The missing rates of diagnos-tic and treatment information and cost information in the observation group were lower than those in the control group(P<0.05).The completeness and accuracy rates of diagnosis and surgical information in the observation group were higher than those in the control group(P<0.05).Conclusion The implementation of quality control of hospital admission medical records based on DRG can significantly improve the quality of medical records,increase the accuracy of diagnosis and surgical information in medi-cal records,and have higher comprehensive quality control value.It is recommended for clinical promotion and use.

Background: SM-like (LSM) genes a family of RNA-binding proteins, are involved in mRNA regulation and can function as oncogenes by altering mRNA stability. However, their roles in B-cell progression and tumorigenesis remain poorly understood. Methods: We analyzed gene expression profiles and overall survival data of 123 patients with mantle cell lymphoma (MCL). The LSM index was developed to assess its potential as a prognostic marker of MCL survival. Results: Five of the eight LSM genes were identified as potential prognostic markers for survival in MCL, with particular emphasis on the LSM.index. The expression levels of these LSM genes demonstrated their potential utility as classifiers of MCL. The LSM.index-high group exhibited both poorer survival rates and lower RNA levels than did the overall transcript profile. Notably, LSM1 and LSM8 were overexpressed in the LSM.index-high group, with LSM1 showing 2.5-fold increase (p < 0.001) and LSM8 depicting 1.8-fold increase (p < 0.01) than those in the LSM.index-low group.Furthermore, elevated LSM gene expression was associated with increased cell division and RNA splicing pathway activity. Conclusions The LSM.index demonstrates potential as a prognostic marker for survival in patients with MCL. Elevated expression of LSM genes, particularly LSM1 and LSM8, may be linked to poor survival outcomes through their involvement in cell division and RNA splicing pathways. These findings suggest that LSM genes may contribute to the aggressive behavior of MCL and represent potential targets for therapeutic interventions.

Background: SM-like (LSM) genes a family of RNA-binding proteins, are involved in mRNA regulation and can function as oncogenes by altering mRNA stability. However, their roles in B-cell progression and tumorigenesis remain poorly understood. Methods: We analyzed gene expression profiles and overall survival data of 123 patients with mantle cell lymphoma (MCL). The LSM index was developed to assess its potential as a prognostic marker of MCL survival. Results: Five of the eight LSM genes were identified as potential prognostic markers for survival in MCL, with particular emphasis on the LSM.index. The expression levels of these LSM genes demonstrated their potential utility as classifiers of MCL. The LSM.index-high group exhibited both poorer survival rates and lower RNA levels than did the overall transcript profile. Notably, LSM1 and LSM8 were overexpressed in the LSM.index-high group, with LSM1 showing 2.5-fold increase (p < 0.001) and LSM8 depicting 1.8-fold increase (p < 0.01) than those in the LSM.index-low group.Furthermore, elevated LSM gene expression was associated with increased cell division and RNA splicing pathway activity. Conclusions The LSM.index demonstrates potential as a prognostic marker for survival in patients with MCL. Elevated expression of LSM genes, particularly LSM1 and LSM8, may be linked to poor survival outcomes through their involvement in cell division and RNA splicing pathways. These findings suggest that LSM genes may contribute to the aggressive behavior of MCL and represent potential targets for therapeutic interventions.

Background: SM-like (LSM) genes a family of RNA-binding proteins, are involved in mRNA regulation and can function as oncogenes by altering mRNA stability. However, their roles in B-cell progression and tumorigenesis remain poorly understood. Methods: We analyzed gene expression profiles and overall survival data of 123 patients with mantle cell lymphoma (MCL). The LSM index was developed to assess its potential as a prognostic marker of MCL survival. Results: Five of the eight LSM genes were identified as potential prognostic markers for survival in MCL, with particular emphasis on the LSM.index. The expression levels of these LSM genes demonstrated their potential utility as classifiers of MCL. The LSM.index-high group exhibited both poorer survival rates and lower RNA levels than did the overall transcript profile. Notably, LSM1 and LSM8 were overexpressed in the LSM.index-high group, with LSM1 showing 2.5-fold increase (p < 0.001) and LSM8 depicting 1.8-fold increase (p < 0.01) than those in the LSM.index-low group.Furthermore, elevated LSM gene expression was associated with increased cell division and RNA splicing pathway activity. Conclusions The LSM.index demonstrates potential as a prognostic marker for survival in patients with MCL. Elevated expression of LSM genes, particularly LSM1 and LSM8, may be linked to poor survival outcomes through their involvement in cell division and RNA splicing pathways. These findings suggest that LSM genes may contribute to the aggressive behavior of MCL and represent potential targets for therapeutic interventions.

