Objective To investigate the mechanism of micellar curcumol (MC) regulating the immune microenvi-ronment of ovarian cancer by promoting the polarization of M2-type macrophages to M1-type in ovarian cancer asci-tes.Methods ① After the mice were divided into groups, a mouse ovarian cancer ascites model was constructed by using the mouse ovarian cancer cell line ID8.Then weight changes were observed, tumor tissue and ascites were collected.The expression of CD86 and CD206 on macrophages of the tumor tissue and ascites was detected by flow cytometry.The expression of protein kinase B (PKB/Akt)/mammalian target of rapamycin (mTOR) was detected by Western blot.②A human monocytic leukemia cell line (THP-1) was induced to transform into M2 macrophage (THP-1 M2 macrophage) in vitro, and then treated with 10μg/ml MC.The apoptosis was detected by flow cytom-etry.The mRNA levels of macrophage mannose receptor (CD206), transforming growth factor-β(TGF-β), inter-leukin (IL)-1β and tumor necrosis factor-α (TNF-α) were detected by qRT-PCR.The expression of CD86 and CD206 was detected by flow cytometry, and Akt/mTOR expression and phosphorylation was detected by Western blot.Results ① In vitro study showed that the average body weight of the MC group was lower than that of the control group.Compared with the control group, CD206 expression of macrophages decreased in tumor tissue and ascites in the MC group, while the expression of CD86 increased.The Akt and mTOR phosphorylation level of mac-rophages in the MC group's ascites was lower than that in control group.②In vivo study showed that there was no difference in apoptosis rate among the groups detected by flow cytometry.The mRNA expression level of CD206, TGF-β and the protein expression level of CD206 in MC group were significantly lower than those in the control group, while the mRNA expression of IL-1β, TNF-α and the protein expression level of CD86 were significantly higher than those in the control group.Compared with the control group, the phosphorylation level of Akt and mTOR in the MC group decreased.Conclusion MC promotes M1 polarization of macrophages in ascites to regulate the immune microenvironment of ovarian cancer, which may be related to the Akt/mTOR pathway.

Objective:To explore the correlation between structural chromosomal abnormality and clinical characteristics of a child featuring gonadal dysplasia.Methods:A 13-year-old child who was admitted to Lianyungang Maternal and Child Health Care Hospital on February 7, 2023 for primary amenorrhoea and occasional abdominal pain was selected as the study subject. Clinical data of the child was collected, and peripheral blood samples of the child and her parents were collected. G-banding chromosomal karyotyping and copy number variation sequencing (CNV-seq) were carried out. "Pseudodual centromere isochromosome X" and "psu idic(X)" were used as keywords to search the CNKI, Wanfang and PubMed databases, and the search period was set as from January 1, 2002 to June 1, 2023. Relevant literature on the structural abnormality of X chromosome was searched and analyzed retrospectively.Results:The child has a height of 153 cm and weighed 45 kg. She has no obvious facial dysmorphism. Laboratory tests showed that she had higher FSH and luteinizing hormone, and lower E2. Ultrasonography showed that she had small ovaries and rudimentary uterus. She was found to have a karyotype of 46, X, psu idic(X)(q21.3)[40]/mos 45, X[3], whilst both of her parents had a normal karyotype. CNV-seq showed that she had a 63.27 Mb deletion in Xq21.32q28 and a 91.59 Mb duplication in Xp22.33q21.32 (mosaicism rate = 74%). A total of 11 relevant literature were retrieved. Clinical phenotypes of patients with similar structural chromosomal abnormalities were diverse, which was closely related to the mosaicism rate of the 45, X karyotype and the location of the breaking point.Conclusion:46, X, psu idic(X)(q21.3)/45, X probably underlay the dysplasia of uterus and ovary and sex hormone abnormalities in this child, while her height was spared. Deletion of Xq21.32q28 is a key factor leading to Turner syndrome-like phenotype such as rudimentary uterus and ovarian dysplasia.

