177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

OBJECTIVE: To investigate the mechanism by which fibroblasts with high WNT2b expression causes intestinal mucosa barrier disruption and promote the progression of inflammatory bowel disease (IBD). METHODS: Caco-2 cells were treated with 20% fibroblast conditioned medium or co-cultured with fibroblasts highly expressing WNT2b, with the cells without treatment with the conditioned medium and cells co-cultured with wild-type fibroblasts as the control groups. The changes in barrier permeability of Caco-2 cells were assessed by measuring transmembrane resistance and Lucifer Yellow permeability. In Caco-2 cells co-cultured with WNT2b-overexpressing or control intestinal fibroblasts, nuclear entry of β-catenin was detected with immunofluorescence assay, and the expressions of tight junction proteins ZO-1 and E-cadherin were detected with Western blotting. In a C57 mouse model of dextran sulfate sodium (DSS)-induced IBD-like enteritis, the therapeutic effect of intraperitoneal injection of salinomycin (5 mg/kg, an inhibitor of WNT/β-catenin signaling pathway) was evaluated by observing the changes in intestinal inflammation and detecting the expressions of tight junction proteins. RESULTS: In the coculture system, WNT2b overexpression in the fibroblasts significantly promoted nuclear entry of β-catenin (P < 0.01) and decreased the expressions of tight junction proteins in Caco-2 cells; knockdown of FZD4 expression in Caco-2 cells obviously reversed this effect. In DSS-treated mice, salinomycin treatment significantly reduced intestinal inflammation and increased the expressions of tight junction proteins in the intestinal mucosa. CONCLUSION Intestinal fibroblasts overexpressing WNT2b causes impairment of intestinal mucosal barrier function and can be a potential target for treatment of IBD.
Humans ; Mice ; Animals ; Caco-2 Cells ; beta Catenin/metabolism* ; Culture Media, Conditioned/pharmacology* ; Tight Junctions/metabolism* ; Intestinal Mucosa ; Inflammatory Bowel Diseases ; Tight Junction Proteins/metabolism* ; Inflammation/metabolism* ; Fibroblasts/metabolism* ; Mice, Inbred C57BL ; Glycoproteins/metabolism* ; Wnt Proteins/pharmacology* ; Frizzled Receptors/metabolism*

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%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Objective: To explore the mechanism of intestinal tissue damage induced by macrophages activated by WNT2B high-expressed fibroblasts. Methods: This study involved biological information analysis, pathological tissue research and cell experimental research. The biological information of the colon tissue from the children with inflammatory bowel disease in previous study was analyzed again with single-cell sequencing. The pathological tissues were collected by colonoscopy from 10 children with Crohn's disease treated in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from July 2022 to September 2022. According to the findings of colonoscopy, tissues with obvious inflammation or ulceration were classified as the inflammatory group, while tissues with slight inflammation and no ulceration were classified as the non-inflammatory group. HE staining was performed to observe the pathological changes of the colon tissues. Macrophage infiltration and CXCL12 expression were detected by immunofluorescence. In terms of cell experiments, fibroblasts transfected with WNT2B plasmid or empty plasmid were co-cultured with salinomycin treated or non-treated macrophages, respectively; the expression of proteins through Wnt classical pathway were detected by western blotting. Macrophages treated with SKL2001 were used as the experimental group, and those with phosphate buffer as the control group. The expression and secretion of CXCL12 in macrophages were detected by quantitative Real-time PCR and enzyme-linked immunosorbent assay (ELISA). T-test or rank sum test were used for the comparison between groups. Results: Single-cell sequencing analysis suggested that macrophages were the main cells in inflammatory bowel disease colon tissue, and there was interaction between WNT2B high-expressed fibroblasts and macrophages. HE staining of the 10 patients ((9.3±3.8) years old, 7 males and 3 females) showed that the pathological score of colon tissue in the inflammatory group was higher than that in the non-inflammatory group (4 (3, 4) vs. 2 (1, 2) points, Z=3.05, P=0.002). Tissue immunofluorescence indicated that the number of infiltrating macrophages in the inflammatory group was significantly higher than that in the non-inflammatory group under high power field of view (72.8±10.4 vs.8.4±3.5, t=25.10, P<0.001), as well as the number of cells expressing CXCL12 (14.0±3.5 vs. 4.7±1.9, t=14.68, P<0.001). In cell experiments, western blotting suggested an elevated level of glycogen synthase kinase-3β phosphorylation in macrophages co-cultured with fibroblast transfected with WNT2B plasmid, and salinmycin could reverse this change. Real-time PCR suggested that the transcription level of CXCL12 in the experimental group was higher than that in the control group (6.42±0.04 vs. 1.00±0.03, t=183.00, P<0.001), as well as the expression and secretion of CXCL12 by ELISA ((465±34) vs. (77±9) ng/L, t=13.21, P=0.006). Conclusion: WNT2B high-expressed fibroblasts can secrete WNT2B protein and activate the Wnt classical signaling pathway thus enhancing the expression and secretion of CXCL12 in macrophages, inducing the development of intestinal inflammation of Crohn's disease.
Child ; Male ; Humans ; Female ; Child, Preschool ; Adolescent ; Crohn Disease ; Inflammatory Bowel Diseases ; Colon ; Inflammation ; Colonoscopy ; Glycoproteins ; Wnt Proteins