Purpose: We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations. Materials and Methods: This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint. Results: The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment. Conclusion EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

Objective:To establish and validate a reliable and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection of 12 ceramides in human plasma.Methods:From October 2021 to October 2022, 438 apparently healthy individuals were enrolled in the Affiliated Hospitals of Zunyi Medical University for reference intervals of 12 ceramides in this population. Plasma samples were collected, and separated using the ACQUITY UPLC BEH C18 (2.1×50 mm, 1.7 μm) column, deuterated isotopes were used as internal standards. The mobile phase is water (containing 0.1% formic acid) and isopropanol: acetonitrile (1∶1, v/v, containing 0.1% formic acid) at a flow rate of 0.4 ml/min with gradient elution. The detection method was established using the Qlife Lab 9000 Plus triple quadrupole mass spectrometer. The performance of the method was evaluated in terms of linearity, the lower limit of quantification, precision, recovery, and stability.Results:The method passed the performance evaluation in terms of linearity, the lower limit of quantification, recovery, precision, and stability. The intra-and inter-batch precision of the 12 ceramides ranged from 1.3% to 14.3%, the correctness was verified by spiked recovery experiments, and the recoveries ranged from 91.9% to 111.0%. The lower limit of quantification ranged from 0.001 to 0.100 μmol/L. Standard curve showed good linearity (correlation coefficient r>0.990). Stability tests showed that the 12 ceramides were stable in the biological matrix and after processing under different conditions for a specified period of time. The corresponding biological reference intervals were established for each of the 12 ceramides: 0.103-0.326 μmol/L for Cer(d18∶1/16∶0), 0.018-0.098 μmol/L for Cer(d18∶1/18∶0), 0.933-3.919 μmol/L for Cer(d18∶1/24∶0), 0.243-1.072 μmol/L for Cer(d18∶1/24∶1), 0.001-0.007 μmol/L for Cer(d18∶1/14∶0), 0.022-0.095 μmol/L for Cer(d18∶1/20∶0), 0.185-0.835 μmol/L for Cer(d18∶1/22∶0), 0.003-0.022 μmol/L for Cer(d18∶0/16∶0), 0.001-0.016 μmol/L for Cer(d18∶0/18∶0), 0.017-0.156 μmol/L for Cer(d18∶0/24∶0), 0.008-0.074 μmol/L for Cer(d18∶0/24∶1), and 0.106-0.721 μmol/L for LacCer(d18∶1/24∶1). Conclusion:Our study shows that the newly established LC-MS/MS method for the determination of 12 ceramides in human plasma is reliable, and suitable for clinical application.

