Objective:To analyze the effectiveness and interobserver agreement of the Parer five-tier, the National Institute of Child Health and Human Development (NICHD) three-tier, and the International Federation of Gynecology and Obstetrics (FIGO) three-tier electronic fetal monitoring (EFM) systems in identification of neonatal acidosis during labor.Methods:This retrospective study was conducted on full-term singleton cephalic deliveries with neonatal acidosis (umbilical artery blood gas pH≤7.1) and normal newborns (umbilical artery blood gas pH≥7.2) in the Nanjing Drum Tower Hospital, Nanjing University Medical School from January to December 2020. EFM tracings during the last 30-60 min before delivery were collected. Four obstetricians independently described the features of randomly sorted and coded EFM tracings. Another obstetrician categorized these tracings using the NICHD three-tier, FIGO three-tier, and Parer five-tier evaluation systems based on the features. All researchers were masked to the clinical characteristics and maternal and neonatal outcomes. The sensitivity and specificity for identifying neonatal acidosis, as well as the interobserver agreement, were analyzed for all three systems. Independent sample t-test, Chi-square (or Fisher's exact test) and Mann-Whitney U tests were used for statistical analysis. Inter-group comparisons of sensitivity and specificity between the three evaluation systems were assessed using McNemar's test. The Kappa statistic was used to analyze interobserver agreement. Results:This study included a total of 3 558 cases. After propensity score matching, there were 44 cases of neonatal acidosis and 78 control cases. There were no significant differences in parity, gestational weeks, modes of delivery, placental abruption, or analgesia rates between the two groups. The rates of instrumental vaginal delivery and neonatal intensive care unit (NICU) admission in the acidosis group were significantly higher than those in the control group [15.8% (7/44) vs. 2.6% (2/78), χ2=8.45, P=0.003; 31.8% (14/44) vs. 12.8% (10/78), χ2=8.45, P=0.004], while the umbilical artery blood pH and mean base excess were lower in the acidosis group than in the control group [7.04±0.07 vs. 7.30±0.05, t=4.98; (－12.40±3.32) vs. (－5.64±1.95) mmol/L, t=13.61; both P<0.001]. (2) Using the NICHD three-tier system, 95.5% (42/44) of the acidosis cases and 89.7% (70/78) of the control cases were classified as having category Ⅱ EFM tracings, indicating potential fetal acid-base imbalance; category Ⅲ EFM tracings were only observed in 4.5% (2/44) of the cases in the acidosis group. With the FIGO three-tier system, 81.8% (36/44) of the acidosis cases were categorized as having "pathological" tracings, and with the Parer five-tier system, 86.4% (38/44) of the acidosis cases were correctly classified into the "orange or red" risk zones that indicated acid-base imbalance. Among the control cases, there were 28.2% (22/78) with EFM tracings of "normal patterns" categorized by the FIGO three-tier system, and 41.0% (32/78) classified into the "green or blue" risk zones by the Parer five-tier system, which indicated good fetal conditions. None of the acidosis cases were misdiagnosed as being normal by the Parer five-tier system. (3) Compared with the NICHD three-tier system, both the FIGO three-tier and the Parer five-tier systems showed increased diagnostic sensitivity [4.5% (1.2%- 14.5%) vs. 81.8% (66.8%-89.4%) and 86.4% (71.8%-92.4%)], but decreased specificity [100.0% (95.3%- 100.0%) vs. 87.2% (78.0%-92.9%) and 84.6% (75.0%-91.0%)]. There was no statistically significant difference in the sensitivity or specificity between the FIGO three-tier and Parer five-tier systems for identifying neonatal acidosis ( P=0.727 and 0.791). (4) When reading the tracings of control cases, the total agreement rate for the NICHD three-tier system by different observers was as high as 94.2%, while the total agreement rates for the FIGO three-tier and Parer five-tier systems were 69.7% and 67.7%, respectively. In the interpretation of EFHR tracings for acidosis cases, the interobserver agreement for the Parer five-tier system was excellent [Kappa (95% CI): 0.87 (0.79-0.95)], while both the NICHD three-tier and FIGO three-tier systems showed good agreement [Kappa (95% CI): 0.77 (0.66-0.88) and 0.72 (0.60-0.84)]. Conclusions:The Parer five-tier and the FIGO three-tier systems have higher sensitivity in identifying neonatal acidosis than the NICHD three-tier system, and the Parer five-tier system achieves a higher negative predictive value and a greater agreement in the interpretation of pathological EFM patterns.

