Identification and expression analysis of the YABBY gene family in strawberry / 生物工程学报

YABBY proteins are important transcription factors that regulate morphogenesis and organ development in plants. In order to study the YABBY of strawberry, bioinformatic technique were used to identify the YABBY gene families in Fragaria vesca (diploid) and Fragaria×ananassa (octoploid), and then analyze the sequence characters, phylogeny and collinearity of the family members. The RNA-seq data and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) technique were used to assay the expression patterns of the family members. A green fluorescent protein (GFP) was fused with FvYABBYs and transiently expressed in tobacco leaf cells for the subcellular localization. As the results, six FvYABBY genes and 26 FxaYABBY genes were identified from F. vesca and F.×ananassa, respectively. The FvYABBY genes were grouped into five clades, and five family members were orthologous with AtYABBY genes of Arabidopsis. In F. vesca, all of the FvYABBYs were basically not expressed not expressed in root and receptacle, while FvYABBY1, FvYABBY2, FvYABBY5 and FvYABBY6 were highly expressed in leaf, shoot, flower and achene. In F.×ananassa, FxaYABBY1, FxaYABBY2, FxaYABBY5 and FxaYABBY6 were expressed in achene, and all FxaYABBY were poorly or not expressed in receptacle. Additionally, under the abiotic stresses of low temperature, high salt and drought, the expression of FvYABBY1, FvYABBY3, FvYABBY4 and FvYABBY6 were down-regulated, FvYABBY5 was up-regulated, and FvYABBY2 was up-regulated and then down-regulated. In tobacco leaf cells, the subcellular localization of FvYABBY proteins were in the nucleus. These results provides a foundation for the functional researches of YABBY gene in strawberry.

Difference in bilateral lower limb muscle synergy mode for gait in patients after unilateral anterior cruciate ligament reconstruction / 中国康复理论与实践

ObjectiveTo investigate the difference in bilateral lower limb muscle synergy mode during gait in patients after unilateral anterior cruciate ligament reconstruction. MethodsElectromyography from bilateral lower limb muscles during gait were collected from twelve male and eight female patients after unilateral anterior cruciate ligament reconstruction in Affiliated Hospital of Wuhan Sports University, from April to June, 2023. The data were analyzed using non-negative matrix decomposition algorithm to extract the number of muscle synergies in the affected and unaffected legs, the time to peak activation of muscle synergies and the relative weights of the muscles. ResultsSix types of muscle synergy were identified in the unaffected leg of males during gait, while five types were identified in the affected leg, lacking synergy 2 that mainly from the tibialis anterior muscle. Six types of muscle synergy were identified in both legs in females during gait. There was no significant difference in the time to peak activation of muscle synergies between both legs in males (P > 0.05). However, the time to peak activation of muscle synergies increased in females in the affected leg for synergy 3 and synergy 5 (P < 0.05). The relative weight of the rectus femoris was lower in synergy 1 in the affected leg in males (P < 0.05). For female, the relative weight of the vastus lateralis was higher and the relative weight of the biceps femoris was lower in synergy 2 in the affected leg in females (P < 0.05); while the relative weight of the rectus femoris was lower in synergy 3 (P < 0.05), and the relative weight of the biceps femoris was lower in synergy 6 (P < 0.05). ConclusionMales would freeze the muscle synergy dominating ankle dorsiflexion in affected leg to enhance ankle stability, and reduce the relative weight of rectus femoris during the loading response phase to weaken the knee landing cushioning. However, females would delay the activation of synergies dominating in loading response phase and the mid-stance phase, enhance the relative weight of vastus lateralis during the loading response phase, and reduce the relative weights of rectus femoris in the loading response phase and the relative weight of biceps femoris in the mid-stance phase, to limit knee flexion.

Exploring the Role of DKK1 in the Occurrence of Lung Adenocarcinoma Based on the Analysis of Bioinformatics / 中国肺癌杂志

