[HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems].

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

[Hospitalization costs of pediatric community-acquired pneumonia in Shanghai].

Objective: To investigate the epidemiology and hospitalization costs of pediatric community-acquired pneumonia (CAP) in Shanghai. Methods: A retrospective case summary was conducted on 63 614 hospitalized children with CAP in 59 public hospitals in Shanghai from January 2018 to December 2020. These children's medical records, including their basic information, diagnosis, procedures, and costs, were extracted. According to the medical institutions they were admitted, the patients were divided into the children's hospital group, the tertiary general hospital group and the secondary hospital group; according to the age, they were divided into <1 year old group, 1-<3 years old group, 3-<6 years old group, 6-<12 years old group and 12-18 years old group; according to the CAP severity, they were divided into severe pneumonia group and non-severe pneumonia group; according to whether an operation was conducted, the patients were divided into the operation group and the non-operation group. The epidemiological characteristics and hospitalization costs were compared among the groups. The χ2 test or Wilcoxon rank sum test was used for the comparisons between two groups as appropriate, and the Kruskal-Wallis H test was conducted for comparisons among multiple groups. Results: A total of 63 614 hospitalized children with CAP were enrolled, including 34 243 males and 29 371 females. Their visiting age was 4 (2, 6) years. The length of stay was 6 (5, 8) days. There were 17 974 cases(28.3%) in the secondary hospital group, 35 331 cases (55.5%) in the tertiary general hospital group and 10 309 cases (16.2%) in the children's hospital group. Compared with the hospitalizations cases in 2018 (27 943), the cases in 2019 (29 009) increased by 3.8% (1 066/27 943), while sharply declined by 76.2% (21 281/27 943) in 2020 (6 662). There were significant differences in the proportion of patients from other provinces and severe pneumonia cases, and the hospitalization costs among the children's hospital, secondary hospital and tertiary general hospital (7 146 cases(69.3%) vs. 2 202 cases (12.3%) vs. 9 598 cases (27.2%), 6 929 cases (67.2%) vs. 2 270 cases (12.6%) vs. 9 397 cases (26.6%), 8 304 (6 261, 11 219) vs. 1 882 (1 304, 2 796) vs. 3 195 (2 364, 4 352) CNY, χ2=10 462.50, 9 702.26, 28 037.23, all P<0.001). The annual total hospitalization costs of pediatric CAP from 2018 to 2020 were 110 million CNY, 130 million CNY and 40 million CNY, respectively. And the cost for each hospitalization increased year by year, which was 2 940 (1 939, 4 438), 3 215 (2 126, 5 011) and 3 673 (2 274, 6 975) CNY, respectively. There were also significant differences in the hospitalization expenses in the different age groups of <1 year old, 1-<3 years old, 3-<6 years old, 6-<12 years old and 12-18 years old (5 941 (2 787, 9 247) vs. 2 793 (1 803, 4 336) vs. 3 013 (2 070, 4 329) vs. 3 473 (2 400, 5 097) vs. 4 290 (2 837, 7 314) CNY, χ2=3 462.39, P<0.001). The hospitalization cost of severe pneumonia was significantly higher than that of non-severe cases (5 076 (3 250, 8 364) vs. 2 685 (1 780, 3 843) CNY, Z=109.77, P<0.001). The cost of patients who received operation was significantly higher than that of whom did not (10 040 (4 583, 14 308) vs. 3 083 (2 025, 4 747) CNY, Z=44.46, P<0.001). Conclusions: The number of children hospitalized with CAP in Shanghai decreased significantly in 2020 was significantly lower than that in 2018 and 2019.The proportion of patients from other provinces and with severe pneumonia are mainly admitted in children's hospitals. Hospitalization costs are higher in children's hospitals, and also for children younger than 1 year old, severe cases and patients undergoing operations.

[Application of combined detection of multiple pathogens in diagnosis and treatment of coronavirus disease 2019].

