Transcriptomic comparative study on mouse liver injury caused by ultra-high dose rate irradiation and conventional irradiation / 中华放射医学与防护杂志

Objective:To study the effects of FLASH irradiation (FLASH-RT) and conventional irradiation (CONV-RT) on gene expression profile in mouse liver, in order to provide theoretical basis of the potential mechanism of FLASH-RT.Methods:A total of 11 C57BL/6J male mice were divided into healthy control group (Ctrl group), CONV-RT group and FLASH-RT group according to random number table method. Mouse abdomen was treated with 12 Gy CONV-RT or FLASH-RT. Then the mice were killed by neck removal, and the liver tissues were collected to extract total RNA for transcriptome sequencing (RNA-Seq) that was then analyzed by bio-informatics analysis to investigate the changes of gene expression profiles. The mRNA expression levels of Stat1, Irf9 and Rela were verified by quantitative real-time PCR assay.Results:1 762 differentially expressed genes (DEGs) were identified in group FLASH-RT vs. CONV-RT. Among them, 660 genes were up-regulated and 1 102 genes were down-regulated. 1 918 DEGs were identified in groups FLASH-RT vs. Ctrl. Among them, 728 genes were up-regulated and 1 190 genes were down-regulated. 1 569 DEGs were identified in group CONV-RT vs. Ctrl. Among them, 1 046 genes were up-regulated and 523 genes were down-regulated. According to Gene Ontology (GO) analysis, these DEGs from groups FLASH-RT vs. CONV-RT were involved in various functions including defense response to virus, other organisms in cell components, adenylyltransferase activity in molecular function activity. These DEGs from group FLASH-RT vs. Ctrl were involved in various functions including defense response to other oranisms, endoplasmic reticulum chaperone complex, double-stranded RNA binding and so on. These DEGs from group FLASH-RT vs. CONV-RT were involved in several Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including influenza A, Herpes simplex infection and so on. These DEGs from group FLASH-RT vs. Ctrl were involved in several KEGG pathways including influenza A, NOD-like receptor signaling pathway. Stat1 was likely to be activated by FLASH radiation. The quantitative real-time PCR assay showed that FLASH-RT obviously increased the mRNA expressions of Stat1, Irf9 and Rela ( t=6.62, 2.11, 1.67, P<0.05). Conclusions:FLASH-RT and CONV-RT could alter gene expression profiles in mouse liver tissues, and these DEGs are involved in multiple radiobiological functional pathways. In comparison with CONV-RT, FLASH-RT induces a low level of liver injury, which may due to hypoxia radiation resistance.

Clinical application of laparoscopic sentinel lymph node mapping in early staged cervical cancer / 中华妇产科杂志

Objective:To investigate the application of sentinel lymph node biopsy (SLNB) in early-staged cervical cancer by laparoscopy.Methods:It was a prospective, single-arm, single-center clinical study. Seventy-eight cases of cervical cancer patients were collected from July 2015 to December 2018 at the Fourth Hospital of Hebei Medical University. All the patients were injected with tracer into the disease-free block of cervical tissue after anesthesia by the same surgeon who learned sentinel lymph node (SLN) mapping technique in Memorial Sloan-Kettering Cancer Center, and underwent SLN mapping followed by complete pelvic lymphadenectomy. Moreover, all the dissected lymph nodes were stained with hematoxylin eosin staining (HE) pathological examination. Besides, the negative SLN on hematoxylin-eosin staining were detected by immunohistochemistry cytokeratin staining micro-metastasis. To analyze the distribution, detection rate, false negative rate the sensitivity and negative predictive value of the SLN in early-staged cervical cancer by laparoscopy, and explore the value of SLN mapping in predicting the lymph nodes metastasis in early-staged cervical cancer.Results:The overall detection rate of SLN in cervical cancer was 99% (77/78), bilateral detection rate was 87% (68/78). The average of 12.4 lymph node (LN) and 3.6 SLN were dissected for each patients each side. SLN of cervical cancer were mainly distributed in the obturator space (61.5%, 343/558), followed by external iliac (23.5%, 131/558), common iliac (7.3%, 41/558), para-uterine (3.8%, 21/558), internal iliac (2.2%, 12/558), para abdominal aorta (1.1%, 6/558), and anterior sacral lymphatic drainage area (0.7%, 4/558). Fourteen cases of LN metastasis were found among all 78 cases. There were a total of 38 positive LN, including 26 SLN metastasis and 12 none sentinel LN metastasis. Through immunohistochemical staining and pathological ultra-staging, 1 SLN was found to be isolated tumor cells (ITC), and 5 SLNs were found to be micro-metastases (MIC), accounting for 23% (6/26) of positive SLN. SLN mapping with pathological ultra-staging improved the prediction of LN metastasis in cervical cancer (2/14). Metastatic SLN mainly distributed in the obturator space (65%, 17/26), peri-uterine region (12%, 3/26), common iliac region (15%, 4/26), and external iliac region (8%, 2/26). The consistency of the diagnosis of lymph node metastasis by SLN biopsy and postoperative retroperitoneal lymph node metastasis showed that the Kappa value was 1.000 ( P<0.001), indicated that the metastasis status of SLN and retroperitoneal lymph node were completely consistent. The sensitivity, specificity, accuracy, false-negative rate, and negative predictive value of SLN biopsy in the diagnosis of lymph node metastasis were 100%, 100%, 100%, 0, and 100%, respectively. Conclusions:SLN in early-staged cervical cancer patients were mainly distributed in the obturator and external iliac space, pathalogical ultra-staging of SLN could improve the prediction of LN metastasis. Intraoperative SLN mapping is safe, feasible and could predict the state of retroperitoneal LN metastasis in early-staged cervical cancer. SLNB may replace systemic pelvic lymphadenectomy.