Hepatic stellate cells (HSCs) represent a significant component of hepatocellular carcinoma (HCC) microenvironments which play a critical role in tumor progression and drug resistance. Tumor-on-a-chip technology has provided a powerful in vitro platform to investigate the crosstalk between activated HSCs and HCC cells by mimicking physiological architecture with precise spatiotemporal control. Here we developed a tri-cell culture microfluidic chip to evaluate the impact of HSCs on HCC progression. On-chip analysis revealed activated HSCs contributed to endothelial invasion, HCC drug resistance and natural killer (NK) cell exhaustion. Cytokine array and RNA sequencing analysis were combined to indicate the iron-binding protein LIPOCALIN-2 (LCN-2) as a key factor in remodeling tumor microenvironments in the HCC-on-a-chip. LCN-2 targeted therapy demonstrated robust anti-tumor effects both in vitro 3D biomimetic chip and in vivo mouse model, including angiogenesis inhibition, sorafenib sensitivity promotion and NK-cell cytotoxicity enhancement. Taken together, the microfluidic platform exhibited obvious advantages in mimicking functional characteristics of tumor microenvironments and developing targeted therapies.

Objective:To extract the differentially expressed key genes of primary biliary cholangitis (PBC) using bioinformatics methods, so as to provide information for further study into the mechanism.Methods:The GSE119600 dataset was downloaded from the GEO database to obtain differentially expressed genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Protein-protein interaction (PPI) network reconstruction, Cytoscape software visualization, and core gene screening were performed. The area under the receiver operating characteristic curve (ROC AUC) was used to assess the diagnostic effectiveness of genes and plot the pROC software package. The x-Cell software was used to calculate the enrichment score of 34 immune cells in each sample. Finally, four key genes (PSMA4, PSMA1, PSMB1, and PSMA3) were selected. Blood samples were analyzed using the qPCR method.Results::A total of 373 immune-related differentially expressed genes were identified. Eight genes (PSMC6, PSMB2, PSMB1, PSMA3, PSMA4, PSMA1, PSMD7, and PSMB5) were screened from the 178 nodes and 596 edges as hub genes of the PPI network, which were significantly related to amino acid metabolism, hematopoietic stem cell differentiation, cell cycle, and immune processes. PSMA4, PSMA1, PSMB1, and PSMA3 were defined as immunological biomarkers for PBC with an AUC value of the ROC curve > 0.7. Immunoinfiltrating cell analysis showed that the proportion of eosinophils was significantly higher in PBC patients compared to the control group, whereas the proportion of CD4+ memory T cells, plasma cells, Th2 cells, and cDC cells was significantly lower in PBC patients than the control group. Plasma cells were associated with all four immunological biomarkers. Seven PBC patients and seven healthy subjects were selected for peripheral blood qPCR validation, which demonstrates that PSMB1, PSMA3, PSMA1, and PSMA4 levels were significantly lower in PBC patients than healthy subjects, with a statistically significant difference.Conclusion::Bioinformatics screened eight key genes, of which four were key immunological markers and may serve as a basis for clinical diagnosis and mechanism exploration.

Objective:To explore the application value of artificial intelligence (AI) model based on deep learning in breast nodules classification of Breast Imaging Reporting and Data System of ultrasound (BI-RADS-US).Methods:The ultrasound images of 2 426 breast nodules from 1 558 female patients with breast diseases at Beijing Tongren Hospital, Capital Medical University between December 2006 and December 2019 were collected . The image data sets were divided into training (63%), verification (7%), and test (30%) subsets for the construction of AI model. The diagnostic efficiencies of AI model, doctors' arbitration results and doctors' diagnosis with or without AI model assistance were analyzed by using receiver operating characteristic (ROC) curve. The Cohen weighted Kappa statistic was used to compare the consistency of BI-RADS-US classification among 5 ultrasound doctors' diagnosis with or without AI model assistance. And the changes of BI-RADS-US classification were analyzed before and after each doctor adopted AI model assistance.Results:The differences in diagnostic efficiencies of AI model, doctors' arbitration results and doctors' diagnosis with or without AI model assistance were statistically significant (all P > 0.05). The consistency among 5 ultrasound doctors was improved due to AI model assistance and Kappa value was increased from 0.433 (category 3), 0.600 (category 4a), 0.614 (category 4b), 0.570 (category 4c) and 0.495 (category 5) to 0.812, 0.704, 0.823, 0.690 and 0.509 (all P < 0.05), respectively. The upgrade and downgrade of BI-RADS-US classification occurred in 5 doctors after the classification of AI model assistance. Downgrade from category 4 to 3 in benign nodules of 56.6% (47/76) and upgrade from category 4 to 5 in malignant nodules of 69.4% (34/49) were mostly observed. Conclusions:AI-assisted BI-RADS-US classification can effectively improve the consistency of classification among the doctors without reducing the diagnostic efficiency. AI model shows clinical values in reducing unnecessary biopsy of partial benign lesions and increasing diagnostic accuracy of partial malignant lesions through the adjustment of breast nodule classification.