BACKGROUND@#Lung cancer is the most common malignant tumor in China, lung adenocarcinoma (LUAD) is the main type of lung cancer, which is a serious threat to people's life and health. At present, there are fewer studies on the role of Dikkopf1 (DKK1) in lung adenocarcinoma. The aim of this study was to investigate the role and potential prognostic value of DKK1 in the development of lung adenocarcinoma by bioinformatics methods.@*METHODS@#Several databases, such as genotype-tissue expression (GTEx), The Cancer Genome Atlas (TCGA) and tumor-immune system interactions database (TISIDB), were used to analyze the expression, clinicopathological features, immune cell infiltration, prognosis and methylation of DKK1 in lung adenocarcinoma. Then, linked immune cell infiltration Omics database was used to analyze the co-expressed genes of DKK1 and their functional enrichment. Finally, 59 pathological samples of paraffin-embedded lung adenocarcinoma patients who underwent surgery at the Affiliated Cancer Hospital of Xinjiang Medical University between 2016 and 2017 were collected for the validation of the prognostic value of expression by immunohistochemistry (IHC) test.@*RESULTS@#The results of bioconfidence analysis showed that the expression level of DKK1 in lung adenocarcinoma tissues was higher than that in normal tissues, the expression in advanced cancers was higher than that in early stages, and the experimental validation revealed that among 59 cases of lung adenocarcinoma, there were 15 cases of negative expression (25.4%), 18 cases of weakly positive expression (30.5%), and 26 cases of strongly positive expression (44.1%). The different expression of DKK1 is related to methylation, prognosis and the activities of various immune cells. Functional enrichment shows that DKK1 may be involved in skin development and cell-substrate junction, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis shows that DKK1 is related to ABC transporters. Bioinformatics analysis and clinical case specimens showed that high DKK1 expression was associated with poorer prognosis in patients with lung adenocarcinoma.@*CONCLUSIONS@#High expression of DKK1 in lung adenocarcinoma is associated with poor prognosis. DKK1 is closely associated with tumor immune cell infiltration and pathways. DKK1 can be considered as a potential prognostic marker and a novel target for immunotherapy of lung adenocarcinoma.

Autosomal dominant neurodevelopmental disorders associated with KIF1A gene variants in 6 pediatric patients / 浙江大学学报·医学版

OBJECTIVES@#To analyze the clinical and genetic characteristics of children with autosomal dominant neurodevelopmental disorders caused by kinesin family member 1A (KIF1A) gene variation.@*METHODS@#Clinical and genetic testing data of 6 children with KIF1A gene de novo heterozygous variation diagnosed in Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from the year 2018 to 2020 were retrospectively analyzed. Pathogenic variants were identified based on whole exome sequencing, and verified by Sanger sequencing. Moreover, the effect of variants on three-dimensional structure and stability of protein was analyzed by bioinformatics.@*RESULTS@#Among 6 patients there were 4 males and 2 females, and the age of consultation varied from 7 months to 18 years. All cases had varying degrees of motor developmental delay since childhood, and 4 of them had gait abnormalities or fell easily. In addition, 2 children were accompanied by delayed mental development, epilepsy and abnormal eye development. Genetic tests showed that all 6 cases had heterozygous de novo variations of KIF1A gene, including 4 missense mutations c.296C>T (p.T99M), c.761G>A (p.R254Q), c.326G>T (p.G109V), c.745C>G (p.L249V) and one splicing mutation c.798+1G>A, among which the last three variants have not been previously reported. Bioinformatics analysis showed that G109V and L249V may impair their interaction with the neighboring amino acid residues, thereby impacting protein function and reducing protein stability, and were assessed as "likely pathogenic". Meanwhile, c.798+1G>A may damage an alpha helix in the motor domain of the KIF1A protein, and was assessed as "likely pathogenic".@*CONCLUSIONS@#KIF1A-associated neurological diseases are clinically heterogeneous, with motor developmental delay and abnormal gait often being the most common clinical features. The clinical symptoms in T99M carriers are more severe, while those in R254Q carriers are relatively mild.

Clinical characteristics and genetic analysis of a child with specific type of diabetes mellitus caused by missense mutation of GATA6 gene / 浙江大学学报·医学版

A 2-year-old boy was admitted to Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine in Nov 30th, 2018, due to polydipsia, polyphagia, polyuria accompanied with increased glucose levels for more than 2 weeks. He presented with symmetrical short stature [height 81 cm (－2.2 SD), weight 9.8 kg (－2.1 SD), body mass index 14.94 kg/m2 (P10-P15)], and with no special facial or physical features. Laboratory results showed that the glycated hemoglobin A1c was 14%, the fasting C-peptide was 0.3 ng/mL, and the islet autoantibodies were all negative. Oral glucose tolerance test showed significant increases in both fasting and postprandial glucose, but partial islet functions remained (post-load C-peptide increased 1.43 times compared to baseline). A heterozygous variant c.1366C>T (p.R456C) was detected in GATA6 gene, thereby the boy was diagnosed with a specific type of diabetes mellitus. The boy had congenital heart disease and suffered from transient hyperosmolar hyperglycemia after a patent ductus arteriosus surgery at 11 months of age. Insulin replacement therapy was prescribed, but without regular follow-up thereafter. The latest follow-up was about 3.5 years after the diagnosis of diabetes when the child was 5 years and 11 months old, with the fasting blood glucose of 6.0-10.0 mmol/L, and the 2 h postprandial glucose of 17.0-20.0 mmol/L.