Due to the wide variety of pathogens causing respiratory tract infection and the close symptoms, coronavirus disease 2019 (COVID-19) needs to be differentiated from other common infections. Early comprehensive detection and accurate identification of respiratory infection pathogens is of great value for early diagnosis, curative effect, as well as monitor of the diseases. Combined detection of multiple pathogens can quickly and accurately detect and distinguish the pathogens, then provide rapid and reliable laboratory diagnostic basis for further treatment. This article elaborates the application and development of multiplex detection assay in the diagnosis of COVID-19 according to the recent research.

Developmental changes of free amino acids in amniotic, allantoic fluids and yolk of broiler embryo.

1. A study was conducted to evaluate the developmental changes of protein and free amino acid concentrations in amniotic, allantoic fluids and yolk during the incubation period of broiler eggs.2. A total of 120 Cobb 500 fertile eggs were individually weighed and then placed in an incubator. On incubation day: 8, 11, 13, 14, 16, and/or 18, amniotic, allantoic fluids and yolk were collected from 20 eggs for analysis of protein content and free α-amino acid concentration in allantoic and amniotic fluids and yolk.3. The total protein concentration in amniotic fluid increased from d 11 of incubation, and reached a peak at d 16 (69.85 g/l; P < 0.01), then declined at d 18 (P < 0.05). The total protein concentration in allantoic fluid increased with age of the embryo (P < 0.01). Crude protein concentration in yolk decreased (P < 0.05) from d 0 to 8, then increased gradually from d 8, and reached a peak at d 16 (P < 0.05). The concentration of most free amino acids in amniotic and allantoic fluids and yolk was related to embryo weight. Amniotic fluid amino acids gradually increased from d 13 to 18, with arginine being the most abundant at d 11 and 14. Glutamate was the most predominant amniotic fluid amino acid at d 16 and 18. From d 13 to 18, the concentrations of most α-amino acids in allantoic fluid increased, and reached a peak at d 18 (aspartate, 373 µmol/l; asparagine, 519 µmol/l; glutamine, 1230 µmol/l; threonine, 537 µmol/l; citrulline, 112 µmol/l; arginine, 2747 µmol/l; alanine, 276 µmol/l; tyrosine, 330 µmol/l; tryptophan, 212 µmol/l; valine, 140 µmol/l; phenylalanine, 102 µmol/l; isoleucine, 92.39 µmol/l; lysine, 1088 µmol/l; P < 0.05). Glutamine was the second most abundant amino acid in allantoic fluid at d 13 and 18. Glutamate was the most abundant α-amino acids at d 8, and 13 in the yolk.4. These results demonstrated that the concentration of free α-amino acids in chicken embryo fluid was related to embryo weight. Arginine, glutamine and glutamate were abundant free α-amino acids in chicken embryo fluid, to support the higher rates of tissue protein synthesis and growth for the embryo.

[Comparison of clinical features between sporadic pancreatic neuroendocrine tumors and those associated with multiple endocrine neoplasia type 1].

