Rice (Oryza sativa L.) is an important food crop. The appearance of lesion mimics in rice leads to phytohormone disorders, which affects rice adaptation to environmental stresses and ultimately reduces the yield and quality. To explore whether the changes in the adaptability of rice lesion-mimic mutants to stressful environments are caused by the disorder of phytohormone metabolism in plants. In this study, we screened an ethyl methane sulfonate-treated population of the japonica cultivar 'Taipei 309' for a mutant with rust-like spots on leaves at the early tillering stage and brown-red spots at maturity and named it rsl1 (rust spotted leaf 1). Compared with the wild type, rsl1 showed decreases in plant height, panicle length, primary branch number, secondary branch number, filled grains per panicle, seed-setting rate, and 1 000-grain weight, and an increase in number of effective panicles. Genetic analysis indicated that rsl1 was controlled by a single recessive nuclear gene. RSL1 was localized between two molecular markers, B7-7 and B7-9, on rice chromosome 7 by map-based cloning. PCR sequencing of the annotated genes in this interval revealed a mutation of C1683A on the eighth exon of SPL5 (LOC_Os07g10390) in rsl1, which resulted in premature termination of protein translation. Exogenous phytohormone treatments showed that rsl1 was less sensitive to salicylic acid (SA), abscisic acid (ABA), and indo-3-acetic acid (IAA) and more sensitive to methyl jasmonate (MeJA) and gibberellin acid (GA) than the wild type. In addition, the survival rate of rsl1 was lower than that of the wild type under salt, alkali, drought, and high temperature stresses, and it was higher than that of the wild type under cold stress. Quantitative real-time polymerase chain reaction (qRT-PCR) results showed that RSL1 was involved in the regulation of ABA, SA, MeJA, IAA, and GA-related genes under abiotic stresses. The present study showed that the RSL1 mutation led to the appearance of lesion mimics and affected the growth, development, and stress resistance of rsl1 under abiotic stresses. The study of the functional mechanism of this gene can provide theoretical guidance for the research on rice stress resistance.
Oryza/microbiology* ; Stress, Physiological/genetics* ; Plant Diseases/genetics* ; Cloning, Molecular ; Chromosome Mapping ; Plant Growth Regulators/metabolism* ; Plant Proteins/genetics* ; Mutation ; Cyclopentanes ; Genes, Plant ; Plant Leaves/genetics* ; Oxylipins

Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg⁻¹ ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg⁻¹; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg⁻¹) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg⁻¹ and 21.90 mg·kg⁻¹, and those of male mice were calculated to be 58.62 mg·kg⁻¹ and 54.31 mg·kg⁻¹, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg⁻¹ and 11.99 mg·kg⁻¹ for female mice, and 16.28 mg·kg⁻¹ and 10.47 mg·kg⁻¹ for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg⁻¹ and 19.92 mg·kg⁻¹ for female mice, and 24.74 mg·kg⁻¹ and 14.08 mg·kg⁻¹ for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg⁻¹, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.

"Reinforcing earth for generating metal" is based on the treatment principle of the five-element theory of traditional Chinese medicine （TCM）， which states that "reinforcing mother viscera for treating deficiency of child viscera". Based on the principle of inter-generating relationship in the five elements that earth generates metal， by strengthening the functions of the internal organs belonging to "earth" （spleen and stomach） to indirectly nourish the internal organs belonging to "metal" （lungs and large intestine）. Using reinforcing earth for generating metal in the treatment of lung cancer， according to the principle of "reinforcing mother viscera for treating deficiency of child viscera"， by strengthening the function of "earth" viscera， the treatment effect of "metal" viscera can be achieved. The metabolic disorder， inflammatory response， and immune regulation caused by the changes in the composition and structure of intestinal microbiota are involved in the occurrence and development of lung cancer， which is consistent with the theory of “the external and internal relationship between the lung and the large intestine” in TCM. From the perspective of intestinal microbiota microecology， the paper discusses the pathogenesis of "earth disease leads to metal disorders" that the gut microbiota dysbiosis causes lung cancer and the treatment method of "reinforcing earth for generating metal" by regulating the microecological balance of gut microbiota in lung cancer， suggesting the great significance of "reinforcing earth for generating metal" therapy aiming at microecological balance of gut microbiota in the treatment of lung cancer， in order to provide a different perspective for the treatment of lung cancer with TCM.