Objective:This study aimed to explore the clinical value of myostatin(MST) and follistatin(FST) as biological biomarkers in evaluating sarcopenia in elderly women.Methods:This was a retrospective cross-sectional study that enrolled 350 females aged 20-89 years who underwent physical examinations in Shanghai Huadong Hospital in 2021. Demographic characteristics, muscle mass, fat mass, bone mineral density, hand grip strength, gait speed, and serum indices of MST and FST were collected.Results:The serum levels of MST did not change significantly with age. However, the serum levels of FST increased with age. In women aged≥60 years, MST was positively correlated with total lean mass and appendicular skeletal muscle index(ASMI; r=0.236, P=0.041; r=0.289, P=0.014), while FST was negatively correlated with ASMI( r=-0.265, P=0.030). In multivariate stepwise regression analysis, after adjusting for age, body mass index, hip bone mineral density, and total fat mass, only FST was independently correlated with ASMI( β=-0.238, P=0.006), while MST was not correlated with ASMI. The receiver operating characteristic curve was plotted using muscle mass reduction as the state variable and serum FST level as the test variable. The area under the curve was 0.753. And when the FST cutoff value was 17.49 ng/mL, the maximum Jordan index was 0.46, with a sensitivity of 77.3% and a specificity of 68.7%. Women aged ≥60 years were divided into three groups based on serum FST levels. Compared to the upper third of the serum FST level group, the low third of the FST level group had a significantly reduced risk of suffering from sarcopenia( OR=0.098, P =0.036). Conclusions:Serum FST lever has a better correlation with muscle mass among elderly women, making it a promising biomarker for evaluating muscle mass.

Objective:To explore the status quo of knowledge, attitude and practice in the posture management of premature infants among nurses in Neonatal Intensive Care Unit (NICU) and related training needs.Methods:This study is a cross-sectional study. From March to April 2022, 207 NICU nurses from 6 ClassⅢ Grade A hospitals in Shandong Province were selected by convenient sampling. The nurses were investigated online by using the self-developed General Information Questionnaire, Premature Infant Posture Management Knowledge, Attitude and Practice Questionnaire for NICU Nurses and Premature Infant Posture Management Training Needs Questionnaire for NICU Nurses. Multiple linear regression was used to analyze the influencing factors of NICU nurses' knowledge, attitude and practice in the posture management of premature infants. A total of 207 questionnaires were distributed, and 201 valid questionnaires were recovered, with an effective recovery rate of 97.10% (201/207) .Results:Among 201 NICU nurses, the scores of premature infant posture management knowledge, attitude, practice and total score were (59.12±7.82) , (33.10±3.09) , (54.92±7.36) and (147.14±15.15) respectively. Multiple linear regression analysis results show that the nature of the working hospital, whether they received relevant training, and the importance of participating in relevant training were the influencing factors of NICU nurses' total score of knowledge, attitude and practice in the posture management of premature infants ( P<0.05) . 78.11% (157/201) of NICU nurses accepted the training of premature infant posture management, 98.01% (197/201) of NICU nurses were willing to accept the training of premature infant posture management, and 91.04% (183/201) of NICU nurses thought it was very important to participate in the training of premature infant posture management. NICU nurses believed that the main obstacle affecting the quality of posture management of premature infants was the lack of relevant knowledge. The most desired training content was the effect of different postures on premature infants. Conclusions:NICU nurses have a high level of knowledge, attitude and practice in posture management of premature infants. Managers should strengthen the training of NICU nurses in the posture management of premature infants, improve the ability of NICU nurses in the posture management of premature infants, and promote the improvement of the nursing quality of premature infants.

