Cytokinesis ; Humans ; Lymphocytes ; pathology ; Micronucleus Tests ; Neoplasms ; genetics ; Risk Factors

PURPOSE: Methylenetetrahydrofolate reductase (MTHFR) has been implicated in lung cancer risk and response to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). However, the results are controversial. We performed meta-analysis to investigate the effect of MTHFR C677T polymorphism on lung cancer risk and response to platinum-based chemotherapy in advanced NSCLC. MATERIALS AND METHODS: The databases of PubMed, Ovid, Wanfang and Chinese Biomedicine were searched for eligible studies. Nineteen studies on MTHFR C677T polymorphism and lung cancer risk and three articles on C677T polymorphism and response to platinum-based chemotherapy in advanced NSCLC, were identified. RESULTS: The results indicated that the allelic contrast, homozygous contrast and recessive model of the MTHFR C677T polymorphism were associated significantly with increased lung cancer risk. In the subgroup analysis, the C677T polymorphism was significantly correlated with an increased risk of NSCLC, with the exception of the recessive model. The dominant model and the variant T allele showed a significant association with lung cancer susceptibility of ever smokers. Male TT homozygote carriers had a higher susceptibility, but the allelic contrast and homozygote model had a protective effect in females. No relationship was observed for SCLC in any comparison model. In addition, MTHFR 677TT homozygote carriers had a better response to platinum-based chemotherapy in advanced NSCLC in the recessive model. CONCLUSION: The MTHFR C677T polymorphism might be a genetic marker for lung cancer risk or response to platinum-based chemotherapy in advanced NSCLC. However, our results require further verification.
Carcinoma, Non-Small-Cell Lung/*drug therapy/enzymology/genetics ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/drug therapy/*enzymology/*genetics ; Methylenetetrahydrofolate Reductase (NADPH2)/*genetics ; Platinum/*therapeutic use ; Polymorphism, Genetic/genetics

Objective To investigate the changes of serum milk fat globule epidermal growth factor 8(MFG-E8) levels in pa-tients with carotid atherosclerosis(CAS) ,and the correlation analysis between MFG-E8 and blood glucose ,blood lipid and inflam-matory factors .Methods From October 2015 to February 2017 ,120 patients with carotid atherosclerosis were selected and divided into control group ,thickening group and plaque group ,40 cases in each group .The levels of blood glucose ,blood lipid ,serum MFG-E8 and other inflammatory factors of the three groups were compared ,and the correlation between serum MFG-E8 and other indica-tors .was analyzed .Results The levels of total cholesterol(TC) ,low-density lipoprotein cholesterol(LDL-C) ,tumor necrosis factor alpha(TNF-α) ,and high sensitive C reactive protein (hs-CRP) in plaque group were significantly higher than those in thickening group and control group ,the difference was statistically significant(P<0 .05);the levels of MFG-E8 and interleukin-10(IL-10) in plaque group were significantly lower than those in thickening group and control group ,the difference was statistically significant (P<0 .05);there was no significant difference in the levels of fasting blood glucose (FPG) ,triglyceride(TG) and high-density lipo-protein cholesterol(HDL-C) between the three groups(P>0 .05) .Serum MFG-E8 was negatively correlated with carotid intima-media thickness ,FPG ,TC ,LDL-C ,TNF-αand hs-CRP(P<0 .05)and positively correlated with TG and IL-10(P<0 .05) ,and there was no correlation between serum MFG-E8 and HDL-C(r=0 .105 ,P=0 .255) .Conclusion Serum MFG-E8 can be used as a new index to assess the severity of CAS and it is worthy of clinical application .