Objective:To explore the TCM syndromes and risk factors of patients with anxiety and/or depression after coronary revascularization through real-world data mining based on the national pilot project of Chinese and Western medicine clinical collaboration for major difficult diseases; To provide clinical evidence and guide practice for the diagnosis and treatment of bicardiac diseases after coronary revascularization.Methods:A retrospective multi-center clinical study was conducted. From September 2018 to December 2019, 577 patients who underwent successful percutaneous coronary intervention in the Department of Cardiovascular Medicine of Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Department of Cardiovascular Medicine of the People's Hospital of Liaoning Province were enrolled using the collaborative platform system of TCM and Western Medicine Diagnosis and follow-up for coronary disease. Clinical data database was established. Baseline data, TCM syndrome types and elements, coronary angiography and stent implantation status, relevant disease history, Hamilton Anxiety and Depression Scale, etc. were collected. A combination of postoperative phone calls and outpatient visits was performed, with follow-up every 3 months for a total of 1 year. The TCM treatment patterns and risk factors of patients with anxiety and depression after coronary artery revascularization surgery were analyzed and explored.Results:A total of 577 patients were enrolled and 561 patients were followed up. Age distribution: The age of males and females undergoing coronary revascularization due to ACS was (61.80±11.00) years and (68.37±10.13) years, with no statistical significance between groups ( P>0.05), but the age of onset in males tended to be earlier than in females. The distribution pattern of TCM syndrome elements showed that the most deficiency syndrome elements were qi deficiency (61.75%, 176/285), followed by yin deficiency (28.77%, 82/285). The most common excessive symptom was blood stasis (39.13%, 108/276), and the other syndromes were phlegm turbidity (36.23%, 100/276) and qi depression (20.29%, 56/276), etc. The distribution of TCM syndrome types was as follows: in the population with anxiety and depression state of coronary revascularization, the TCM syndrome types with frequency higher than 10% were successively phlegm and blood stasis with depression syndrome, qi deficiency and blood stasis syndrome, heart, gallbladder and qi deficiency and qi-yin deficiency with blood stasis syndrome. Among the people without anxiety and depression, the TCM syndromes with a frequency higher than 10% were heart blood stasis syndrome and qi deficiency and blood stasis syndrome, with statistical significance ( χ2=12.07, P<0.01). Correlation analysis showed that the number of stents, and LDL-C were positive correlated with anxiety and depression( r values were 0.107, 0.118,respectively, P<0.05), and the uric acid was negative correlation ( r=-0.127, P=0.011). Multivariate Cox proportional hazards regression showed the age [ RR (95% CI)=1.052 (1.012-1.094), P=0.010] and diabetes mellitus [ RR (95% CI)=4.561 (1.028-20.238), P=0.046] at the sixth month of treatment. Conclusions:The age of acute coronary syndrome and coronary revascularization is mainly concentrated in patients aged 60-70 years, and male patients tend to have earlier onset than female patients, and the risk of coronary heart disease is relatively high. Qi-deficiency syndrome accounts for the highest proportion, and the most excessive syndrome is blood stasis syndrome. The TCM syndromes with high frequency of anxiety and depression are phlegm and blood stasis with depression syndrome and qi-yin deficiency with blood stasis syndrome. The number of stents implanted and low density lipoprotein cholesterol are positively correlated with postoperative anxiety and depression. Age and diabetes history are independent risk factors for end-point events at about 6 months after treatment.

Objective:Four cases with NLRP3-related autoinflammatory diseases were reported to summarize the clinical characteristics, genotype, and treatment responses of the disease, and to improve clinical pediatricians' understanding of the disease.Methods:A retrospective analysis was performed on 4 cases with NLRP3-related autoinflammatory diseases diagnosed in Children's Hospital of Anhui Province in 2016—2021, and the clinical features and treatment progress of NLRP3-related autoinflammatory diseases were retrospectively analyzed based on the clinical features, gene reports, and literature review.Results:① All 4 cases were male. Cases 1, 2, and 3 had the disease onset after birth, and case 4 had the disease onset 6 months after birth. All showed periodic fever, repeated urticaria-like rash, protruding forehead, and saddle nose. White blood cells count, erythrocyte sedimentation rate, and C-reactive protein were increased during the attack period, and those in the interval period were normal, and antibiotic treatment was ineffective. ② The genetic test of all these 4 children showed NLRP3 mutation. Children 1, 2, and 3 were heterozygous mutations, and their parents were wild-type. The mutation was located at chromosome Chr1: 247587658, exon c913 (exon3). G>A, the 305th aspartic acid (Asp) of the protein was changed to asparagine (Asn) in child 1. The mutation was located at the chromosomal Chr1: 247588072, the nucleic acid was changed to c1327(exon3)T>C, and the amino acid was changed to p.Y443H in cases 2 and 3. Somatic heterozygous mutation was found in case 4, and the child's parents were wild-type. In this case, the mutation was located at chromosomal Chr1: 247587658, exon3 G>A, and the 305th Asp of the protein was changed to Asn. ③Children in cases 1, 2, and 3 were treated with glucocorticoids and non-steroidal anti-inflammatory drugs at the initial stage, but the effects were limited. After receiving IL-1 antagonist treatment fever, skin rash, joint swelling and pain disappeared, and the inflammatory indexes were returned to normal. The child 4 received non-steroidal anti-inflammatory drugs and methotrexate, but he failed to respond to the treatment. Treatment with tocilizumab was not effective, however, fever, skin rash, or joint pain disappeared after treated with Khanna.Conclusion:①NLRP3-related autoinflammatory diseases can cause periodic fever, urticaria, joint involvement, and severe involvement of the central nervous system and organ amyloidosis. Which are early misdiagnosis is prone to systemic juvenile idiopathic arthritis. ②The disease was an inflammatory disease mediated by interleukin-1. At present, non-steroidal anti-inflammatory drug, glucocorticoid and chronic anti-rheumatic drugs have limited effects. IL-1 antagonists are effective and safe in the treatment of the disease.