Objective: To compare the clinical features of multiple endocrine adenoma type 1 (MEN-1) associated pancreatic neuroendocrine neoplasms (pNENs) as well as sporadic pNENs. Methods: The clinical data of 28 sporadic pNENs patients and 10 MEN-1-related pNENs patients admitted to the First Affiliated Hospital of Nanjing Medical University from January 2010 to June 2021 were collected. Meanwhile, by searching PubMed database and reviewing the clinical data of 20 foreign patients with MEN-1-related pNENs which were reported at the same time.Compare and analyze the similarities and differences between MEN1-associated pNENs and sporadic pNENs in clinical features, such as family history, blood tests, pathological diagnostic indicators, tumor grade, stage and metastasis, treatment and prognosis and so on. Results: A total of 58 pNENs patients were included, and there were 30 MEN1-related pNENs patients and 28 sporadic pNENs patients. Eighteen patients (60%) had a family history of MEN1-related pNENs, and the mean age of onset was (35.3±13.0)years. There were no patients (0) with family history of sporadic pNENs, and the mean age of onset was(55.3±13.4)years. In contrast, the differences in family history, age of onset and NSE were statistically significant(all P<0.05).Among the pathological diagnostic indicators, there were 19 patients (63.3%) with Grade G2 of MEN1-related pNENs, and 25 patients (83.3%) with somatostatin receptor 2(SSTR2) negative. In sporadic pNENs, there were 16 patients (57.1%) with Grade G2 and 9 patients (32.1%) with SSTR2 negative. The differences in pathological grade, immunohistochemistry (Chromogranin A, CD56, and somatostatin receptor 2, SSTR2) between the two groups were statistically significant(all P<0.05). In terms of tumor staging and metastasis, 21 patients with MEN-1-related pNENs had metastasis (70%) and 20 patients with stage Ⅰ and Ⅱ AJCC (71%) in all. Eight patients with sporadic pNENs had metastasis (26.7%) and 8 patients were with stage Ⅰ and Ⅱ AJCC (28.6%). By contrast, the differences in total metastasis rate, AJCC stage and distant metastasis between the two groups were statistically significant(all P<0.05). In terms of treatment and prognosis, there was no statistical significance in the differences between surgical treatment and prognosis (P>0.05), and the difference was also not statistically significant in survival rate between them (P>0.05). Conclusions: There are no significant differences between MEN1-related pNENs and sporadic pNENs in terms of treatment, prognosis, and survival rate, but there are significant differences in clinical features, pathological features and the staging and grading of tumors. The rate of tumor grade, stage and metastasis of sporadic pNENs is higher.

Low levels of organic compound trace elements improve the eggshell quality, antioxidant capacity, immune function, and mineral deposition of aged laying hens.

In the egg production industry, trace elements are required as additional dietary supplements to play vital roles in performance and egg quality. Compared to inorganic microelements (ITs), appropriate dose of organic trace microelements (OTs) are environmentally friendly and sufficient to satisfy the needs of hens. In order to evaluate the extent to which low-dose OTs replace whole ITs, the effects of organic copper, zinc, manganese, and iron compound on the performance, eggshell quality, antioxidant capacity, immune function, and mineral deposition of old laying hens were investigated. A total of 1 080 57-week-old Jing Hong laying hens were assigned to five groups with six replicates of 36 layers each for an 8-week experimental period. The birds were fed either a basal diet (control treatment (CT)) or the basal diet supplemented with commercial levels of inorganic trace elements (IT 100%) or the equivalent organic trace elements at 20%, 30%, and 50% of the inorganic elements (OT 20%, OT 30%, and OT 50%, respectively). Results showed that compared with those in the CT treatment, feeding hens with inorganic or organic microelement diet had significant effects on the eggshell quality, antioxidant capacity, immune function, and mineral deposition of old laying hens (P < 0.05). The eggshell strength and ratio between OT 30%, OT 50%, and IT 100% were similar at weeks 4 and 8, and the eggshell thickness of these groups was also similar at weeks 6 and 8. At week 8, the eggshell colour in OT 50% was darker than that in IT 100%. The mineral content in the eggshells of OT 50% and IT 100% significantly increased (P < 0.001), with no significant difference in effective thickness, mammillary thickness, and mammillary knob width between groups. There were no differences in the malondialdehyde content, total antioxidant capacity, and total superoxide dismutase activity in serum between OT 30%, OT 50%, and IT100%. While the catalase activities, the interleukin-1ß, interleukin-10, immunoglobulin G, and immunoglobulin M concentrations in serum were not significantly different between OT 50% and IT 100%. The mineral contents in the faeces of the organic groups were considerably reduced compared with those in IT 100% (P < 0.001). In conclusion, dietary supplementation with 30-50% organic compound microelements has the potential to replace 100% inorganic microelements in the hen industry for improving eggshell quality, mineral deposition in the eggshell, antioxidant capacity, and immune function, and reducing emissions to the environment without negative effects on laying performance.

[Expression of circ-KEL in acute myeloid leukemia and its regulatory mechanisms in leukemic cells].