Antagonistic activity and application of Bacillus velezensis strain Bv-303 against rice bacterial-blight disease caused by Xanthomonas oryzae pv. oryzae / 生物工程学报

In this study, a new Bacillus velezensis strain Bv-303 was identified and its biocontrol effect against rice bacterial-blight (BB) disease caused by Xanthomonas oryzae pv. oryzae (Xoo) was investigated. Cell-free supernatant (CFS) of strain Bv-303 under different growth conditions were prepared to test the antagonistic activity and stability against Xoo by the Oxford-cup method in vitro. The antibacterial effect of strain Bv-303 to BB disease in rice were further analyzed in vivo by spraying the cell-culture broth (CCB), CFS and cell-suspension water (CSW), respectively, on the rice leaves inoculated with Xoo. Additionally, rice seeds germination rate and seedling growth under the strain Bv-303 CCB treatment were tested. The results showed that the strain Bv-303 CFS significantly inhibited Xoo growth by 85.7%‒88.0% in vitro, which was also stable under extreme environment conditions such as heat, acid, alkali and ultraviolet light. As tested in vivo, spraying the CCB, CFS or CSW of strain Bv-303 on the Xoo-infected leaves enhanced rice plant resistance to BB disease, with CCB showing the highest increase (62.7%) in disease-resistance. Notably, CCB does not have negative effects on rice seed germination and seedling growth. Therefore, strain Bv-303 has great potential for biocontrol of the rice BB disease.

The value of shear wave elastography in quantitative evaluation of carotid elasticity in type 2 diabetes patients with nonalcoholic fatty liver disease / 中国医师杂志

Objective:To analyze the value of shear wave elastography (SWE) in evaluating carotid artery elasticity in type 2 diabetes mellitus (T2DM) patients with nonalcoholic fatty liver disease (NAFLD).Methods:A total of 98 T2DM patients diagnosed in the Second Affiliated Hospital of Dalian Medical University were selected and divided into three groups according to the results of liver ultrasound examination. 35 patients without NAFLD were in group A, 33 patients with mild NAFLD were in group B, and 30 patients with moderate to severe NAFLD were in group C. All selected individuals showed no plaque formation on carotid ultrasound examination. Left carotid artery intima-media thickness (IMT), carotid artery systolic diameter (Ds), carotid artery diastolic diameter (Dd), and peak systolic velocity (PSV) were measured using conventional two-dimensional and M-mode ultrasound. The stiffness coefficient (β) was obtained through calculation. SWE was used to measure the mean longitudinal modulus of elasticity (MEmean), mean minimum modulus of elasticity (MEmin), and mean maximum modulus of elasticity (MEmax) of the left carotid artery at the end of diastole.Results:There was no statistically significant difference in Ds, Dd, and PSV among the three groups (all P>0.05). Compared with group A and group B, group C had significantly higher IMT, β, MEmean, MEmax, and MEmin (all P<0.05). Compared with the group A, the group B had higher levels of MEmean, MEmax, and MEmin (all P<0.05), there was no statistically significant difference in IMT and β between the groups (all P>0.05). Correlation analysis showed that MEmax, MEmean, and MEmin in each group were positively correlated with β ( r=0.537, 0.543, 0.525, P<0.01), and also positively correlated with HbA 1c ( r=0.456, 0.483, 0.438, P<0.01), but not with IMT (all P>0.05). The intra observer Intraclass correlation coefficient (ICC) of MEmax, MEmean and MEmin measured by SWE was 0.847-0.887, and the inter observer ICC was 0.791-0.934, indicating a good repeatability. Conclusions:SWE can quantitatively evaluate the elasticity of the carotid artery in patients with T2DM and NAFLD.