Objective:To investigate the clinical value of radiomics based on computed tomography (CT) examination in preoperative differential diagnosis of pancreatic serous cystadenoma (SCA) and mucinous cystadenoma (MCA).Methods:The retrospective case-control study was conducted. The clinicopathological and imaging data of 154 patients with pancreatic cystic neoplasms who were admitted to the First Affiliated Hospital, Zhejiang University School of Medicine from January 2012 to December 2019 were collected. There were 24 males and 130 females, aged (50±13)years. Of the 154 patients, 99 cases were diagnosed as SCA and 55 cases were diagnosed as MCA. All the 154 patients underwent plain and enhanced CT scan of pancreas before operation. The clinical characteristics, radiology features and radiomics features of all patients were collected to construct the clinical characteristics model, radiology model, radiomics model and fused model. The receiver operating characteristic (ROC) curve of each model was drawn, and those constructed models were evaluated by area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Based on the optimal model, the nomogram was constructed. Observation indicators: (1) establishment and validation of clinical characteristics model; (2) establishment and validation of radiology model; (3) establishment and validation of radiomics model; (4) establishment and validation of fused model; (5) nomogram of fused model. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Results:(1) Establishment and validation of clinical characteristics model: 3 clinical characteristics, including age, symptoms and preoperative serum CA19-9, were selected using multinomial logistic linear regression analysis to construct the clinical characteristics model. Result of the multinomial logistic linear regression analysis was expressed by formula ①: clinical characteristics model score=0.635-0.007×age+0.054×clinical symptoms+0.108×preoperative serum CA19-9. The ROC curve for the test dataset of clinical characteristics model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of clinical characteristics model were 0.611(95% confidence interval as 0.488?0.734, P<0.05), 56.6%, 66.7%, 56.3%, 41.5%, 78.4% for the training dataset and 0.771(95% confidence interval as 0.624?0.919, P<0.05), 77.8%, 63.1%, 88.5%, 80.1%, 76.7% for the test dataset, respectively. (2) Establishment and validation of radiology model: 5 radiology characteristics, including tumor location, the number of tumors, tumor diameter of cross section, lobulated tumor and polycystic tumor (more than 6), were selected using multinomial logistic linear regression analysis to construct the radiology model. Result of the multinomial logistic linear regression analysis was expressed by formula ②: radiology model score=?0.034+0.300×tumor location+0.202×the number of tumors+0.014×tumor diameter of cross section?0.251×lobulated tumor?0.170×polycystic tumor (more than 6). The ROC curve for the test dataset of radiology model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of radiology model were 0.862(95% confidence interval as 0.791?0.932, P<0.05), 78.8%, 81.8%, 77.5%, 62.8%, 90.2% for the training dataset and 0.853(95% confidence interval as 0.713?0.994), P<0.05), 88.9%, 89.4%, 88.5%, 85.0%, 92.0% for the test dataset, respectively. (3) Establishment and validation of radiomics model: 4 categories of a total 1 067 radiomics features were extracted from 154 patients with pancreatic cystic neoplasms, including 7 first-order histogram features, 53 texture features, 848 wavelet features and 159 local binary pattern features. A total of 896 stable radiomics features were retained to construct the model, based on the condition of intraclass correlation coefficient >0.9. After selected by variance threshold and correlation coefficient threshold, 350 radiomics features were retained. Fifty synthetic radiomics features were constructed based on the original features in order to obtain potential radiomics features, and the total number of radiomics features was 400. After analyzed by the five-fold recursive feature elimination, 22 radiomics features were screened out, including 13 wavelet features, 7 synthetic radiomics features and 2 local binary pattern features. The support vector machine algorithm was used to construct the radiomics model. The penalty coefficient 'C' and parameter 'γ' of the radiomics model were 35.938 and 0.077, respectively. The kernel function of the radiomics model was 'radial basis function kernel'. The ROC curve of radiomics model using 5-fold cross validation was drawn. The average AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the radiomics model were 0.870 ( P<0.05), 83.1%, 81.8%, 83.8%, 73.8% and 89.2%, respectively. (4) Establishment and validation of fused model: the fused model was constructed after selecting the tumor location and lobulated tumor of radiology characteristics and radiomics score. Result of the multinomial logistic linear regression analysis was expressed by formula ③: fused model socre=?0.154+0.218×tumor location?0.223×lobulated tumor+0.621×radiomics score. The ROC curve for the test dataset of fused model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of fused model were 0.893(95% confidence interval as 0.828?0.958, P<0.05), 83.7%, 81.8%, 84.5%, 71.1%, 90.9% for the training dataset and 0.966(95% confidence interval as 0.921?0.999, P<0.05), 91.1%, 84.2%, 96.2%, 94.1%, 89.3% for the test dataset, respectively. (5) Nomogram of fused model: the nomogram of fused model was illustrated with the Youden index of 0.416. Conclusion:The prediction model based on the radiomics signature and radiological features extracted from preoperative CT examination can make the differential diagnosis of pancreatic SCA from MCA.

