Objective:Currently,traditional cervical cancer screening methods,such as high-risk human papillomavirus testing and liquid based cytology(LBC),still possess limitations.This study aims to identify new diagnostic biomarkers to achieve the goal of"precision screening"via exploring the clinical value of DNA methylation[ΔCtP:paired box gene 1(PAX1)and ΔCtJ:junctional adhesion molecule 3(JAM3)]detection in cervical exfoliated cells for the diagnosis of high-grade cervical lesions. Methods:A total of 136 patients who underwent gynecological examinations in the vaginal room of the Department of Gynecology at the Third Xiangya Hospital of Central South University from June 2021 to June 2022 were retrospectively studied.Among them,122 patients had non-high-grade cervical lesions,and 14 patients had high-grade cervical lesions.The variables included general information(age,body mass index,and menopause status),LBC,high-risk human papillomavirus,cervical tissue pathology,vaginal examination results,and the ΔCt values of JAM3 and PAX1 gene methylation.Logistic regression analysis was used to identify the factors affecting the diagnosis of high-grade cervical lesions,followed by correlation analysis and construction of a conditional inference tree model. Results:Logistic regression analysis showed that the methylation ΔCt values of PAX1 and JAM3 genes and LBC detection results were statistically significant between the high-grade cervical lesions group and the non-high-grade cervical lesions group(all P<0.05).Correlation analysis revealed a negative correlation between cervical pathological changes and ΔCtP(r=-0.36,P<0.001),ΔCtJ(r=-0.448,P<0.001),LBC(r=-0.305,P<0.001),or bacterial diversity(r=-0.183,P=0.037).The conditional inference tree showed that when ΔCtJ>10.13,all of patients had non-high-grade cervical lesions,while ΔCtP>6.22,the number of non-high-grade lesions accounted for 97.5%(117/120),and high-grade lesions accounted for only 2.5%(3/120).When ΔCtJ>8.61 and LBC were atypical squamous cell of undetermined significance or negative for intraepithelial lesions or malignancy(NILM),105(99.1%)patients were non-high-grade cervical lesions,only 1(0.9%)patient was high-grade lesion.When the results of LBC were high-grade lesions,only 9 patients'histopathological examination was the high-grade lesions and 3 non-high-grade lesions.When LBC indicated low-grade lesions,atypical squamous cell of undetermined significance,no intraepithelial lesions,and ΔCtP>6.22,117(97.5%)of patients'histopathological examination was the non-high-grade lesions. Conclusion:The JAM3/PAX1 gene methylation test can be used independently for the stratified diagnosis of high-grade/non-high-grade cervical lesions in women with high-risk human papillomavirus infection,independent of the cytological results of cervical excision.The JAM3/PAX1 gene methylation test can also be used in combination with LBC to make up for the shortcomings of low sensitivity of LBC.In addition,the application of methylation kit in large-scale cervical cancer screening in the future will be good to the detection of more patients with high-grade cervical lesions,and achieve early screening and early treatment for cervical lesions/cancer.

OBJECTIVES: Staphylococcus epidermidis (S. epidermidis) is a Gram-positive opportunistic pathogen that often causes hospital infections. With the abuse of antibiotics, the resistance of S. epidermidis gradually increases, and drug repurposing has become a research hotspot in the treating of refractory drug-resistant bacterial infections. This study aims to study the antimicrobial and antibiofilm effects of simeprevir, an antiviral hepatitis drug, on S. epidermidis in vitro. METHODS: The micro-dilution assay was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of simeprevir against S. epidermidis. Crystal violet staining assay was used to detect the biofilm inhibitory effect of simeprevir. The antimicrobial activity of simeprevir against S. epidermidis and its biofilm were explored by SYTO9/PI fluorescent staining. The combined effect between simeprevir and gentamycin was assessed by checkerboard assay and was confirmed by time-inhibition assay. RESULTS: Simeprevir showed significant antimicrobial effects against S. epidermidis type strains and clinical isolates with the MIC and MBC at 2-16 μg/mL and 4-32 μg/mL, respectively. The antimicrobial effects of simeprevir were confirmed by SYTO9/PI staining. Simeprevir at MIC could significantly inhibit and break the biofilm on cover slides. Similarly, simeprevir also significantly inhibit the biofilm formation on the surface of urine catheters either in TSB [from (0.700±0.020) to (0.050±0.004)] (t=54.03, P<0.001), or horse serum [from (1.00±0.02) to (0.13±0.01)] (t=82.78, P<0.001). Synergistic antimicrobial effect was found between simeprevir and gentamycin against S. epidermidis with the fractional inhibitory concentration index of 0.5. CONCLUSIONS Simeprevir shows antimicrobial effect and anti-biofilm activities against S. epidermidis.
Humans ; Simeprevir ; Antiviral Agents ; Anti-Bacterial Agents/pharmacology* ; Cross Infection ; Gentamicins