The diagnosis of food allergy in children is one hotspot attracting people′s attention in recent years.The incidence of it shows an increasing trend which exposes problems in the understanding of children′s food allergy in China, especially in the misdiagnosis and missed diagnosis.To further standardize the diagnosis and treatment of food allergy in children, based on the current domestic, foreign guidelines and relevant research evidence, the guideline recommends 16 clinical hot-button issues in the 4 aspects of diagnosis, treatment, prognosis, and prevention.Finally, a diagnosis flowchart has been formulated.The guideline aims to improve the standard diagnosis and treatment of food allergies in children in China.

Objective:To understand the current situation of nurses in 52 hospitals in China on mastery of knowledge about skin injury in the elderly based on the background of mixed-mode homogenization training.Methods:Using the convenient sampling method, a total of 1 067 nurses from 52 hospitals in China were selected as the research objects in January 2021. A self-designed questionnaire on knowledge of skin injury in the elderly was used to investigate the nurses through the questionnaire star and univariate analysis was used to analyze the influencing factors. A total of 1 067 questionnaires were distributed and 1 067 valid questionnaires were recovered, and the effective recovery rate was 100%.Results:The knowledge scores of pressure injury, incontinence-associated dermatitis, skin tear and xerosis cutis among 1067 nurses were (95.66±7.37) , (95.65±9.15) , (91.37±15.45) and (87.67±15.91) , respectively. The results of univariate analysis showed that hospital grade was the influencing factor of nurses' knowledge score of pressure injury, skin tear and incontinence-associated dermatitis ( P<0.05) , educational background was the influencing factor of nurses' knowledge score of skin tear ( P<0.05) , professional title was the influencing factor of nurses' knowledge scores of pressure injury, incontinence-associated dermatitis and xerosis cutis ( P<0.05) . Conclusions:Hospitals at all levels need to strengthen the theoretical and practical knowledge training for nurses on skin xerosis and skin tear in the elderly, especially for nurses with primary titles and lower education in grassroots hospitals.

OBJECTIVE: To explore the mechanism by which ginsenoside 20(S)-Rg3 upregulates the expression of tumor suppressor von Hippel-Lindau (VHL) gene in ovarian cancer cells. METHODS: Ovarian cancer cell line SKOV3 treated with 20(S)-Rg3 were examined for mRNA and protein levels of VHL, DNMT1, DNMT3A and DNMT3B by real-time PCR and Western blotting, respectively. The changes in VHL mRNA expression in SKOV3 cells in response to treatment with 5-Aza-CdR, a DNA methyltransferase inhibitor, were detected using real-time PCR. VHL gene promoter methylation was examined with methylation-specific PCR and VHL expression levels were determined with real-time PCR and Western blotting in non-treated or 20(S)-Rg3-treated SKOV3 cells and in 20(S)-Rg3-treated DNMT3A-overexpressing SKOV3 cells. VHL and DNMT3A protein levels were detected by immunohistochemistry in subcutaneous SKOV3 cell xenografts in nude mice. RESULTS: Treatment of SKOV3 cells with 20(S)-Rg3 significantly upregulated VHL and downregulated DNMT3A expressions at both the mRNA and protein levels ( CONCLUSIONS Ginsenoside 20(S)-Rg3 upregulates VHL expression in ovarian cancer cells by suppressing DNMT3A-mediated DNA methylation.
Animals ; Cell Line, Tumor ; DNA Methylation ; Female ; Gene Expression ; Ginsenosides/pharmacology* ; Humans ; Mice ; Mice, Nude ; Ovarian Neoplasms/genetics* ; Promoter Regions, Genetic ; Von Hippel-Lindau Tumor Suppressor Protein/genetics*