Objective: We predicted the molecular mechanism of Panax notoginseng in the treatment and improvement of scar hyperplasia, by using the methods of network pharmacology and bioinformatics. Methods: We collected of related active constituents and targets of Panax notoginseng by retrieving TCM systems pharmacology database and analysis platform (TCMSP), and collected of related active constituents and targets of scar by Genecards database and OMIM database. Cytoscape 3.6.1 software was used to construct "drugs-chemical components-targets-diseases" interaction network diagram. The protein in teraction network map (PPI) was constructed by STRING database. The key targets were used to analyze gene ontology (GO) enrichment and kyoto encyclopedia of genes and genome (KEGG) pathway enrichment. Results: Totally 7 chemical compponents, including beta-sitosterol, quercetin, Stigmasterol and etc. and 108 targets, including AKT1, JUN, MAPK1, IL6 and ect. Panax notoginseng exerts its effects on scar mainly by acting on signal pathways, including PI3K-AKt signal pathway, MAPK signal pathway, TNF signal pathway and ect. Conclusions Based on the methodology of network pharmacology, this study preliminarily predicted the major targets and pathways Panax notoginseng in the treatment of scar, providing a direction for further studies.

Objective:To investigate the clinicopathological features, immunophenotype and differential diagnosis of clear cell hidradenoma, and to analyze the origin of clear cell hidradenoma and the underlying mechanism.Methods:The clinical data of 23 cases of clear cell hidradenoma who underwent surgical resection in Suzhou Municipal Hospital between December 2017 and July 2021 were retrospectively analyzed. Clinical manifestation, imaging features, pathological features and prognosis of the 23 cases of clear cell hidradenoma were analyzed. Expression levels of epithelial membrane antigen, cytokeratin 20, cytokeratin 7, cytokeratin 14, carcinoembryonic antigen, and gross cystic disease fluid protein 15 were detected by immunohistochemical staining technique using the EnVision system. Periodic acid-Schiff (PAS) staining was performed to visualize glycogen.Results:Among the 23 cases, 8 were male and 14 were female, aged 14-94 years, with a median age of 55 years. The first symptom of clear cell hidradenoma was epidermal bulgels in 18 cases.Contrast ultrasonography showed a subcutaneous cystic solid echo mass with abundant blood flow in the solid part. The tumor histologically consisted of two types of cells: secretory epithelial cells or glandular epithelial cells and clear cells. Twenty cases had tumors with the features of benign clear cell hidradenoma. Two cases had atypical clear cell hidradenoma with atypia and mitosis. One case had malignant clear cell hidradenoma. Tumor cells were positive for epithelial membrane antigen, cytokeratin 7, cytokeratin 14, carcinoembryonic antigen, and gross cystic disease fluid protein 15 and they were Periodic acid-Schiff-positive. Twenty-three patients were followed up for 2-36 months, of which 4 were lost to follow-up and the rest had no recurrence of clear cell hidradenoma.Conclusion:Clear cell hidradenoma is rare and has a good prognosis. Malignant clear cell hidradenoma is rarer and has a poor prognosis. Diagnosis of clear cell hidradenoma is mainly based on comprehensive analysis of pathological features and immunophenotypes. Clear cell hidradenoma should be differentiated from metastatic clear cell carcinoma, spiral adenoma, cortical adenoma, and malignant melanoma.