Objective: To explore the expression of circ-KEL in patients with acute myeloid leukemia (AML) and the effect and mechanism of circ-KEL on leukemic cells. Methods: The expression of circ-KEL was detected by quantitative real-time polymerase chain reaction in bone marrow mononuclear cells collected from 116 patients with AML and 40 healthy donors. The correlation of circ-KEL expression with the clinical characteristics of patients with AML was further systematically analyzed. The modulations among circ-KEL, miR-335-5p, and LRG1 were predicted through bioinformatics analysis and validated by dual luciferase assay. Cell proliferation and apoptosis were detected using CCK8 and flow cytometry. Results: The expression of circ-KEL was significantly elevated in patients with AML compared with the healthy controls (Relative expression level, -Δct, AML: -7.117±1.831; control: -8.669±1.771, P<0.001) . Moreover, patients with high circ-KEL expression have significantly worse overall survival. The level of circ-KEL in patients with AML was downregulated after chemo-treatment. In addition, circ-KEL could serve as the sponge of miR-335-5p and regulate LRG1. Bioinformatics analysis showed that miR-335-5p correlates with good prognosis and was negatively associated with LRG1. LRG1 could promote cell proliferation and inhibit cell apoptosis. Our results also exhibited the higher expression of LRG1 in patients with AML. Moreover, circ-KEL exerted functional effects via sponging miR-335-5p and regulating LRG1. Conclusion: circ-KEL expresses highly in patients with AML and correlates with poor prognosis, suggesting its important role in the genesis and progress of AML.

[Radioanatomic study on the role of Hadad-Bassagasteguy flap in skull base reconstruction in endoscopic endonasal approach].

Objective: To evaluate the value of Hadad-Bassagasteguy flap (HBF) in endoscopic endonasal approaches (EEA) skull base reconstruction by radioanatomic measurements on CT of the skull base of Chinese adults. The following data in terms of anterior skull base defect and reconstruction, sphenoid platform area and middle skull base defect and reconstruction including sphenoid platform and sella area, clivus area defect and reconstruction, and HBF were collected and assessed. Methods: CT image data of 42 Chinese adults were selected to obtain radioanatomic measurement data related to HBF, anterior skull base defect and reconstruction, middle skull base defect and reconstruction, and defect and reconstruction of clivus area. SPSS 26.0 software was used to analyze the data. Results: The radioanatomic measurement data about HBF and skull base of 42 Chinese adults were obtained. The width of the leading edge of HBF [(37.49±2.86) mm] was 6 mm more than the anterior skull base width at the level of the anterior ethmoidal artery [(30.87±8.61) mm], and the width of the trailing edge of HBF [(42.61±3.95) mm] was also 6 mm more than the anterior skull base width at the level of the sphenoethmoidal junction [(26.79±2.79) mm]. The total length of HBF including the pedicle [(79.68±4.96) mm] was 6 mm more than the length of the anterior skull base reconstruction [(54.06±8.67) mm], and the length of HBF without pedicle [(46.27±3.14)] mm was 6 mm more than the length of anterior skull base defect [(30.87±8.61) mm]. The trailing edge width was 6 mm more than the planum sphenoidal width at the level of the optic strut [(30.87±8.61) mm]. The total length of HBF including the pedicle was 6 mm more than the length of the planum sphenoidal, and the sella reconstruction [(64.44±10.25) mm], also was 6 mm more than the length of the planum sphenoidal reconstruction [(73.61±8.28) mm]. The length of HBF without pedicle was 6 mm more than the length of the planum sphenoidal, and the sella defect [(27.88±3.74) mm], also was 6 mm more than the length of the planum sphenoidal defect [(15.50±3.38) mm]. The width of the leading edge of HBF and the width of the trailing edge were both 6 mm more than the width of clivus reconstruction at the level of the foramen lacerum [(21.68±2.30) mm]. The total length of HBF including pedicles was 6 mm more than the clivus reconstruction length [(67.09±5.44) mm], while the length of HBF without pedicles was also 6 mm more than the clivus defect length [(37.19±3.80) mm]. Conclusions: In this study, the radiosanatomic measurements ensured that HBF could provide sufficient tissue flap for the reconstruction of the anterior skull base and sphenoid plateau and extend the reconstruction area to sella and clivus. Preoperative radiosanatomic measurement can be used to predict the size of HBF required for skull base reconstruction, which provides important guidance for flap harvest.