Diffuse large B-cell lymphoma of thyroid invading the superior mediastinum with hashimoto's thyroiditis: a case report and literature review / 临床耳鼻咽喉头颈外科杂志

This article reports a case of primary thyroid diffuse large B-cell lymphoma involving the superior mediastinum with Hashimoto's thyroiditis admitted to the Department of Otolaryngology and Head and Neck Surgery, First Hospital of Jilin University. This patient underwent right thyroid lobectomy and was transferred to the Department of Hematology of the Oncology Center for 6 courses of chemotherapy with R-CHOP protocol. The postoperative recovery was good, and the patient was regularly followed up for 12 months after the operation. The patient's condition was stable, and CT showed no abnormally high metabolism in the operation area indicating the inhibition of tumor activity, superficial lymph nodes and peripheral blood cells were normal. The case encountered many difficulties in the diagnosis process, and the diagnosis was not confirmed after puncture in two Grade III Class A hospitals in China. There are few patients with primary thyroid diffuse large B-cell lymphoma complicated with Hashimoto's thyroiditis, and it is particularly rare to invade the mediastinum. There is no report in China and abroad in the literature we reviewed. Therefore, this article reports the case and retrospectively analyzes the etiology, clinical symptoms, diagnosis and treatment of primary thyroid lymphoma.

A case of laryngeal carcinoma complicated with Hodgkin's lymphoma / 临床耳鼻咽喉头颈外科杂志

A case of laryngeal cancer complicated with Hodgkin's lymphoma treated in the Department of Otolaryngology Head and neck surgery of the First Hospital of Jilin University was reported. Under general anesthesia, right vertical partial laryngectomy, bilateral neck lymph node functional dissection and temporary tracheotomy were performed. No recurrence was found in laryngoscope and color Doppler ultrasound of neck lymph nodes 3 and 5 months after operation.

Three-dimensional speckle tracking echocardiography in evaluating left ventricular function in patients with triple vessel coronary artery disease without myocardial infarction / 中国医师杂志

Objective:Three-dimensional speckle tracking echocardiography (3D-STE) was used to evaluate the left ventricular function in patients with triple vessel coronary artery disease without myocardial infarction.Methods:60 patients with three vessel disease of coronary heart disease without myocardial infarction treated in the Second Affiliated Hospital of Dalian Medical University from June 2018 to December 2020 were selected. They were divided into two groups according to the results of coronary angiography. There were 31 cases in group B, and the stenosis rate of all triple vessel coronary artery was 50%-<75%; 29 cases in group C, the stenosis rate of all triple vessel coronary artery was ≥75%; Thirty healthy subjects were recruited as the group A. We measured left ventricular (LV) end-diastolic and end-systolic volume (LVEDV, LVESV) and LV ejection fraction (LVEF) using real-time dynamic three-dimensional echocardiography. The LV strain parameters were acquired by 3D-STE, including global longitudinal strain (GLS), global area strain, global radial strain (GRS) and global circumferential strain (GCS). The correlation between 3D-STE parameters and N-terminal proBNP (NT-proBNP), left ventricular end-diastolic pressure (LVEDP) were analyzed by Pearson linear correlation analysis.Results:The LVEDV and LVESV in group A and B were significantly lower than those in group C (all P<0.05), and the absolute values of LVEF, GLS, GRS, GCS and GAS were higher than those in group C (all P<0.05). There were no significant difference in LVEDV, LVESV and LVEF between group B and group A (all P>0.05), while the absolute values of GLS, GCS and GAS in group B were significantly lower than those in group A (all P<0.05). The absolute values of GLS, GRS, GCS and GAS in group C were negatively correlated with NT-proBNP and LVEDP (all P<0.05). The absolute value of GLS in group B was negatively correlated with NT-proBNP ( P<0.05), and the absolute value of GLS, GRS, GCS and GAS was negatively correlated with LVEDP (all P<0.05). Conclusions:Our study shows that 3D-STE can evaluate the LV function in patients with triple vessel coronary artery disease without myocardial infarction through multiple strain parameters.

Predictive value of CT perfusion imaging on the outcome after mechanical thrombectomy in patients with anterior circulation large vessel occlusive stroke / 国际脑血管病杂志