Objective:To explore the diagnostic performance of ultrasound attenuation imaging (ATI) in grading the degree of hepatic steatosis in metabolic dysfunction-associated fatty liver disease (MAFLD).Methods:The liver gray-scale ultrasound and ATI examinations were performed on 212 subjects who were treated in Zhongshan Hospital Affiliated to Fudan University from August 2020 to March 2021. The attenuation coefficient(AC) values among different degrees of hepatic steatosis were analyzed and the diagnostic performance of ATI was evaluated. Relationships between AC values and clinical characteristics were assessed by Pearson′s correlation analysis.Results:The AC values for normal liver, mild, moderate and severe fatty liver were (0.56±0.05)dB·cm -1·MHz -1, (0.68±0.09)dB·cm -1·MHz -1, (0.82±0.09)dB·cm -1·MHz -1, (0.94±0.09)dB·cm -1·MHz -1, respectively. There were significant differences in AC values among different hepatic steatosis divisions( P<0.008). There was highly significant correlation between AC values and the degree of hepatic steatosis( r=0.860, P<0.01), moderate correlation between AC values and BMI( r=0.425, P<0.01), weak correlation between AC values and HDL-C( r=-0.237, P=0.029), no correlations between AC values and age, TC, TG, LDL-C ( r=0.083, 0.055, 0.133, -0.039, all P>0.05) .The areas under the receiver operating characteristics curve of ATI for mild fatty liver and above, moderate fatty liver and above, severe fatty liver and above were 0.958, 0.962, 0.918; the sensitivity were 90.1%, 95.8%, 94.9%, the specificity were 96.1%, 87.1%, 73.9%, and the cut-off values were 0.666 dB·cm -1·MHz -1, 0.719 dB·cm -1·MHz -1, 0.803 dB·cm -1·MHz -1, respectively. Conclusions:ATI is a reliable and convenient method for evaluating the degree of hepatic steatosis in MAFLD.

Objective To investigate the nutritional status and the clinical outcome of the critically ill chil-dren,and to provide scientific evidence for further clinical nutrition management. Methods Nutritional risk screening was performed on 1183 critically ill children hospitalized at the Intensive Care Unit (ICU),Children′s Hospital of Nanjing Medical University from October 2016 to October 2017 by using the Screening Tool for Risk on Nutritional Sta-tus and Growth (STRONGkids),the ICU including of Pediatric Intensive Care Unit (PICU),Surgical Intensive Care Unit (SICU)and Coronary Care Unit (CCU). Median age of the children was (2. 6 ± 2. 4)years (29 d - 12. 9 years). Nutritional status was estimated,and scores of anthropometric parameters such as weight - for - age Z - score (WAZ)(< 5 years)or body mass index - for - age Z - score (BAZ)(≥5 years)were calculated. The data on inci-dence of infectious complications,duration of ICU stay and mechanical ventilation,the total hospital expenses and in -hospital mortality were recorded. Results Of the 1183 cases,134 children(11. 3％)had low nutritional risk,746 children(63. 1％)had moderate nutritional risk and 303 children(25. 6％)high nutritional risk. The prevalence of se-vere malnutrition,moderate malnutrition and mild malnutrition was 8. 1％ (96 / 1183 cases),8. 2％ (97 / 1183 ca-ses),and 12. 8％ (151 / 1183 cases)respectively. The severe malnutrition group had a higher incidence of high nutri-tional risk than other groups [74. 0％(71 / 96 cases)vs. 67. 0％(65 / 97 cases),40. 4％(61/ 151 cases),12. 6％(106/839 cases)],and the differe-nce was statistically significant (P < 0. 001). The incidence of high nutritional risk in the CCU was higher than that than that in the PICU and SICU,and the difference was statistically significant [36. 5％(96 /263 cases),23. 8％(125 / 524 cases)and 20. 7％(82 / 396 cases)respectively,P < 0. 01]. And the incidence of high nutritional risk was higher in infants[37. 6％(198 / 527 cases)]than those in the other age groups[18. 4％(52 / 282 cases),12. 0％(21 / 175 cases),16. 0％(32 / 199 cases)],and the difference was statistically significant (χ2 = 68. 90, P < 0. 0001). Children with a high nutritional risk had increased incidence of infectious complications [8. 6％(26 / 303 cases)vs. 4. 7％ (35 / 746 cases),3. 7％ (5 / 134 cases)],incidence of mechanical ventilation [66. 0％ (200 / 303 cases)vs. 41. 4％(309 / 746 cases),38. 8％(52 / 134 cases)]and total hospital expenses (￥ 52500 vs. ￥ 39700 and￥ 48700 RMB)compared with those with the moderate or the low nutritional risk,and the differences were statistically significant(all P < 0. 05). There were 16 deaths and 8 deaths (2. 7％)in the high nutrition risk group,which was sig-nificantly higher than those in the moderate nutrition risk group [8 cases (1. 1％)]and the low nutrition risk group [0 case(0)](χ2 = 7. 60,P = 0. 02). Conclusions Moderate or high nutritional risk is seen in the critically ill chil-dren,especially in infants and the children with congenital heart disease. Nutritional risk score is correlated with clinical outcomes. Nutritional risk screening and standard nutritional support are recommended so as to improve clinical treat-ment outcomes.