[Cardiovascular disease risk in diabetes patients aged 40 years old and above in China].

Objective: To evaluate the incidence of cardiovascular disease (CVD), ischemic and hemorrhagic cardiovascular events among Chinese diabetic patients aged 40 years and above with different CVD risk levels. Methods: This study enrolled participants aged 40 years and above in 15 provinces from a prospective cohort study, the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). Participants were categorized into two groups according to the presence or absence of diabetes at baseline. Individuals were further classified into low (0-4.9%), moderate (5%-9.9%) and high risk groups (≥10%), based on predicted ten-year CVD risk using the China-PAR equations. Two followed-up surveys were conducted between 2007 and 2015 to identify CVD events, which were defined as nonfatal acute myocardial infarction, or death due to coronary heart disease, or stroke. Ischemic cardiovascular events included nonfatal acute myocardial infarction, or death due to coronary heart disease, or ischemic stroke. Hemorrhagic cardiovascular events included subarachnoid hemorrhage and intracerebral hemorrhage. The incidences of CVD, ischemic and hemorrhagic cardiovascular events were compared in diabetes and non-diabetes population with different CVD risk levels. Results: This study included 89 209 participants aged 40 years and above, the average follow-up period was 8.5 years. The age was (54.8±9.4) years, and 36 794 (41.2%) were men, and 5 730 (6.4%) were diabetic patients. In diabetes patients aged 40 years and above, 53.7% (3 075/5 730) were at high risk of CVD. Age-and sex-adjusted incidence of CVD, ischemic and hemorrhagic cardiovascular events (1 066.93/100 000 person-years, 824.23/100 000 person-years, and 211.56/100 000 person-years) were significantly lower in diabetes patients than those in non-diabetes population with high CVD risk (1 773.73/100 000 person-years, 1 228.18/100 000 person-years, and 446.49/100 000 person-years) (all P<0.001). Among high CVD risk populations, incidence of ischemic events was significantly higher in diabetic patients than in non-diabetes population (1 638.47/100 000 person-years vs. 1 228.18/100 000 person-years, P<0.001), but incidence of hemorrhagic events tended to be lower in diabetic patients than in non-diabetes population (415.70/100 000 person-years vs. 446.49/100 000 person-years, P=0.635). Incidence of ischemic and hemorrhagic events were similar between diabetes patients and non-diabetes population at low or moderate CVD risk groups (all P>0.05). Conclusions: More than half of diabetes patients aged 40 years and above in China have high CVD risk. The incidence of CVD, ischemic and hemorrhagic cardiovascular events are different in diabetic patients with different CVD risk levels.

Associations between Serum Sex Hormone Concentrations and Telomere Length among U.S. Adults, 1999-2002.

BACKGROUND AND OBJECTIVES: Sex hormone concentrations and telomere length are age related responses of human body, while whether there is a direct relation between sex hormone and telomere length is uncertain. Therefore, we used the data of National Health and Nutrition Examination Survey (NHANES) to quantify their direct association. RESEARCH DESIGN AND METHODS: A total of 710 women aged 35-60 years and 539 men aged 20-85 years were included from two cycles of the NHANES (1999-2002). Telomere length relative to standard reference DNA (T/S ratio) was measured using quantitative polymerase chain reaction method. Seven hormones in serum (5 in men and 2 in women) were assayed. Logistic regressions were used to calculate the odds ratios to evaluate the telomere length-sex hormones association. RESULTS: Men with vigorous physical activity (71.1%) and without history of cardiovascular diseases, diabetes, and lipid-lowering drugs using tended to have a longer telomere length (all P-values < 0.05); while women with longer sedentary time, smaller pregnant or live birth, and with older ages of firth/last birth were likely with longer telomere length (all P-values < 0.05). After adjusted for potential confounders, only anti-Mullerian hormone was positively and stably associated with short leukocytes telomere length in men (OR: 1.098; 95% CI: 1.034, 1.165). We did not detect any significant association of short telomere length with sex hormones in men and women. Discussion and Implications: Serum anti-Mullerian hormone in men was positively and stably associated with telomere length. More large-scaled and well-designed prospective studies are warranted to reconfirm our conclusions.

