Objective To evaluate the effects of Met inhibitor XL-880 on radiosensitivity of breast cancer cells MDA-MB-231.Methods MDA-MB-231 cell lines were assigned to the following treatment groups:control group,radiation group,XL-880 group and combination group.Cell apoptosis,cell cycle distributions and tumorigenicity were investigated by flow cytometry or clonogenic assay.The expression of apoptosis and cell cycle related proteins (p21,Cyclin B1,Bcl-2,Caspase-3 and PARP),and phosphorylation levels of c-Met were measured by Western blot.Results XL-880 combined with radiation significantly decreased the proliferation activity of MDA-MB-231 cells (P ＜ 0.05).Flow cytometry results showed that the rate of G2/M cell were increased with XL-880 (P ＜ 0.05),and the rate were (17.3 ±1.3) ％,(20.0 ± 4.0) ％,(28.5 ± 3.1) ％,(57.0 ± 3.3) ％,respectively.Annexin V/PI double-staining assay showed that XL-880 obviously induced the apoptosis of MDA-MB-231 cells after radiation (P ＜ 0.05),of which the apoptotic rates were (7.3 ±0.9)％,(14.1 ±0.6)％,(35.5 ±4.4)％,(48.2±5.3)％,respectively.XL-880 downregulated the expressions of Cyclin B1 and anti-apoptosis protein Bcl-2,while promoted the expression of apoptosis related protein cleaved Caspase-3 and PARP.Conclusions XL-880 enhance the radiosensitivity of breast cancer cell MDA-MB-231 by inhibiting Met pathway.

Objective To investigate the clinicopathological characteristics and prognosis of lung metastases from breast cancer.Methods The clinical data of 119 breast cancer patients treated at our institution from January 2000 to January 2007 were retrospectively reviewed.Results Among 119 patients with lung metastasis,35.3％ was hormone receptor (HR) +/human epithelial growth factor receptor (HER2)-,17.6％ was HR +/HER2 +,21.8％ was HR-/HER2 + and 25.2％ was trriple negative breast cancer (TNBC).The rate of grade Ⅲ in triple negative breast cancer was higher than the other subtypes(P =0.016).The median overall survival was 60 months (9-141 months),the median time to lung metastases was 29 months (3-99 months),and the median survival after lung metastasis was 33 months (range,6-98 months).The 1-,2-,3-and 5-year survival rate was 72.9％,54.1％,35.1％ and 14.4％.Conclusions TNBC,number of lung metastases,time to lung metastases less than 24 months,and a history of systemic chemotherapy were important factors for prognosis of patients with lung metastases.

OBJECTIVE: To explore the genetic basis for a child with congenital heart disease (CHD) and global developmental delay (GDD). METHODS: A child who was hospitalized at the Department of Cardiac Surgery of Fujian Children's Hospital on April 27, 2022 was selected as the study subject. Clinical data of the child was collected. Umbilical cord blood sample of the child and peripheral blood samples of his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 3-year-and-3-month-old boy, had manifested cardiac abnormalities and developmental delay. WES revealed that he had harbored a nonsense variant of c.457C>T (p.Arg153*) in the NONO gene. Sanger sequencing showed that neither of his parents has carried the same variant. The variant has been recorded by the OMIM, ClinVar and HGMD databases, but not in the normal population databases of 1000 Genomes, dbSNP and gnomAD. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as a pathogenic variant. CONCLUSION The c.457C>T (p.Arg153*) variant of the NONO gene probably underlay the CHD and GDD in this child. Above finding has expanded the phenotypic spectrum of the NONO gene and provided a reference for the clinical diagnosis and genetic counseling for this family.
Humans ; Male ; Computational Biology ; DNA-Binding Proteins ; Genetic Counseling ; Genomics ; Heart Defects, Congenital/genetics* ; Mutation ; Parents ; RNA-Binding Proteins ; Child, Preschool ; Developmental Disabilities/genetics*