Objective:To investigate the predictive value of CT perfusion imaging (CTP) parameters on the outcome after mechanical thrombosis (MT) in patients with anterior circulation acute ischemic stroke due to large vessel occlusion (LVO-AIS).Methods:The clinical data of patients with LVO-AIS received MT treatment in Taizhou People’s Hospital from July 2019 to June 2021 and achieved modified Thrombolysis in Cerebral Infarction (mTICI) blood flow grade 2b or above were retrospectively enrolled. RAPID software was used to automatically conduct image post-processing to obtain CTP parameters. The patients were divided into good outcome group (≤2) and poor outcome group (>2) according to the modified Rankin Scale score at 90 days after procedure. Multivariate logistic regression analysis was used to screen the CTP parameters that affect the outcomes. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of CTP parameters for poor outcomes. Results:A total of 88 patients with LVO-AIS were enrolled, including 52 males (59.1%), with a median age of 71 years (range 58-78 years), and the median baseline National Institutes of Health Stroke Scale (NIHSS) score of 14 (range, 11-17). Eleven patients (12.5%) received intravenous thrombolytic bridging MT, and 77 (87.5%) received direct MT. Forty-seven patients (53.4%) had good outcomes and 41 (46.6%) had poor outcomes at 90 d after procedure. Univariate analysis showed that there were significant differences in baseline NIHSS score, vascular occlusion site, baseline Alberta Stroke Program Early CT Score, the number of retrieval attempts, V CBF<30%, V Tmax>6 s, V CBF>30%/mismatch volume and hypoperfusion intensity ratio (HIR) between the poor outcome group and the good outcome group (all P<0.05). Multivariable logistic regression analysis showed that atrial fibrillation (odds ratio [ OR] 6.200, 95% confidence interval [ CI] 1.225-31.374; P=0.027), baseline NIHSS score ( OR 1.188, 95% CI 1.00-1.404; P=0.043) and V CBF<30% ( OR 1.079, 95% CI 1.03-1.123; P=0.027) were the independent influencing factors of poor outcomes. ROC curve analysis showed that the areas under the curve of atrial fibrillation, baseline NIHSS score, V CBF<30% and their combined for predicting the poor outcoms were 0.675, 0.739, 0.882 and 0.914, respectively. V CBF<30% had the highest diagnostic efficiency in predicting poor outcomes of the single factor. When the cutoff value was 16 ml, the sensitivity and specificity were 82.9% and 78% respectively. Conclusions:RAPID software analysis parameters based on CTP can be used to predict the clinical outcomes after MT in patients with LVO-AIS. V CBF<30% >16 ml has a higher predictive value for poor outcomes after MT.

Analysis of clinical features in children with McCune-Albright syndrome / 中华实用儿科临床杂志

Objective:To summarize and analyze the clinical features of McCune-Albright syndrome (MAS) in 26 children, to improve the understanding of MAS diagnosis and treatment, and to achieve early clinical diagnosis of MAS.Methods:The clinical data of 26 children with MAS treated in Department of Pediatrics, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from August 2011 to June 2021 were retrospectively analyzed.Their clinical characteristics were summarized and studied. t-test, Mann- Whitney U test, χ 2 test or Fisher′ s exact probability method was used for comparison between groups. Results:(1) Among the 26 MAS patients enrolled, there were 22 females and 4 males.The average onset age of female and male patients was (5.87±2.94) years old and (7.48±3.36) years old, respectively.(2) In female patients, there were 7 cases with the typical triad and 15 cases with the atypical triad.(3) Female patients had the first symptom of vaginal bleeding (8/22) and breast development (14/22). Among the 4 male children, 1 case had " fracture" and 3 cases " lagged behind their peers in height" at the first visit.(4) Compared with the breast development group, the vaginal bleeding group had an earlier onset age[(4.06±1.88) years old vs.(7.82±1.82) years old] ( t=5.023, P<0.001), earlier bone maturation[(1.26±0.07) vs.(1.09±0.13)] ( t=2.933, P<0.05), a greatly lowered predicted adult height[(-2.16±0.98) SDS vs.(-0.96±1.09) SDS]( t=1.352, P<0.05), a lower blood phosphorus level[(1.41±0.14) nmol/L vs.(1.67±0.24) nmol/L] ( t=1.941, P<0.05), and a significantly elevated alkaline phosphatase level[339(313, 656) U/L vs.243(205, 452) U/L] ( U=1.000, P<0.05). All patients (8 cases) in the vaginal bleeding group had fibrous dysplasia of bone.(5) Ten patients progressed to central precocious puberty (CPP). They showed an older average age of onset[(7.27±2.69)years old vs.(4.69±2.68)years old] ( U=44.000, P<0.05), significantly earlier bone maturation at diagnosis[(1.23±0.11) vs.(1.01±0.13)] ( t=1.834, P<0.05), and a lower predicted adult height[(152.00±4.62) cm vs.(162.10±6.91) cm] ( t=3.805, P<0.05), compared with those who did not progress to CPP.(6) Eleven children developed polyostotic fibrous dysplasia of bone, and most common type (8 cases) was polyostotic fibrous dysplasia of bone, primarily at lower limb bones and skulls.(7) Of the 26 children, 20 cases had scattered Café au lait pigments on the skin.The Café au lait pigmented skin lesions in 35% (7/20) cases crossed the midline. Conclusions:With complicated clinical manifestations, MAS is more common and occurs earlier in girls than boys.It is difficult to clinically diagnose MAS in boys due to the insidious onset and atypical symptoms.Female MAS patients with vaginal bleeding as the first symptom usually have an early age of onset, advanced bone age and lower predicted adult height, so they should be monitored and evaluated clinically.Vaginal bleeding is significantly associated with polyostotic fiber dysplasia of bone in MAS patients.Therefore, it is recommended that patients with vaginal bleeding should undergo a routine bone single-photon emission computed tomography scan.This helps understand the situation of occult fiber dysplasia of bone.Patients with later diagnosis and advanced bone age should be aware of the possibility of progression to CPP.