[Consistency of ALK Ventana-D5F3 immunohistochemistry interpretation in lung adenocarcinoma among Chinese histopathologists].

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer's protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion: There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.

[Prediction model for survival in patients with biliary tract cancer: a development and validation study].

Objective: The aim of the present study was to investigate the survival rate and its prognostic factors for patients with biliary tract cancer, and then a prognostic risk prediction model was constructed to predict the survival probability of patients. Methods: A total of 14 005 patients with biliary tract cancer (including gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater cancer), who were diagnosed between 2010 and 2015 in the US National Cancer Institute Surveillance, Epidemiology, and End Results Program (SEER) were included in the development cohort. The prognostic risk factors of biliary tract cancer were investigated using multivariate Cox regression models. The predictive nomograms were then constructed to predict the overall survival probability of 1, 3, and 5 years, and the predictive discrimination and calibration ability of the nomograms were further evaluated. Meanwhile, 11 953 patients who were diagnosed during 2004 to 2009 from SEER Program were then selected to validate the external predictive accuracy of the prediction models. Results: The 1, 3 and 5-year cumulative survival rates of patients with biliary tract cancer were 41.9%, 20.4% and 15.3%, respectively, in the development cohort. Age greater than 50 years, African Americans and Native Americans and Alaska Natives, higher T, N and M stage and poor histological differentiation grade were risk factors for death, while married status, Asia-Pacific Islanders, insured status and surgery on primary site were protective factors. Gender was not significantly associated with the overall survival. The C statistic of the prediction model was 0.73 (95%CI: 0.72-0.74), and the calibration curve showed that the interaction curves of predictive and actual survival rates of 1, 3 and 5 years were close to the 45 degree diagonal. Results in the validation cohort were similar with those in the construction cohort, with a C statistic of 0.70 (95%CI: 0.69-0.72), indicating high external applicability of the prediction model. Findings from gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater cancer are in consistent with the overall biliary tract cancer. Conclusions: The survival rate of patients with biliary tract cancer is relatively poor, and the survival prediction model based on prognostic factors has high prediction accuracy. In the future, this prognostic prediction model could be applied to clinical practice to guide individualized treatment for patients with biliary tract cancer.

Efficient high-power dual-wavelength lime-green Nd:YVO4 lasers.

An efficient high-power dual-wavelength lime-green Nd:YVO4 self-Raman laser is inventively developed by using two different lithium triborate (LBO) crystals. The first and second LBO crystals are employed to generate the 559 nm lime and 532 nm green lasers, respectively. The temperature of the first LBO crystal is fixed at the optimal phase matching, whereas the temperature of the second LBO crystal is tuned to flexibly control the relative strengths between the 532 and 559 nm waves. When the temperature of the second LBO crystal is set for the maximal total output power, the 532 and 559 nm output powers, respectively, are 7.1 and 2.9 W at a pump power of 31.6 W, corresponding to a conversion efficiency of 31.6%. When the temperature is controlled for the balanced output, the 532 and 559 nm powers, respectively, are 4.3 and 4.2 W at a pump power of 31.6 W, corresponding to a conversion efficiency of 26.9%.

Neuronal activity of the medulla oblongata revealed by manganese-enhanced magnetic resonance imaging in a rat model of gastroesophageal reflux-related cough.