Objective:To analyze the prenatal characteristics and pregnancy outcomes of fetuses with 17q12 microdeletion or microduplication.Methods:From January 2018 to December 2022, 14 fetuses diagnosed with 17q12 microdeletion and three with 17q12 microduplication by chromosomal microarray analysis folloning invasive prenatal diagnostic techniques at Nanjing Maternity and Child Health Care Hospital were retrospectively enrolled in this study. Relevant articles up to February 1, 2023, were retrieved from PubMed, Embase, China National Knowledge Infrastructure, Wanfang database, and Yiigle with the terms "17q12 microdeletion", "17q12 microduplication", "prenatal diagnosis", and "pregnancy outcome". Eighty-four 17q12 microdeletion cases and fourteen 17q12 microduplication cases were retrieved. Prenatal ultrasound features and pregnancy outcomes of those fetuses were analyzed and summarized.Results:In this study, ninety-eight 17q12 microdeletion cases and seventeen 17q12 microduplication cases were analyzed. (1) 17q12 microdeletion: The prenatal ultrasound showed all the 17q12 microdeletion cases had renal abnormalities (100.0%, 98/98), and renal hyperechogenicity was detected in 81.6% (80/98) of them; pedigree analysis suggested that 74.2% (49/66) mutations were de novo; 64.1% (41/64) of pregnant women chose to terminate the pregnancy and 35.9%(23/64) chose to continue pregnancy; eight out of 12 live births who were followed up had different degrees of abnormalities and four were normal during the follow-up period. (2) 17q12 microduplication: Among the 17 fetuses, 10 had upper gastrointestinal obstruction; pedigree analysis suggested that four were de novo mutations (4/13); nine out of 14 pregnant women with reported pregnancy outcomes chose to terminate the pregnancy, and five continued the pregnancy to delivery; follow up of the live births found that four neonates were normal and one had a good prognosis after surgery. Conclusions:Fetuses with 17q12 microdeletion often show renal hyperechogenicity in ultrasound images, and most mutations were de novo with poor prognosis. 17q12 microduplication in fetuses is often characterized by upper gastrointestinal obstruction, and most inherited from their parents.

Objective To construct and identify the induced pluripotent stem cells(iPSCs)derived from peripheral blood mononuclear cells(PBMCs)of a patient with facioscapulohumeral muscular dystrophy(FSHD),initially explore their differentiation ability into skeletal muscle cells,and evaluate the feasibility of using this cell model for disease mechanism research.Methods The PBMCs from one FSHD patient were collected and transfected with Sendai virus containing four reprogramming transcription factors,including OCT4,SOX2,KLF4 and c-MYC,so as to obtain the iPSCs from the FSHD patient.Then,the iPSCs were induced to differentiate into skeletal muscle cells.The characteristics of the iPSCs and skeletal muscle cells were evaluated by the optical genome mapping technolo-gy,karyotyping analysis,immunofluorescence staining,and real-time fluorescence quantitative PCR.Results The iPSCs from the FSHD patient were successfully obtained,which could express the markers of iPSCs.The karyotype and D4Z4 repeat unit of the iPSCs were consistent with that of the patient.The iPSCs could be induced to differentiate into skeletal muscle cells in vitro,which expressed the pathogenic gene DUX4 and its regulatory genes.Conclusion The PBMCs from one FSHD patient can be reprogrammed into iPSCs,which can be differentiated into disease-related myogenic progenitor cells and myotubes.This provides a useful cell model for in vitro studies of the pathogenesis of FSHD and a tool for the effective treatment of FSHD.