Licking behavior is important for water intake. The deep mesencephalic nucleus (DpMe) has been implicated in instinctive behaviors. However, whether the DpMe is involved in licking behavior and the precise neural circuit behind this behavior remains unknown. Here, we found that the activity of the DpMe decreased during water intake. Inhibition of vesicular glutamate transporter 2-positive (VGLUT2⁺) neurons in the DpMe resulted in increased water intake. Somatostatin-expressing (SST⁺), but not protein kinase C-δ-expressing (PKC-δ⁺), GABAergic neurons in the central amygdala (CeA) preferentially innervated DpMe VGLUT2⁺ neurons. The SST⁺ neurons in the CeA projecting to the DpMe were activated at the onset of licking behavior. Activation of these CeA SST⁺ GABAergic neurons, but not PKC-δ⁺ GABAergic neurons, projecting to the DpMe was sufficient to induce licking behavior and promote water intake. These findings redefine the roles of the DpMe and reveal a novel CeA^SST-DpMe^VGLUT2 circuit that regulates licking behavior and promotes water intake.

OBJECTIVE: To investigate the role of NOV/CCN3 in regulating the proliferation of mesenchymal stem cells (MSCs) and its regulatory mechanism and assess the value of CCN3 as a proliferative factor in bone tissue engineering. METHODS: Mouse embryonic fibroblasts (MEFs) were used as the MSC model, in which CCN3 expression was up-regulated and downregulated by transfection with the recombinant adenovirus vectors Ad-CCN3 and Ad-siCCN3, respectively. Flow cytometry was used to analyze the changes in cell cycle and apoptosis of the transfected cells. Western blotting was used to detect the expression levels of the proliferation indicators (PCNA, cyclin E, and cyclin B1) and the apoptosis indicators (Bax and Bcl-2) to assess the effect of modulation of CCN3 expression on MEF proliferation and apoptosis. CCN3 protein secretion by the cells was detected using ELISA. RT-qPCR and Western blotting were employed to analyze the changes in the expressions of Notch1, ligand DLL1, the downstream key proteins or genes (Hey1, P300, H3K9) and MAPK pathway-related proteins ERK1+2 and p-ERK1+2. RESULTS: Flow cytometry showed that compared with the control cells, MEFs transfected with Ad-CCN3 exhibited significantly increased cell proliferation index ( CONCLUSIONS CCN3 over-expression promotes the proliferation and inhibits apoptosis of MEFs possibly by inhibiting the classical Notch signaling pathway and activating the MAPK pathway
Animals ; Apoptosis ; Cell Cycle ; Cell Proliferation ; Fibroblasts ; Mice ; Nephroblastoma Overexpressed Protein

Objective:To investigate the clinicopathological characteristics and 18F-fluorodeoxyglucose (FDG) PET/CT imaging features of bronchopulmonary neuroendocrine tumors(BP-NETs) with different pathological subtypes. Methods:From January 2013 to May 2018, 280 patients (196 males, 84 females, median age 58 years) with BP-NETs proved by pathology in Henan Provincial People′s Hospital were retrospectively analyzed. Age, gender, smoking history, the location and size of tumor, Ki-67 positive index, thyroid transcription factor-1 (TTF-1), synaptophysin (Syn), chromogranin-A (CgA), CD56, maximum standardized uptake value (SUV max), lymph node metastasis and distant metastasis were compared among 4 pathological subtypes of BP-NETs, including typical carcinoid (TC), atypical carcinoid (AC), small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). One-way analysis of variance, χ2 test, Fisher exact test and Kruskal-Wallis rank sum test were used for data analysis. Results:There were significant differences in age, smoking history, tumor size and location, Ki-67 positive index, CgA, CD56, TTF-1, SUV max and TNM stage among TC( n=59), AC( n=21), SCLC( n=184) and LCNEC ( n=16) groups ( F values: 2.067, 3.358, H values: 17.749-22.351, all P<0.05). SCLC had the largest tumor size (5.5(3.0, 6.8) cm) and the highest proportion of central type (85.3%, 157/184), and were more prone to lymph node metastasis. LCNEC had the oldest age ((66±16) years), the largest proportion of smoking history (14/16) and peripheral type (12/16). CD56 in SCLC (95.7%, 176/184) and LCNEC(15/16) mostly showed positive expression, while the positive expression rates of CgA and TTF-1 were higher in TC and AC (96.6%(57/59), 93.2%(55/59) and 95.2%(20/21), 90.5%(19/21), respectively). The Ki-67 positive index and SUV max of the four subtypes were significantly different, with the highest in SCLC group and the lowest in TC group. Conclusion:Different pathological subtypes of BP-NETs manifest different clinicopathological features and imaging presentation on 18F-FDG PET/CT, which are useful for understanding their characteristics.