We investigated neuronal activity of the medulla oblongata during gastroesophageal reflux-related cough (GERC). A rat model of GERC was generated by perfusing HCl into lower esophagus and inducing cough with citric acid. The HCl group rat was received HCl perfusion without citric acid-induced cough. The saline control rat was perfused with saline instead and cough was induced. Citric acid-induced cough rat was only induced by citric acid. Blank group rats were fed normally. Fos expressions were observed in medulla oblongata nuclei using immunohistochemistry. Manganese-enhanced magnetic resonance imaging (MEMRI) was performed to detect the Mn(2+) signal following intraperitoneal injection of MnCl(2). HCl perfusion and citric acid-induced cough caused Fos expressions in the nucleus of solitary tract (nTS), dorsal motor nucleus of the vagus (DMV), paratrigeminal nucleus (Pa5), and intermediate reticular nucleus (IRt), which was higher than HCl group, saline control group, citric acid-induced cough group, and blank group. A high Mn(2+) signal was also observed in most of these nuclei in model rats, compared with blank group animals. The Mn(2+) signal was also higher in the HCl, saline and citric acid-induced cough group animals, compared with blank group animals. The study showed medulla oblongata neurons were excited in a HCl perfusion and citric acid-induced cough rat model, and nTS, DMV, Pa5 and IRt neurons maybe involved in the cough process and signal integrate.

Pre-existing Symptoms and Healthcare Utilization Prior to Diagnosis of Neuroendocrine Tumors: A SEER-Medicare Database Study.

The incidence and prevalence of neuroendocrine tumors (NETs) are continually increasing. While it is known that NET symptoms often predate diagnosis, their prevalence and impact on resource utilization and costs are largely unknown. We identified 9,319 elderly patients diagnosed with NETs between 1/2003 and 12/2011 from the Surveillance, Epidemiology and End Results (SEER)-Medicare. We examined the patients' conditions potentially associated with NET, resource utilization and costs during the year before diagnosis. We found that NET patients were more likely to have diagnoses of hypertension (63.8% vs. 53.3%), abdominal pain (22.2% vs. 7.6%), heart failure (11.7% vs. 8.0%), diarrhea (5.8% vs. 1.8%), peripheral edema (5.4% vs. 3.8%) and irritable bowel syndrome (1.2% vs. 0.5%) compared to the non-cancer control group. They also had much higher resource utilization including number of outpatient visits (mean: 22.1 vs. 17.2), percentage with ER visits (20.9% vs. 11.6%), and hospitalizations (28.4% vs. 17.0%). Similarly, NET patients incurred significantly higher total (mean: $14602 vs. $9464), outpatient (mean: $5987 vs. $4253), and inpatient costs (mean: $8615 vs. $5211). This first population-based study on the pre-diagnosis symptoms and healthcare utilization found that NET patients were more likely to have certain conditions and incur higher resource utilizations and costs.

[The relationship between physical activity and incident hypertension in rural Chinese].

Objective: To investigate the relationship between physical activity (PA) and the risk of incident hypertension among population in rural areas of China. Methods: The Community Intervention of Metabolic Syndrome in China & Chinese Family Health Study (CIMIC) was conducted in 2007-2008. Data on PA, smoking, drinking, blood pressure and other variables were obtained at baseline. Then the follow-up study of incident hypertension was performed during 2012-2015. A total of 41 457 participants aged ≥18 years and free from hypertension at baseline were included in the final analyses. PA was calculated as metabolic equivalent (MET) for each participant. Cox proportional hazard models were used to explore the relationship of PA with incident hypertension according to the quartiles of PA. Results: A total of 6 780 participants developed hypertension during an average follow up of 5.8 years. The annual incidence of hypertension was 2.80%. Compared to participants in the first quartile of PA, HR (95%CI) of incident hypertension decreased with the level of PA of 0.92 (0.86, 0.99), 0.72 (0.67, 0.77) and 0.70 (0.65, 0.75) for the 2(nd), 3(rd) and 4(th) quartile, respectively (P(trend)<0.001). In subgroup analyses, compared to the first quartile, hazards of hypertension among normotensive participants (systolic blood pressure less than 120 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure less than 80 mm Hg) in the 2(nd), 3(rd) and 4(th) quartile were 0.82 (0.70, 0.95), 0.73 (0.63, 0.85) and 0.78 (0.67, 0.90), respectively (P(trend)=0.002). Among participants with prehypertension (systolic blood pressure from 120 to 139 mmHg and/or diastolic blood pressure from 80 to 89 mmHg), similar trend for the relationship of PA and incident hypertension was also found with HR (95%CI) of 0.94 (0.87, 1.01), 0.71 (0.65, 0.77) and 0.66 (0.61, 0.71) for the 2(nd), 3(rd) and 4(th) quartile, respectively (P(trend)<0.001). Conclusion: There was linear trend association between PA and incident hypertension. Increased PA in daily life may be a protective factor against hypertension.