Electrocardiography ; Emergency Medical Services ; Humans ; Myocardial Infarction ; Out-of-Hospital Cardiac Arrest ; therapy ; Percutaneous Coronary Intervention ; ST Elevation Myocardial Infarction ; therapy ; Treatment Outcome

Objective The aim of this study is to investigate the effects of cardiac integrin-linked kinase (ILK) overexpression in a rat model of doxorubicin-induced heart failure and the underlying mechanisms.Methods Rat heart failure model was induced by intraperitoneal administration of doxorubicin (6 injections within 2 weeks: total dose =15 mg/kg).Five weeks after the first injection,rats with heart failure were confirmed by echocardiography and then randomly divided into Ad-ILK group (intramyocardially injected with adenoviral vector expressing ILK) and Ad-null group (intramyocardially injected with empty ad-null,n =20 each).After 4 weeks,ILK expression and activity were detected by Western blot,cardiac function was determined by echocardiographic and hemodynamic examinations.Apoptosis was measured by TUNEL analysis and cardiomyocyte proliferation was estimated by phosphohistone-H3 staining.Results Western blot analysis revealed higher expression of ILK as well as the phosphorylation levels of Akt in AdILK hearts as compared with ad-null controls.Four weeks after transfection,LVEF and LVFS were significantly higher in Ad-ILK group as compared with control group [LVEF: (60.56 ± 2.61)％ vs.(51.94±2.28)％,P＜0.05; LVFS: (28.10± 1.83)％ vs.(22.82 ± 1.68)％,P ＜0.05].The LVEDD and LVESD,as well as LVEDP were significantly lower in Ad-ILK group compared with control group [LVEDD: (6.22 ± 0.24) mm vs.(7.15 ± 0.21) mm,P ＜ 0.05 ; LVESD: (4.42 ± 0.23) mm vs.(5.65±0.25) mm,P＜0.05; LVEDP: (12.96±2.10) mmHgvs.(21.45±2.48) mmHg(1 mmHg=0.133 kPa),P ＜0.05].Reduced levels of serum BNP was also seen in the Ad-ILK group.TUNEL analysis showed that ILK treatment significantly inhibited the apoptosis of cardiomyocytes [(0.23 ± 0.02) ％ vs.(0.45 ± 0.04)％,P ＜ 0.05].Moreover,increased cardiomyocyte proliferation was found in Ad-ILK group through the phospho-histone H3 staining [(0.60 ± 0.07) ％ vs.(0.24 ± 0.03) ％,P ＜ 0.01].Conclusion ILK gene therapy improves cardiac function in this rat model of heart failure,and is associated with reduced apoptosis and increased cardiomyocyte proliferation.