Objective To retrospective analyze the use of inpatients taking sacubitril/valsartan in Nanjing Drum Tower Hospital,and to provide references for rational clinical application.Methods The relevant data of inpatients taking sacubitril/valsartan in our hospital were systematically collected from July 2019 to September 2021,and the rationality of drug use was eval-uated.Results A total of 2 682 cases were collected,and 868 cases(32.36%)of them involved 918 times of irrational drug use.The specific situations of irrational drug use included off-label use(182 times),irrational usage and dosage(389 times),irrational conversation of drugs(251 times),and irrational drug use for special populations(96 times).Conclusion The use of sacubitril/valsartan exists in unreasonable situations in our hospital.Clinical pharmacists should participate in medication man-agement to a certain extent,strengthen the pharmaceutical care of patients,and improve the rational rate of drug use.

Objective To identify the blood components of Fuzheng Huayu capsule by ultra performance liquid chromatography-high resolution time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Methods ACQUITY UPLCHSS T3 (2.1 mm × 100 mm, 1.8 μm) was used to chromatographic separation; mobile phase was 0.1% formic acid aqueous solution (A) −0.1% formic acid acetonitrile solution (B). The gradient elution conditions included: 0−3 min, 2% B; 3−18 min, 2%−50% B; 18−22 min, 50%−95% B; 22−25 min, 95% B. The equilibration time was 10 min, the flow rate was 0.40 ml/min, and the analysis time was 25 min. The mass spectrometry was characterized by electrospray ionization by a positive-negative ion mode scan with a range of 100-1 100 m/z. Results 49 components were identified in the serum samples at one time, of which 4 were positive and negative ion modes. Conclusion The blood components of Fuzheng Huayu capsule were clarified by this method, which enriched the scientific connotation of Fuzheng Huayu capsule, and laid the foundation for the in-depth study of the compound.

Objective To evaluate therapeutic effects of dihydrotanshinone Ⅰ on hepatic fibrosis based on liver metabolomics method. Methods 28 rats were randomly divided into four groups including control group, hepatic fibrosis model group and dihydrotanshinone Ⅰ low dose group and dihydrotanshinone Ⅰ high dose group. The dihydrotanshinone Ⅰ treated groups received dihydrotanshinone Ⅰ for 28 days. The rat liver samples were collected and analyzed by liquid chromatography-mass spectrometer (LC-MS). The OPLS-DA pattern recognition analysis of metabolomics differences among the groups and therapeutic effects of dihydrotanshinone Ⅰ on hepatic fibrosis were evaluated. Results 38 metabolites were identified through liver metabolomics analysis. The possible mechanism of hepatic fibrosis was mainly involved glutathione metabolism, melatonin metabolism, amino acid metabolism, lipid metabolism and TCA cycle. The hepatic fibrosis induced by TAA was reversed by dihydrotanshinone Ⅰ. Conclusion Dihydrotanshinone Ⅰ provided satisfactory therapeutical effects on hepatic fibrosis through partially regulating the perturbed glutathione metabolism, melatonin metabolism, amino acid metabolism, lipid metabolism, TCA cycle.

Novel model systems have provided powerful tools for the research of human biology. Despite of being widely used, the conventional research models could not precisely describe the human physiological phenomenon. Organoids are three-dimensional multicellular aggregates derived from stem cells or organ progenitors that could differentiate and self-organize to recapitulate some specific functionalities and architectures of their in vivo counterpart organs. Organoids can be used to simulate organogenesis because of their human origin. In addition, the genomic stability of organoids could be well maintained during long-term amplification in vitro. Moreover, organoids can be cryopreserved as a live biobank for high-throughput screening. Combinatorial use of organoids with other emerging technologies (e.g. gene editing, organ-on-a-chip and single-cell RNA sequencing) could overcome the bottlenecks of conventional models and provide valuable information for disease modelling, pharmaceutical research, precision medicine and regenerative medicine at the organ level. This review summarizes the classifications, characteristics, current applications, combined use with other technologies and future prospects of organoids.
Gene Editing ; Humans ; Models, Biological ; Organoids ; Regenerative Medicine ; Stem Cells