Purpose: This study aimed to develop a nomogram for predicting pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC) by integrating hematological biomarkers and clinicopathological characteristics. Materials and Methods: Between 2003 and 2017, 306 ESCC patients who underwent neoadjuvant CRT followed by esophagectomy were analyzed. Besides clinicopathological factors, hematological parameters before, during, and after CRT were collected. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for pCR. A nomogram model was built and internally validated. Results: Absolute lymphocyte count (ALC), lymphocyte to monocyte ratio, albumin, hemoglobin, white blood cell, neutrophil, and platelet count generally declined, whereas neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) increased significantly following neoadjuvant CRT. After surgery, 124 patients (40.5%) achieved a pCR. The pCR group demonstrated significantly more favorable survival than the non-pCR group. On multivariate analysis, significant factors associated with pCR included sex, chemotherapy regimen, post-CRT endoscopic finding, pre-CRT NLR, ALC nadir during CRT, and post-CRT PLR, which were incorporated into the prediction model. The nomogram indicated good accuracy in predicting pCR, with a C-index of 0.75 (95% confidence interval, 0.71 to 0.78). Conclusion Female, chemotherapy regimen of cisplatin/vinorelbine, negative post-CRT endoscopic finding, pre-CRT NLR (≤ 2.1), ALC nadir during CRT (> 0.35 ×109/L), and post-CRT PLR (≤ 83.0) were significantly associated with pCR in ESCC patients treated with neoadjuvant CRT. A nomogram incorporating hematological biomarkers to predict pCR was developed and internally validated, showing good predictive performance.

Objective:To explore the effect of preoperative visit with Child Life mode in the management of preschool children′s anxiety.Methods:A total of 80 cases of children of pre-school age who were operated from September 2018 to February 2019 were selected by cluster sampling method. The children from September to November 2018 who were given the traditional mode of preoperative visit were set as the control group. Children from December 2018 to February 2019 who were given preoperative visit with Child Life mode were set as the experimental group. The Modified Yale Perioperative Anxiety Scale (m-YPAS) scores, Induction Compliance Checklist (ICC) scores and Pediatric Anesthesia Emergence Delirium (PAED) scores were compared between the two groups at 4 different perioperative time points (6 hours after admission, waiting for surgery, induction of anesthesia, and 6 hours after surgery).Results:Totally three patients were suspended from the study due to surgery. A total of 77 children were studied, 38 in the experimental group and 39 in the control group. The score of m-YPAS in the experimental group was significantly lower than that of the control group(17.57±16.64 vs. 42.04±27.46, t value was 3.85, P<0.01) while waiting for surgery. The score of m-YPAS in the experimental group was significantly lower than control group (31.64±27.95 vs. 62.22±25.13, t value was 4.26, P<0.01) at the anesthesia induction. Compare with the control group, the score of m-YPAS in the experimental group showed no significant difference at both time of 6 hours after admission (18.19±17.83 vs.19.85±17.92, t value was 0.87, P>0.05) and 6 hours after surgery(35.61±15.70 vs. 41.81±17.97, t value was 1.37, P>0.05). Compare with the control group the score of ICC in the experimental group was significantly decreased (1.40±1.39 vs. 3.78±2.60, t value was 4.88, P<0.01) at the anesthesia induction. The score of PEAD in the experimental group and control group, there was no significant difference between the two groups (7.18±2.45 vs. 7.85±3.05, t value was 0.91, P>0.05). Conclusions:Compared with the traditional preoperative visit mode, the preoperative visit mode of Child Life can effectively relieve the anxiety of preschool children undergoing general anesthesia surgery while they are waiting for surgery and during anesthesia induction, and can improve the degree of cooperation during anesthesia induction.