OBJECTIVETo develop the national neglect norms for urban primary school students in China.

METHODSAccording to multi-stage stratified cluster sampling principle, 24 cities of 13 provinces (municipalities) in China were selected during December 1 to 31, 2008. A total of 1491 students in grade 1 - 3 and 2236 students in grade 4 - 6 were selected. Questionnaire was designed by authors and the final norms were determined through several statistical analysis methods, such as item analysis method, factor analysis method, reliability analysis method. The reliability analysis and validity analysis were used to test the stability and reliability of the norms. The evaluation criteria of the scale was determined by the percentile method, then the initial development of the norm was completed.

RESULTSThe two questionnaires of grade 1 - 3 and grade 4 - 6 students consisted of 55 and 57 items, respectively, whose item loadings were ranged from 0.301 to 0.687 and 0.321 to 0.730, which met the statistical requirements. For grade 1 - 3 students, the scale's total Cronbach α coefficients was 0.914, the total split-half reliability coefficients was 0.896, the Cronbach α coefficients of four level was above 0.737 except medical and social neglect, split-half reliability was ranged from 0.461 to 0.757; for grade 4-6 students, the scale's total Cronbach α coefficients was 0.916, split-half reliability was 0.883, except social neglect, the Cronbach α coefficients of other level was ranged 0.457 to 0.856, split-half reliability was ranged from 0.500 to 0.798. The total neglect cut-off score of the two scales grade 1-3 and 4-6 were 125 and 155, respectively.

CONCLUSIONThe structure of two norms was reasonable. The scales have good stability and reliability.

Child ; Child Abuse ; prevention & control ; statistics & numerical data ; China ; epidemiology ; Female ; Humans ; Male ; Reproducibility of Results ; Schools ; Students ; Surveys and Questionnaires

OBJECTIVEYersinia enterocolitica is an extracellular pathogen and its related antigens interact with the host immune system. We investigated the difference in immunological characteristics between a highly pathogenic and poorly pathogenic strain of Y. enterocolitica.

METHODSWe used SDS-PAGE and western blotting to characterize lipopolysaccharide (LPS), Yersinia outer membrane proteins (Yops), membrane proteins, and whole-cell proteins from poorly pathogenic Y. enterocolitica bio-serotype 2/O:9, isolated from China, and highly pathogenic bio-serotype 1B/O:8, isolated from Japan.

RESULTSThese two strains of Y. enterocolitica had different LPS immune response patterns. Comparison of their Yops also showed differences that could have accounted for their differences in pathogenicity. The membrane and whole-cell proteins of both strains were similar; immunoblottting showed that the 35 kD and perhaps the 10 kD proteins were immunogens in both strains.

CONCLUSIONThe major antigens of the two strains eliciting the host immune response were the LPS and membrane proteins, as shown by comparing protein samples with reference and purified preparations.

Animals ; Antigens, Bacterial ; genetics ; metabolism ; Bacterial Proteins ; genetics ; metabolism ; Blotting, Western ; Electrophoresis, Polyacrylamide Gel ; Female ; Gene Expression Regulation, Bacterial ; physiology ; Lipopolysaccharides ; metabolism ; Rabbits ; Yersinia enterocolitica ; classification ; metabolism

OBJECTIVETo explore the status of child neglect among rural areas children aged 0 - 6 years in China.