Accuracy and reliability of digital craniofacial measurements using a small-format, handheld 3D camera.

OBJECTIVES: Craniofacial assessments often involve three-dimensional facial imaging using an expensive camera with 6 SLR lenses to analyse the positions and relations of anatomic landmarks. Recently, a 3D small-format, handheld camera was developed; however, the accuracy and reliability of this system are largely unknown. The purpose of this study was to evaluate the accuracy and reliability of this system. MATERIALS & METHODS: A total of 30 sets of evaluations were completed by 2 examiners on 5 human subjects, using 3 different methods: direct callipers, 3D handheld camera and conventional tripod 3D camera images. Each evaluation included 29 anthropometric landmarks that were used as reference points for facial analysis. Two examiners marked the landmarks directly on the faces and measured linear distances using the 3 measurement methods. RESULTS: Accuracy analysis was performed for handheld vs direct calliper vs conventional camera measurements. Each of these analyses yielded a grand mean of correlation coefficients of .98. Bias measurements revealed that the handheld and conventional camera methods yielded larger measurements than direct callipers (with a mean difference of 1.74, 1.56 mm, respectively, for rater 1 and 0.94, 1.02 mm, respectively, for rater 2). When compared to one another, both the handheld camera and the conventional camera methods yielded similar values for most measurements, with the average overall difference between these modalities of 0.03 mm for rater 1 and 0.07 mm for rater 2. CONCLUSIONS: The 3D handheld camera showed high accuracy and reliability in comparison with traditional models, indicating that this system may provide a useful tool in craniofacial anthropometry.

[The association of fruit and vegetable intake with the changes of serum lipid levels in middle-aged and older Chinese population].

Objective: To investigate the association of fruit and vegetable intake with long-term changes of serum lipid levels in middle-aged Chinese and older Chinese population. Methods: The study analyzed the data collected in the 2004 and 2007-2008 cohorts of China Multicenter Collaborative Study of Cardiovascular Epidemiology. Finally, 4 495 participants from 10 groups in various regions of China, who both were followed up in the two cohorts, were included for data analysis. They were aged 41-66 years in 2004. Fruit and vegetable consumption were collected with a simple food frequency questionnaire. The percent changes (Δ%) of serum TC, TG, HDL-C and LDL-C between the two surveys were calculated. Multivariate linear regression models were used to estimate the association of fruit and vegetable intake in 2004 with percentage changes of serum lipid levels during the two surveys. Results: The proportions of individuals who consumed fruits <250, 250-499 and ≥500 g/week were 24.0%, 21.8% and 54.2%, respectively. The proportions of individuals who consumed vegetables <500 and ≥500 g/day were 76.7% and 23.3%, respectively. Compared with fruit intake <250 g/week, the regression coefficients (95% CI) of ΔTC% in 250-499 and ≥500 g/week group were -1.54 (-2.71, -0.37) and -1.77 (-2.79, -0.76). And the regression coefficients (95% CI) of ΔLDL-C% were -2.43 (-4.39, -0.48) and -2.89 (-4.59, -1.19). Compared with vegetable intake <500 g/d, the regression coefficients (95%CI) of ΔTC% and ΔLDL-C% in vegetable intake ≥500 g/d group were -1.01 (-1.95, -0.06) and -1.83 (-3.41, -0.24). However, fruit and vegetable intake had no relationship with ΔTG% and ΔHDL-C%. Conclusion: The consumption of fruit and vegetable was inversely related to long-term changes of TC and LDL-C in middle-aged and older population, but no association was found for changes of TG and HDL-C.