Novel mutations of the SRF gene in Chinese sporadic conotruncal heart defect patients.

BACKGROUND: Conotruncal heart defects (CTDs) are a group of congenital heart malformations that cause anomalies of cardiac outflow tracts. In the past few decades, many genes related to CTDs have been reported. Serum response factor (SRF) is a ubiquitous nuclear protein that acts as transcription factor, and SRF was found to be a critical factor in heart development and to be strongly expressed in the myocardium of the developing mouse and chicken hearts. The targeted inactivation of SRF during heart development leads to embryonic lethality and myocardial defects in mice. METHODS: To illustrate the relationship between SRF and human heart defects, we screened SRF mutations in 527 CTD patients, a cross sectional study. DNA was extracted from peripheral leukocyte cells for target sequencing. The mutations of SRF were detected and validated by Sanger sequencing. The affection of the mutations on wild-type protein was analyzed by in silico softwares. Western blot and real time PCR were used to analyze the changes of the expression of the mutant mRNA and protein. In addition, we carried out dual luciferase reporter assay to explore the transcriptional activity of the mutant SRF. RESULTS: Among the target sequencing results of 527 patients, two novel mutations (Mut1: c.821A > G p.G274D, the adenine(A) was mutated to guanine(G) at position 821 of the SRF gene coding sequences (CDS), lead to the Glycine(G) mutated to Asparticacid(D) at position 274 of the SRF protein amino acid sequences; Mut2: c.880G > T p.G294C, the guanine(G) was mutated to thymine (T) at position 880 of the SRF CDS, lead to the Glycine(G) mutated to Cysteine (C) at position 294 of the SRF protein amino acid sequences.) of SRF (NM_003131.4) were identified. Western blotting and real-time PCR showed that there were no obvious differences between the protein expression and mRNA transcription of mutants and wild-type SRF. A dual luciferase reporter assay showed that both SRF mutants (G274D and G294C) impaired SRF transcriptional activity at the SRF promoter and atrial natriuretic factor (ANF) promoter (p < 0.05), additionally, the mutants displayed reduced synergism with GATA4. CONCLUSION: These results suggest that SRF-p.G274D and SRF-p.G294C may have potential pathogenic effects.

A Rice Black-Streaked Dwarf Virus Replication Curve Model to Evaluate Maize Rough Dwarf Disease Resistance.

Resistance to maize rough dwarf disease (MRDD), a major cause of crop losses, depends on external conditions such as the virus transmission period and the rate of viruliferous small brown planthoppers, Laodelphax striatellus. The precise identification of MRDD contributes to the utilization of resistant germplasm and the cloning of resistant genes. In this study, eight maize varieties were artificially inoculated in a greenhouse with viruliferous planthoppers. The viral titers in maize seedlings were detected by quantitative fluorescence RT-PCR, and the viral replication curves were analyzed by regression. A logistic model fit the Rice black-streaked dwarf virus (RBSDV) replication data for five susceptible varieties well, whereas a linear model fit the data for three resistant varieties. Among the five susceptible varieties, the time points with the maximum replication rates (tIP) of the highly susceptible Ye478 and XH6 were significantly earlier than those of the three susceptible varieties, Mo17, Zheng58, and Zhengdan958. P138, the most highly resistant variety, had the lowest slope of the best fit line, followed by moderately resistant Chang7-2 and Dan 340. The RBSDV replication curve model developed in this study can accurately identify the resistance of maize germplasm to MRDD at the molecular level. Our results also suggested that tIP and the slope of the RBSDV replication curve can be considered new criteria to evaluate maize resistance to MRDD.