Efficacy of combination of toy and cartoon video-assisted admission in preventing agitation during recovery from general anesthesia in preschool children / 中国实用护理杂志

Objective:To evaluate the efficacy of combination of toy and cartoon video-assisted admission in preventing agitation during recovery from general anesthesia in preschool children.Methods:Totally 96 children who undergoing elective surgery from July 2018 to October 2019 in Guangzhou Women and Children′s Medical Center were divided into experimental group ( n=48) and control group ( n=48). Two groups were admitted to the general preoperative waiting room for 60 minutes before the operation, and children in the experimental group recieved toy and cartoon video combination intervention, while children in the control group were subjected to routine nursing intervention. The children′s agitation was assessed by using Pediatric Anesthesia Emergence Delirium Scale (PAED) when children entered the post-anesthesia care unit (PACU), 10 minutes after in PACU and leave PACU. In addition, the vital signs such as blood pressure, heart rate, respiratory rate of the two groups were also recorded. Results:The emergence time and duration of PACU stay in the experimental group were (17.19±1.76) minutes and (22.47±2.36) minutes, significantly shortern than in the control group (18.36±2.19) minutes and (23.82±2.62) minutes, the difference was statistically significant ( t values were 2.760, 2.546, P<0.05). 10 minutes after in PACU and out of PACU, the PAED scores, systolic pressure, heart rate, respiratory rate was [7.56±1.86, 4.60±1.19, (108.12±10.19)mmHg, (102.72±8.55) mmHg, (112.91±6.10) times/minute, (106.39±6.75) times/minute, (18.87±1.98) times/minute, (17.49±1.68) times/minute], significantly lower than those in the control group [13.40±1.47, 6.71±2.21, (116.73±14.17)mmHg, (107.62±12.44) mmHg, (121.07±8.07) times/minute, (114.69±5.78) times/minute, (20.96±1.86) times/minute, (18.47±1.63) times/minute], the difference was statistically significant ( t values were 2.162-16.332, P<0.05). Conclusion:Toy and cartoon video combine-assisted admission can reduce the agitation and stable vital signs during recovery from general anesthesia in preschool children.

Discovery of thiosemicarbazone derivatives as effective New Delhi metallo-β-lactamase-1 (NDM-1) inhibitors against NDM-1 producing clinical isolates

@#New Delhi metallo-β-lactamase-1 (NDM-1) is capable of hydrolyzing nearly all β-lactam antibiotics, posing an emerging threat to public health. There are currently less effective treatment options for treating NDM-1 positive “superbug”, and no promising NDM-1 inhibitors were used in clinical practice. In this study, structure–activity relationship based on thiosemicarbazone derivatives was systematically characterized and their potential activities combined with meropenem (MEM) were evaluated. Compounds 19bg and 19bh exhibited excellent activity against 10 NDM-positive isolate clinical isolates in reversing MEM resistance. Further studies demonstrated compounds 19bg and 19bh were uncompetitive NDM-1 inhibitors with Ki = 0.63 and 0.44 μmol/L, respectively. Molecular docking speculated that compounds 19bg and 19bh were most likely to bind in the allosteric pocket which would affect the catalytic effect of NDM-1 on the substrate meropenem. Toxicity evaluation experiment showed that no hemolysis activities even at concentrations of 1000 mg/mL against red blood cells. In vivo experimental results showed combination of MEM and compound 19bh was markedly effective in treating infections caused by NDM-1 positive strain and prolonging the survival time of sepsis mice. Our finding showed that compound 19bh might be a promising lead in developing new inhibitor to treat NDM-1 producing superbug.

Endothelin-1 gene Lys198Asn polymorphism and ischemic stroke / 国际脑血管病杂志

Endothelin (ET) is a potent vasoconstrictor peptide produced by endothelial cells, which is closely associated with vascular endothelial dysfunction and cardio-cerebrovascular diseases. Recent studies have shown that ET-1 gene Lys198Asn polymorphism can be used as a new biomarker of cerebrovascular diseases. This article reviews the research progress on the relationship between the gene polymorphism and susceptibility to ischemic stroke, and discusses its clinical significance.