Objective: To investigate the serotype distribution and antimicrobial susceptibility pattern of Streptococcus pneumoniae (S. pneumoniae), Haemophilus influenzae (H. influenzae) and Moraxella catarrhalis (M. catarrhalis) isolates collected from nasopharyngeal swabs from Uygur children in Kashi. Methods: Nasopharyngeal swabs were collected from inpatient Uygur children aged from 1 month to 5 years with respiratory infections from the pediatric department, the First People's Hospital of Kashi, Xinjiang Uygur Autonomous Region. Antimicrobial susceptibilities of the isolates were determined with E-test and KB disk diffusion methods. The production of β-lactamase was detected for H. influenzae and M. catarrhalisisolates using nitrocefin disc method. Quellung test and latex agglutination test were adopted to identify serotypes of S. pneumoniae and H. influenzae isolates. Results: Forty-seven S. pneumoniae, 13 H. influenzae and 16 M. catarrhalis isolates were detected. All of the 47 S. pneumoniae isolates were sensitive to parenteral penicillin, amoxicillin-clavulanic acid, vancomycin and levofloxacin; the susceptibility rates to cefotaxime, imipenem and chloramphenicol were 94% (44/47), 89% (42/47), and 98% (46/47). The resistance rate to erythromycin was 74% (35/47). The most common serotype of S. pneumoniae was serotype 19A (10 strains, 21%). The coverage rate of 13-valent conjugate vaccine (PCV13) was 70% (33/47). None of the 13 H. influenzae isolates could be typed. They were highly susceptible to tested β-lactams antibiotics, except ampicillin. Only one H. influenzae isolate could produce β-lactamase, and two isolates were identified as β-lactamase-negative-ampicillin-resistant ones. The sixteen M. catarrhalis isolates were all positive in β-lactamase detection, but sensitive to amoxicillin-clavulanic acid, cephalosporins and meropenem. Conclusions In Kashi, Xinjiang Uygur Autonmous Region, S. pneumoniae isolates from Uygur children were highly sensitive to parenteral penicillin and other β-lactams antibiotics. H. influenzae isolates from Uygur children were highly susceptible to amoxicillin-clavulanic acid, cephalosporins and ciprofloxacin. All M. catarrhalis isolates from Uygur children could produce β-lactamase, but were sensitive to the enzyme inhibitors and cephalosporins.

Objective To observe value of high frequency ultrasound for inspection of T7-8 paravertebral space and adjacent structures.Methods Color Doppler ultrasonic diagnostic apparatus with linear array transducer (frequency 3-12 MHz) were used.Taking shoulder blade,ribs,thoracic spine and transverse process as anatomical marks,T7-8 paravertebral spaces of 30 normal adult (a total of 60 side) were examined.Ultrasonographic features of T7-8 paravertebral space and the adjacent structures were observed.Results T7-8 thoracic paravertebral showed as similar triangular shape with ultrasonography,interior solid homogeneously hypoechoic was noticed.Adjacent muscles of T7-8 paravertebral space included the trapezius,latissimus dorsi,spinalis,semispinalis,multifidus,rotatores and intercostal muscles.Color Doppler or power Doppler flow imaging could demonstrate posterior intercostal artery in the paravertebral space.Conclusion High frequency ultrasound can clearly show T7-8 paravertebral space and adjacent structures,thus providing ultrasonic references for clinical diagnosis and treatment of lesions of thoracic space and adjacent structures.

OBJECTIVE To assess the ultrasonographic features and clinical significance of the complications of the thyroglossal cysts. METHODS We retrospectively reviewed the ultrasonographic findings in 41 cases with complications of the thyroglossal cyst, which was confirmed surgically and pathologically. 43 cases with simple thyroglossal cyst consisted of the control group. The location, size, internal echo, internal septa, wall thickness, posterior acoustic feature, boundary, vascularity, and fistulas of the lesion were analyzed and compared with the control group. RESULTS Most of the inflammatory thyroglossal cyst showed thickening walls, indistinct boundaries, posterior echo enhancement, and peripheral vascularity on ultrasound images. There were significant differences of the thickness of the cyst wall, indistinct boundary, and peripheral vascularity between the two groups. CONCLUSION The characteristic findings of thyroglossal cyst with inflammation are thickened wall, indistinct boundary, and peripheral vascularities. Ultrasonography can be useful tool in determination of the appropriate time of the operation to reduce the recurrence rate.