METHODSA total of 7411 rural children aged 0 - 6 years old who were composed of two age groups (3315 children aged 0 - 2 years old and 4096 children aged 3 - 6 years old) were multistage stratified randomly sampled from 84 villages which were representative of 10 provinces of China, in accordance with sex and age in November 2010. To identify the child neglect based on the Neglect Norms for Children Aged 0 to 2 and 3 to 6 Years Old in Rural Areas of China, SPSS 13.0 was employed for analyzing neglect frequency and degree for every group of different age, sex and neglect type (including physical, emotional, educational, medical, safety and social neglects). χ(2) test and analysis of variance were also used.

RESULTSThe degree of child neglect for the children aged 0 - 2 years old was 45.01 ± 7.56, the neglect frequency was 54.9% (1819/3315); the degree of child neglect for the children aged 3 - 6 years old was 44.42 ± 7.57, the neglect frequency was 53.8% (2203/4096). The neglect frequency of children aged 0, 1, 2 years old were 58.5% (654/1117), 52.2% (597/1144), 53.9% (568/1054) (P < 0.05). For children aged 3 - 6 years old, the degrees of emotional and safety neglect for males (44.60 ± 7.86, 36.82 ± 9.03) were higher than females (44.03 ± 7.72, 36.25 ± 9.05) (P < 0.05); and the frequencies of emotional and social neglect for males (16.8% (349/2072), 28.3% (586/2072)) were also higher than females (14.1% (286/2024), 24.8% (503/2024)) (P < 0.05). All children of two age groups suffered neglect mainly on one of the six neglect types (incidences were 20.6% (683/3315) and 22.7% (931/4096)). For 0-2 age groups, the higher neglect frequencies happened in the single-parent family and the remarried family (62.5% (15/24) and 63.2% (12/19)), but for children aged 3 - 6 years old groups, it happened in the single-parent family (60.0%, 27/45).

CONCLUSIONDegree and frequency of child neglect among children aged 0 to 6 years old in the rural areas of China are high, and we should find out risk factors and provide efficient prevention measures.

Child Abuse ; prevention & control ; statistics & numerical data ; Child, Preschool ; China ; Cross-Sectional Studies ; Female ; Humans ; Infant ; Male ; Rural Population ; Surveys and Questionnaires

OBJECTIVETo develop the national neglect norms for rural children aged 3 to 6 years, which are suitable for Chinese situations.

METHODSAccording to the multi-stage stratified cluster sampling principle, 84 towns of 10 provinces or municipalities were selected in China. Children aged 3 to 6 years were surveyed in November 2010, the sample of analysis were 3240 (of whom males were 49.6% (1608/3240) and the Han nationality were 93.3% (3023/3240)). Questionnaire was designed by authors and deleted items that did not meet the requirements through several statistical analysis methods, such as item analysis method, factor analysis method, reliability analysis method. The reliability analysis and validity analysis were used to test the stability and reliability of the norm. The evaluation criteria of the scale was determined by the percentile method, then the initial development of the norm completed.

RESULTSAfter deleting inappropriate items by statistical processing, finally, the scale consisted of 57 items, and included 6 neglected dimensions (physical neglect, emotional neglect, educational neglect, safe neglect, medical neglect and social neglect). Its item loadings ranged from 0.359 to 0.789, which met the statistical requirements. The scale's total Cronbach α coefficients 0.904, the total split-half reliability coefficients were 0.820, the 6 neglect dimensions' Cronbach α coefficients ranged from 0.620 to 0.815, the 6 neglect dimensions' split-half reliability coefficients ranged from -0.034 to 0.789, the scale's parallel reliability were 0.785 and it's re-test reliability were 0.613. After construct validity, external validity and content validity testing, the result showed that this scale could effectively reflect the real neglected status of children investigated. The total neglect cut-off score of this scale were 121.

CONCLUSIONThe scale has good stability and reliability. And it adapts Chinese conditions and it's convenient to operate.

Child Abuse ; diagnosis ; prevention & control ; Child, Preschool ; China ; Female ; Humans ; Male ; Psychological Tests ; Reproducibility of Results ; Rural Population ; Sampling Studies ; Surveys and Questionnaires ; standards