Diagnostic Value of Locally Produced Tumor Markers and Blood Brain Barrier Integrity in Lung Cancer Patients with Leptomeningeal Metastasis / 中国肺癌杂志

BACKGROUND@#Tumor markers (TM) in cerebrospinal fluid (CSF) are useful for diagnosing leptomeningeal metastasis (LM). It has not been fully exploited the diagnostic possibilities of the CSF levels since the basic fact that the TM concentration of CSF depends strongly upon the serum levels as well as upon the condition of the blood brain barrier (BBB). To analyze the intrathecal TM synthesis and evaluate the integrity of BBB can be helpful for the definitive diagnosis of LM. Therefore, the aim of this study was to further explore the clinical value of intrathecal TM synthesis and BBB in the diagnosis for the lung cancer patients with LM.@*METHODS@#Twenty-five lung cancer patients with LM and 57 patients with nonmalignant neurological diseases (NMNDs) admitted to Nanjing Drum Tower Hospital from December 2016 to March 2020 were included. We compared the integrity of BBB and intrathecal TM synthesis between two groups, analyzed the correlation of CSF TM between the detection and intrathecal synthesis, and evaluated serial CSF cytology, the integrity of BBB and intrathecal TM synthesis when intrathecal chemotherapy for one patient.@*RESULTS@#Ninety-four percent LM patients showed the dysfunction of BBB, and all LM patients showed at least one intrathecal synthesized TM in CSF. In one patient, the CSF cytology was negative for the first time, but LM was eventually diagnosed based on the the intrathecal TM synthesis and positive CSF cytology of repeated lumbar puncture. In LM group, no correlation was observed between the detection and intrathecal synthesized TM in CSF. In the control group, only 3.5% (2/57) NMNDs patients had the dysfunction of BBB and no patients had intrathecal TM synthesis, both the differences of which were statistically significant (P<0.05). Finally, evaluating the CSF cytology, integrity of BBB and intrathecal TM synthesis can be used to assess the intracranial treatment effect. Moreover, intrathecal TM synthesis changes earlier than cytology.@*CONCLUSIONS@#The evaluation of intrathecal TM synthesis and integrity of BBB are novel clinical diagnostic tools. In addition, serial measurement of intrathecal synthesized TM may play an important role in monitoring efficacy of lung cancer patients with LM, which is worthy of further promotion and clinical application.

Brain dynamic functional connectivity between default mode network and executive control network by resting state functional MRI in patients with alcohol use disorder / 中华放射学杂志

Objective:To investigate the changes of dynamic functional connectivity between the default mode network (DMN) and executive control network (ECN) in the resting state in patients with alcohol use disorder (AUD).Methods:From September 2018 to June 2019, 23 cases of AUD group and 24 cases of healthy control (HC) group matched with age, gender, education level and handedness were collected at Renmin Hospital of Wuhan University. Mini-mental state examination (MMSE) and Michigan alcoholism screening test (MAST) were performed in all subjects for cognition and alcohol dependence score. All the subjects underwent T 1WI-3D structural imaging and resting state functional MRI (rs-fMRI) examination. Group spatial independent component analysis (ICA) was used to select the independent components of DMN and ECN. Then dynamic changes in the functional connectivity between the DMN and the DMN were obtained by sliding window approach and clustering method. Finally, the independent sample t test was used to compare the difference of general clinical data between the two groups, the linear correlation analysis was conducted in the parameter value and MMSE and MAST scores. Results:Compared with the HC group, the static functional connectivity analysis showed that the precuneus and posterior cingulate gyrus of the DMN were enhanced in the AUD group ( P=0.016, t=2.496). The DMN and ECN functional connectivity showed four different brain activity states, the proportion of state1 increased by 6.81% and state2 decreased by 6.83% in the AUD group, state3 and state4 were relatively stable. In state1, the internal functional connectivity of the DMN in the AUD group was enhanced, while the functional connectivity between DMN and ECN was mainly enhanced. In state2, the internal functional connectivity of the ECN was enhanced, and the connectivity between the DMN and ECN was mainly weakened. The mean dwell of state2 in the AUD group was negatively correlated with the MAST score ( r=-0.433, P=0.039). Conclusions:Dynamic functional connectivity patterns between DMN and ECN have been changed in patients with AUD. Dynamic functional connectivity can reveal transient changes in brain activity, which can provide certain imaging evidence for finding changes in AUD deep brain activity.