Objective To observe the regulatory effect of roxadustat on lipid metabolism while correcting anemia in hemodialysis patients.Methods Sixty patients with chronic kidney disease(CKD)receiving hemodialysis treatment at Nanjing Drum Tower Hospital and combined with concurrent renal anemia were selected.These included 30 patients receiving erythropoietin(EPO)therapy at a dose of 10 000 U per week,and 30 patients receiving roxadustat treatment at a dose based on body weight.The patients'hemoglobin levels were measured,and data on lipid and iron metabolism-related indicators were collected for statistical analysis.Results After 6 months of treatment,the mean hemoglobin levels of both groups of patients were significantly higher than the baseline levels.The mean hemoglobin level in the roxadustat group was higher than that in the EPO group(114.1±7.88 vs.122.23±10.33,P<0.05),but there was no significant difference in the achievement rate between the two groups(77%vs.93%,P>0.05).The total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and triglycerides(TG)in the roxadustat group decreased significantly(P<0.05),while there was no significant change in the EPO group.Compared with the EPO group,roxadustat showed an improvement in iron metabolism indicators.Conclusion Roxadustat has been shown to improve lipid metabolism while correcting anemia.

Objective To investigate the effect of blood group serology and polymerase chain reaction with sequence-specific primers (PCR-SSP) on identification and genotyping of ambiguous ABO blood group. Methods Eighty suspicious ABO blood group samples were identified by serology and polymerase chain reaction with sequence-specific primers (PCR-SSP). The final blood group type and the strategy of the transfusion of each case were determined according to the results of serology and PCR-SSP. Results 40 cases were confirmed to be subtypes, and the remaining 40 cases were normal types with weakened antigens or missing antibodies due to other reasons. The results of molecular genetic blood group typing based on PCR-SSP were 41 cases of subtypes (There were 3 discrepancies between two methods: one was Ael identified by serological methods, while its gene type was O2O2; one was common type O, while its gene type was BO1; one was type A, while its gene type was AB.) and 39 cases of normal ones. Conclusion Genotyping technology combined with serological typing has an important significance in identification of ABO blood groups.
ABO Blood-Group System/genetics* ; Genotype ; Polymerase Chain Reaction ; Antibodies ; DNA Primers

OBJECTIVE To analyze the research status and development trends of the use of sacubitril/valsartan. METHODS Related literature about the use of sacubitril/valsartan were retrieved from CNKI and the core database of Web of Science. CiteSpace 5.8.R3 software was used to analyze authors， countries/areas， institutions and keywords. RESULTS & CONCLUSIONS Totally 1 193 Chinese literature and 1 060 English literature were included. The number of literature increased， with numerous literature covering the United States （429）， the United Kingdom （185） and China （184）. ZHANG Jing （5） and Solomon S D （118） published the highest number of Chinese and English articles. The authors of Chinese literature had less cooperation while the authors of English literature were in close contact. Dept. of Cardiology in the First Affiliated Hospital of Zhengzhou University （9）， Dept. of Cardiology in the Affiliated Hospital of Xuzhou Medical University （9） and Novartis AG （134） had the highest quantity of publications of Chinese and English literature. The institutions of Chinese literature had a small number of overall publications and less cooperation while the institutions of English literature were closely connected. The clinical efficacy of sacubitril/valsartan for heart failure， hypertension and their complications were research hotspots in Chinese and English literature. Chinese scholars and research teams need to strengthen cooperation and communication in the future， as well as conduct research from the perspectives of sacubitril/valsartan in the treatment of heart failure， hypertension and related complication， the improvement of oxidative stress， and the evaluation of the efficacy of combination therapy with dapagliflozin.