Objective To investigate the knowledge,demand,and use of clinical practice guide-lines(CPGs)among anesthesia professionals in Gansu province,and to explore the strategies and barriers during the implementation process.Methods A questionnaire survey was conducted to investigated the knowledge,demand,and use of CPGs,as well as the strategies and barriers during the process of guideline implementation.Statistical analysis was applied to the collected data.Results A total of 339 valid question-naires were collected,96.8%of the respondents were aware of the guidelines,and the majority of the re-spondents(86.4%)consulted the guidelines when they encountered problems in clinical practice.The main barriers for guideline utilization were identified as lack of convenience(70.2%),limited availability chan-nels(64.3%)or restricted access rights(56.9%)to obtain the guidelines,inadequate training(31.3%),and language barriers(21.5%).Multiple forms of assisting guideline use and opening up guideline access were considered by most respondents as important ways to promote guideline implementation.Conclusion Anesthesia professionals in Gansu province demonstrated good levels of awareness and compliance with guidelines.However,the primary barriers to utilization were attributed to the guidelines themselves or diffi-culties in accessing them.It is recommended to establish a national guideline clearinghouse,provide imple-mentation tools,and enhance healthcare professional training to facilitate the promotion and application of guidelines in the future.

Objective:To study the effects of sacubitril valsartan sodium on vascular sclerosis and ventricular remodeling in patients with ischemic cardiomyopathical coronary heart disease.Methods:A prospective research method was adopted. One hundred and eighty-six patients with coronary heart disease who were treated in Hangzhou Ninth People′s Hospital from January to December 2021 were selected and divided into control group and observation group by random digits table method, with 93 cases in each group. The control group adopted routine treatment method of aspirin + metoprolol + nitroglycerin + captopril according to the guideline, while the observation group was additionally treated with sacubitril valsartan sodium on the basis of the control group. The clinical efficacy, vascular endothelial function and hardness, cardiac function, ventricular remodeling and adverse reactions were compared between the two groups.Results:The total effective rate of treatment in observation group was significantly higher than that in control group: 96.77%(90/93) vs. 87.10%(81/93), and there was statistical difference ( P<0.05). After treatment, the brachial artery flow-mediated dilation in observation group was significantly higher than that in control group: (14.46 ± 2.80)% vs. (13.09 ± 2.74)%, the level of endothelin-1 was significantly lower than that in control group: (73.32 ± 9.63) ng/L vs. (77.47 ± 10.35) ng/L, and there were statistical differences ( P<0.05). After treatment, the left ventricular ejection fraction (LVEF) in observation group was significantly higher than that in control group: (50.87 ± 3.52)% vs. (49.72 ± 3.71)%, the left ventricular end-systolic diameter, left ventricular end-diastolic diameter and ventricular remodeling indicators of interventricular septal thickness and left ventricular mass index were significantly lower than those in control group: (38.26 ± 5.18) mm vs. (40.05 ± 5.20) mm, (50.49 ± 4.33) mm vs. (52.08 ± 4.25) mm, (8.95 ± 0.39) mm vs. (9.08 ± 0.41) mm, (118.49 ± 9.58) g/m 2 vs. (121.58 ± 9.62) g/m 2, and there were statistical differences ( P<0.05). There were no statistical differences in the levels of total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol after treatment between the two groups ( P>0.05). There were no statistical differences in the incidences of adverse reactions between the two groups ( P>0.05). Conclusions:Sacubitril valsartan sodium has a good clinical efficacy in the treatment of coronary heart disease, and it can improve cardiac function and vascular sclerosis and reverse ventricular remodeling. In addition, it has no significant adverse reactions and is conducive to disease recovery.