Application progress of 18F-FDG PET/CT in bone and soft tissue sarcomas / 中国介入影像与治疗学

The incidence of bone and soft tissue sarcomas is relatively low, but most of them are highly malignant and have poor prognosis. Early diagnosis is the key to improve prognosis. 18F-FDG PET/CT can be used to diagnose and differential diagnose bone and soft tissue sarcoma, tumor classification, determine biopsy site, detect tumor recurrence and metastasis, also to evaluate therapeutic efficacy and prognosis, etc. The application advancements of 18F-FDG PET/CT in bone and soft tissue sarcomas were reviewed in this article.

Different Gene Mutation Spectrum of the Paired CSF and Plasma Samples in Lung Adenocarcinoma with Leptomeningeal Metastases: the Liquid Biopsy Based on Circulating Tumor DNA / 中国肺癌杂志

BACKGROUND@#Leptomeningeal metastasis (LM) are a severe complication of non-small cell lung cancer (NSCLC), and normally accompanied by poor prognosis. For the patients with targetable mutations, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the preferred treatment, but the acquired TKI resistance is inextricable. The aim of this study is to analyze the different gene mutation spectrum and mutation frequency of the cerebrospinal fluid (CSF) and plasma in NSCLC patients with LM, and screen out the drug-resistant mutations so as to guide the choice of treatment accurately.@*METHODS@#The paired CSF and plasma samples were collected from the NSCLC-LM patients with acquired TKI resistance. Next generation sequencing (NGS) was used to detect the gene variations of circulating tumor DNA (ctDNA).@*RESULTS@#A total of 18 NSCLC patients with LM were collected. Of the basic mutations, 11 cases (61.11%) were EGFR, 6 cases (33.33%) were anaplastic lymphoma kinase (ALK), and 1 case (5.56%) was ROS proto-oncogene 1, receptor tyrosine kinase (ROS1). Tumor protein p53 gene (TP53) and mesenchymal-epithelial transition factor (MET) were the two most frequently accompanying mutated genes in CSF ctDNA. The detected mutation rate of CSF samples was higher than that of plasma samples (100.00% vs 66.67%, P=0.006), and the maximum allelic fractions were all higher in CSF than in plasma (P<0.001). Abundant single-nucleotide variations (SNV) and copy number variants (CNV) were detected in CSF, the amount of both of which were more than in blood. In addition, the CSF and plasma samples of patients treated with several TKIs had more SNV mutations than patients who received only a single TKI treatment.@*CONCLUSIONS@#For the patients of NSCLC, ctDNA in CSF could reveal genomic alterations of LM more exactly and overally than it in plasma, thus could be an optimal source of liquid biopsy for guiding therapy, monitoring therapeutic effect, and predicting prognosis.

Identification of Candidate Biomarkers for EGFR-T790M Drug-resistant Gene Mutation in Advanced Lung Adenocarcinoma / 中国肺癌杂志

BACKGROUND@#Osimertinib is approved by Food and Drug Administration for patients with advanced non-small cell lung cancer carrying EGFR-T790M mutations. Osimertinib therapy was missed in many patients who were unable to perform biopsy due to occult lesion progression or weak body. In this study. We hope that some proteins associated with predicting EGFR-T790M resistance could be screened from the serum to provide help for clinical medication. The aim of this study is to explore the protein associated with EGFR-T790M drug resistance gene and provide help for clinical medication.@*METHODS@#In this study, 36 patients with advanced lung adenocarcinoma treated by gefitinib were included. After the disease progression of the patients, biopsy was performed. 18 patients in the EGFR-T790M mutation group and 18 patients in the non-EGFR-T790M mutation group were detected by the ARMS method. Serum of patients with drug resistance was collected, and proteins related to EGFR-T790M resistance were screened by isotopic marker relative and absolute quantitative marker combined with two-dimensional liquid chromatography tandem mass spectrometry proteomics technology.@*RESULTS@#Seventeen different proteins were screened out, including 6 up-regulated proteins and 11 down-regulated proteins associated with EGFR-T790M gene mutation, which were mainly involved in 31 biological processes, 7 cell components and 26 molecular functions. Twelve enrichment pathways were identified, among which the highest enrichment index was the coagulation cascade pathway.@*CONCLUSIONS@#Seventeen proteins associated with EGFR-T790M resistance were found, and proteins involved in the coagulation cascade pathway are expected to be biomarkers associated with predicting EGFR-T790M resistance mutations.