Objective:To explore the relationship between genotypes and phenotypes in hypertrophic cardiomyopathy(HCM) patients using whole exome sequencing(WES) and three-dimensional speckle-tracking echocardiography(3D-STE).Methods:Twenty patients with apical HCM(ApHCM) and 25 patients with non-apical HCM(non-ApHCM) from June 2018 to January 2019 in Zhongshan Hospital of Fudan University were enrolled. All subjects underwent venous blood sampling and WES. Regular two-dimensional echocardiography was performed to acquire the following parameters: interventricular septum thickness, left ventricular posterior wall thickness, left ventricular end diastolic diameter, left ventricular end systolic diameter, the maximum thickness of left ventricular walls and left ventricular ejection fraction(LVEF). Full volume images were collected and then off-time analyzed with 3D-STE to acquire global longitudinal strain(GLS), global circumferential strain(GCS), twist and torsion. The relationships between above parameters, genotypes and phenotypes of left ventricle were analyzed.Results:Mutations were found in 73% of HCM patients.The two most common genes MYBPC3 and MYH7 accounted for 18% and 15% of mutations respectively. KCNEc.79C>T(p.Arg27Cys) and PRKAG2c.905G>A (p.Arg302Gln) were detected in both ApHCM group and non-ApHCM group. In ApHCM group, 60% of patients carried genetic mutations, which was significantly lower than non-ApHCM group(84%)( P=0.041). Compared with non-ApHCM group, GLS in ApHCM group was significantly higher ( P=0.008). There was no statistical difference of GLS between patients with mutations and without mutations( P=0.068). GLS demonstrated a moderate correlation with morphologic types of HCM(ApHCM and non-ApHCM)( r=0.364, P=0.012). However, there was no correlation between GLS and the condition of mutations( r=0.269, P=0.062). Conclusions:The relationship between genetics and phenotypic expression of HCM appears to be complex and heterogeneous. There are marked differences in gene mutations and systolic functions between ApHCM and non-ApHCM. The value of GLS correlates with the shape of left ventricle but not with genotypes.

Objective: To investigate the regularity and clinical significance of abnormal bone uptake of ⁹⁹Tc^m-methylene bisphosphonate (MDP) in benign and malignant lesions. Methods: A retrospective analysis was performed on 266 patients (132 males, 134 females, age range: 8-85 years) with abnormal uptake of ⁹⁹Tc^m-MDP in extraosseous tissues from September 2015 to March 2018. The final diagnosis of abnormal uptake was made according to the histopathology, laboratory and related imaging examination (CT, MRI, ultrasound, SPECT/CT or PET/CT imaging) results within 2 weeks after ⁹⁹Tc^m-MDP imaging. Regularity of abnormal ⁹⁹Tc^m-MDP uptake was comprehensively analyzed. Differences between benign and malignant groups were compared by χ² test or Fisher exact test. Results: Abnormal ⁹⁹Tc^m-MDP uptake in extraosseous tissues in 232 patients (87.2%, 232/266) were confirmed as malignant lesions and those in 34 patients (12.8%, 34/266) were benign. There were no significant differences in gender (χ²=0.611, P>0.05), age (P=0.584), and location (P=0.118) between benign and malignant lesions, but the involvement was significantly different (χ²=19.515, P<0.05). There were significant differences between single focus and diffuse foci of single organ, diffuse foci of single organ and multiple foci groups (χ²=8.959, 19.325, both P<0.01). Conclusions The detection rate of malignancy among foci with abnormal ⁹⁹Tc^m-MDP uptake in extraosseous tissues is high, and the malignancy may relate with the involvement of foci. When extraosseous uptake is found, clinical information and related examination results should be comprehensively analyzed and the malignancy should be taken into account.