Objective To investigate the nutritional risk of hospitalized infants with severe pneumonia and its relationship with clinical outcome. Methods Totally 113 infants with severe pneumonia admitted to pediatric intensive care unit (PICU)were enrolled in the study. Nutritional risks were screened by STRONGkids, and the nutritional were assessment with WHO Anthro. Clinical outcomes were recorded and analyzed, including mechanical ventilation, length of PICU stay, total hospital expenses, prognosis, and biochemical test index. Results A total of 44 infants (38.9％) had high nutritional risk, 49 (43.4％) had medium nutritional risk, 20 (17.7％) had low nutritional risk when they admitted to PICU. A total of 59 (52.2％) infants were malnourished when they admitted to PICU. There was a significant correlation between the degree of malnutrition and nutritional risk (r =0.574, P<0.01).The incidence of high nutritional risk was significantly higher in 28d～1year-old group than in 1～3 year-old group (χ2=20.46, P<0.01). Nearly 42.5％(48/113) of the children had congenital disease and had higher incidence of high nutritional risk (χ2=11.375, P=0.003) and higher incidence of malnutrition (χ2=10.083, P=0.001) than those without congenital disease. The rate of mechanical ventilation (P=0.028), the duration of mechanical ventilation (P<0.01), total hospital expenses (P=0.002) and the incidence of poor prognosis(P=0.014) were significantly higher in high nutritional risk group than the low nutritional risk group. The retinol binding protein in the high nutrition risk group was significantly lower than the low nutrition risk group (χ2=6.333, P=0.021). Conclusions High nutritional risk and malnutrition are common in infants with severe pneumonia. Malnutrition and nutritional risk are increased in patients less than 1 year old or suffering from congenital disease. Patients with high nutritional risk are more likely to have worse clinical outcomes. STRONGkids is a valid tool for nutritional risk screening in hospitalized children, and early nutrition support is recommended.

Objective:To explore the clinical characteristics and medical nutritional therapy of 6 patients with late-onset ornithine transcarbamylase (OTC) deficiency.Methods:The clinical features, biochemical data, gene variations and treatment outcomes of 6 children with late-onset OTC deficiency admitted to the Department of Clinical Nutrition, Children′s Hospital of Nanjing Medical University from January 2020 to April 2022 were retrospectively analyzed.The 6 patients were all intervened by a long-term medical nutrition management.Results:Liver dysfunction and hyperammonemia (172.1-348.0 μmol/L) were found in all the 6 children with late-onset OTC deficiency.Serum citrulline decreased in 3 patients (3.95-5.43 μmol/L). Three patients showed increased urine orotic acid (123.48-342.60 mmol/mol Cr). Urine uracil increased in 4 patients (106.77-1 207.26 mmol/mol Cr). Variations of the OTC gene [c.364G>C p. (E122Q), c.1028C>G p. (T343R), c.664-2(IVS6)A>C, c.635G>T p. (G212V), c.929_c.931delAAG p. (E310del), c.829C>T p. (R277W)] were identified in all patients.The 6 children were all managed by individualized medical nutrition program and followed up for a long time.During the follow-up period, 3 cases developed hypoproteinemia, acute metabolic crisis and growth retardation, 3 cases had normal growth and laboratory indicators, and 1 case received liver transplantation after 3 months of nutritional management. Conclusions:The clinical manifestations of OTC deficiency are non-specific.Blood amino acids, urine organic acids and genetic tests are important for the diagnosis.Long-term regular medical nutrition management is helpful to improve the prognosis and quality of life of children.