Association between leptomeningeal collateral circulation and cerebral infarction in patients with middle cerebral artery stenosis / 中华老年心脑血管病杂志

Objective To study the association between leptomeningeal anastomosis (LMA) collateral circulation and cerebral infarction in patients with middle cerebral artery (MCA) M1-segment stenosis by observing the compensatory characteristics of LMA collateral circulation.Methods One hundred and fourteen MCA M1-segment stenosis patients were divided into cerebral infarction group (n=68) and cerebral infarction-free group (n=46).The hemilateral phenomenon of homolateral anterior cerebral artery (ACA) stenosis and posterior cerebral artery stenosis was assessed and its effect on the incidence of cerebral infarction was studied according to its magnetic resonance angiography.Results The ACA score and MCA stenosis severity were significantly different between cerebral infarction group and cerebral infarction-free group (P＜0.05).Multivariate logistic regression analysis showed that low ACA score and MCA M1-segment stenosis were two independent risk factors for cerebral infarction (OR =0.390,95％ CI:0.154-0.987;OR =2.421,95％CI:1.324-4.428,P＜0.01).Conclusion The incidence of cerebral infarction is low in MCA M1-segment stenosis patients with good ACA collateral circulation.

Relationship of clinical and radiological characteristics with pathogenesis of acute small deep cerebellar infarction / 中华老年心脑血管病杂志

Objective To study the relationship of clinical and radiological characteristics with the pathogenesis of acute small deep cerebellar infarction (SDCI).Methods Ninety-five patients with acute small cerebellar infarction admitted to our hospital from April 2015 to April 2017 were divided into deep cerebellar infarction (DCI) group (n =20) and cortical infarction group (n =75).Their clinical and imaging characteristics were compared.Results The lacunar infarction score,leukoararaiosis score and microbleeds score were significantly higher [2 (1,2)score vs 1 (0,1) score,P=0.001;3(2,4)score vs 1(1,2)score,P=0.000;30.0％ vs 6.7％,P=0.041] while the incidence of AF and carotid or basilar artery atheromatous sclerosis was significantly lower (5.0％ vs 30.7 ％,P =0.040;15.0 ％ vs 40.0 ％,P =0.037;20.0 ％ vs 60.0 ％,P =0.001),the incidence of small artery lesions was significantly higher while that of atherosclerotic and cardiogenic throm bosis was significantly lower in DCI group than in cortical infarction group (P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that lacunar cerebellar infarction and cerebral microbleeds were the independent risk factors for DCI (OR=3.233,95％CI:1.538-6.795,P=0.002;OR=8.123,95％CI:2.182-5.301,P=0.009) and that DCI was positively related with small artery lesions (OR=5.481,95％CI:1.811-19.815,P=0.006).Conclusion SDCI is induced by small vessel lesions.

Risk factor analysis of postoperative complications in patients with emergency general surgery / 临床麻醉学杂志

Objective To investigate the relationship between the occurrence of adverse events during operation and postoperative complications in emergency general surgery patients, and to analyze the risk factors of postoperative complications.Methods We retrospectively analyzed 689 e-mergency general patients undergoing general anesthesia emergency surgery during the period of Sep 1,2015 to Sep 1,2016 in the First Affiliated Hospital of Nanjing Medical University.The clinical fac-tors that may influence the outcomes and postoperative complications were collected and analyzed using univariate analysis and multivariate Logistic regression analysis.Results Among the 689 patients enrolled in the study,there were 165 (23.9%)patients who had major complications within 30 days after surgery.The most common postoperative complications were respiratory complications (40.6%).The inde-pendent risk factors of postoperative complications including age (OR 1.880,95%C I 1.448-2.440),ASA classification (OR 3.303,95%C I 2.303-4.736),intraoperative hypotension duration more than 20 minutes (OR 2.501,95%C I 1.387-4.510),intraoperative rapid arrhythmia (OR 2.173,95% C I 1.002-4.711) and surgical level (OR 1.814,95% C I 1.060-3.103).Conclusion Emergency general surgery in patients with intraoperative hypotension duration more than 20 minutes and the occurrence of rapid arrhythmia are independent risk factors for postoperative complications.During the circulation man-agement of emergency surgical patients,the reduction of systolic blood pressure in the operation should be controlled within 20% of the base value to reduce the risk of postoperative complications.