Objective:To explore the diagnostic efficacy of percutaneous lymphatic contrast ultrasound (LCEUS) combined with clinicopathological features in the diagnosis of breast cancer sentinel lymph node (SLN).Methods:A total of 135 breast cancer patients who underwent sentinel lymph node biopsy and axillary lymph node radical resection were prospectively collected in the Affiliated Hospital of Nanjing University of Chinese Medicine from July 2018 to June 2021, and the breast masses and SLNs were evaluated by routine ultrasound, contrast-enhanced ultrasound and LCEUS within one week before surgery. The surgeons recorded the patients′ clinical characteristics before surgeries, and the pathology of the masses and SLNs were recorded after surgeries. Univariate analysis and multivariate Logistic regression analysis were used to explore the correlation between ultrasound clinicopathological features of breast cancer and SLN metastasis, then to establish a model, and evaluate the diagnostic efficacy of the model.Results:Univariate analysis showed that SLN metastasis of breast cancer was associated with age, axillary palpation of enlarged lymph nodes, pathological type of mass, clear hilum of lymph nodes, cortical thickening of lymph nodes, marginal blood flow in lymph nodes, and the appearances of LCEUS(all P<0.05). Multivariate Logistic regression analysis showed age, palpation of axillary lymph nodes and the appearances of LCEUS were independent predictors of SLN properties, the OR values were 6.90 ( P=0.030), 16.06 ( P<0.001) and 12.71 ( P<0.001), respectively. The regression equation was Logit(P)=0.887+ 1.932× axillary lymph node palpation + 2.776× marginal blood flow + 2.542×LCEUS. Conclusions:LCEUS combined with marginal blood flow in lymph nodes and palpation of axillary lymph nodes can help to determine the SLN state.

Objective:To analyze the indications for invasive prenatal diagnosis in the third trimester and summarize the pregnant outcome.Methods:Clinical data of 121 women who underwent invasive prenatal diagnosis in the third trimester in the prenatal diagnostic center of the First Medical Center of Chinese PLA General Hospital from January 2016 to December 2020 was retrospectively analyzed. Different genetic diagnostic methods were used according to different indications. Indications and results of prenatal diagnosis, as well as the complications within two weeks after the invasive procedure, pregnancy outcome, and neonatal follow-up of all the participants were described.Results:Among the 121 cases, 107 cases underwent amniocentesis, seven underwent percutaneous umbilical blood sampling, and seven had both procedures performed at the same time (one underwent thoracocentesis at the same time). Newly identified ultrasound abnormalities in the second and third trimesters were the main indications for prenatal diagnosis, accounting for 99.2%(120/121), of which short limbs and fetal growth restriction accounted for 25.0% (30/120) and 20.0% (24/120), respectively. Genetic abnormalities and congenital diseases were detected in 20 cases with a detection rate of 16.5%(20/121). Among them, there were nine cases of achondroplasia, five cases of pathogenic copy number variations, one case of achondroplasia with pathogenic copy number variation, one trisomy 18, one 47,XXX, one tetrasome mosaicism of 12p, one de novo WTX c. 1072(Exon2) C>Tp.R358X heterozygous mutation, and one fetal hypoproteinemia. In addition, six cases with copy number variation of unknown significance (VUS) were detected, noting for a detection rate of 5.0%(6/121). Among the 20 cases with abnormal detection, 15 were terminated, two delivered prematurely before obtaining the prenatal diagnosis results, one underwent cesarean section before obtaining prenatal diagnostic results and two continued the pregnancies. In the six cases with VUS, one was terminated and the other five continued the pregnancy. Only one case had preterm premature rupture of membranes 2 d after amniocentesis and the incidence rate of complications after all kinds of invasive procedures was 0.8% (1/121). During the neonatal follow-up, postnatal whole exome sequencing revealed monogenetic disorder in two cases with normal prenatal diagnostic results; the patient with 12p chimerism had developmental delay; the one with WTX mutation deceased on the day of born; the rest newborns developed normally. Conclusions:As a relatively safe method, invasive prenatal diagnosis in the third trimester is of great importance and value in reducing the miss diagnostic rate of fetuses with severe genetic diseases and birth defects. The appropriate application of prenatal whole exome sequencing could further help to decrease the miss diagnostic rate of monogenetic disorder.

Inflammatory bowel disease(IBD) is a complex multifactorial disease characterized by chronic recurrent intestinal inflammation.The etiology of IBD has not yet been determined, and relevant studies have focused on the genetic susceptibility, immune response, intestinal microbiome and environmental factors of the host.Studies have found that interleukin-10 receptor A(IL-10RA)plays important roles in the pathogenesis of IBD.IL-10RA can not only affect the intestinal barrier, but also affect the intestinal immune system.Furthermore, the mutation of IL-10RA itself is highly correlated with very early-onset IBD.