Objective:To evaluate the ability of Sysmex urine automatic analyzer UF-5000 to detect renal tubular epithelial cells, and to explore the value of detection of renal tubular epithelial cells in renal tubular injury of diabetes mellitus.Methods:Case control study. 452 urine samples were collected from the third Xiangya Third Hospital of Central South University from October 2018 to April 2019 (252 in the control group, 113 in diabetes without renal injury group and 87 in diabetes with renal injury group). All samples were detected by both UF-5000 and microscopic examination, established reference range for normal population, then contrasted the coincidence rate and uniformity of the two methods, to evaluate the ability of urine automatic analyzer UF-5000 to detect renal tubular epithelial cells, and the diagnostic value of tubular epithelial cells for renal tubular injury in diabetic patients. All statistical analyses were performed using SPSS17.0, Kappa consistency analysis, ROC curve analysis, Kruskal-Wallis test and Chi-square test were used.Results:The reference range of renal tubular epithelial cells by Sysmex urine automatic analyzer UF-5000 is 0-1.7/μl. The results of the two methods were analyzed by Kappa consistency analysis. The Kappa value was 0.699, P>0.05, which meant highly consistent. ROC curve analysis showed when cut-off value was 1.7/μl. The sensitivity, specificity and area under ROC curve were 0.791, 0.817 and 0.861 respectively. The median of renal tubular epithelial cells was 0.4/μl, 2.0/μl and 2.3/μl in the healthy control group, the diabetes without renal injury group and the diabetes with renal injury group, respectively; the positive rate of renal tubular epithelial cells in the three groups were 2.78%, 56.64% and 75.86% respectively. Compared with the control group, the median and positive rate of renal tubular epithelial cells in the diabetes without renal injury group and the diabetes with renal injury group were significant different; there was also significant difference in the positive rate of renal tubular epithelial cells between the two groups. Conclusion:Compared with the control group, the positive rate of urine renal tubular epithelial cells indiabetes without renal injury group is significantly higher, which is helpful to detect renal tubular injury, to carry out early intervention and to prolong the time of progression to chronic kidney disease.

OBJECTIVE: To investigate the effect of osthole on the expression of amyloid precursor protein (APP) in Alzheimer's disease (AD) cell model and its mechanism. METHODS: The SH-SY5Y cell with over expression of APP was established by transfection by liposome 2000. The cells were treated with different concentrations of osthole, and the cell viability was determined by MTT and lactate dehydrogenase (LDH) assay. The differentially expressed miRNAs with and without osthole treatment were detected by miRNA array, and the target genes binding to the differentially expressed miRNAs were identified and verified by databases and Cytoscape. After the inhibitor of the differentially expressed miRNA was transduced into cells, the changes of APP and amyloid β (Aβ) protein were determined by immunofluorescence cytochemistry, and the mRNA expression of APP was determined by RT-PCR. RESULTS: The AD cell model with over expression of APP was established successfully. The results of MTT and LDH assay showed that osthole had a protective effect on cells and alleviated cell damage. miR-101a-3p was identified as the differentially expressed miRNA, which was binding to the 3'-UTR of APP. Compared with APP group, the expression of APP and Aβ protein and APP mRNA increased in the miR-101a-3p inhibitor group (all <0.01), while the expression of APP and Aβ protein and APP mRNA decreased in the cells with osthole treatment (all <0.01). CONCLUSIONS Osthole inhibits the expression of APP by up-regulating miR-101a-3p in AD cell model.
Alzheimer Disease ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; genetics ; Cell Line ; Coumarins ; pharmacology ; Gene Expression Regulation ; drug effects ; genetics ; Humans ; MicroRNAs ; genetics ; metabolism

Heated humidified high flow nasal cannula oxygen therapy (HFNC) has the characteristics of improving the work of breathing,creating the effect of positive end-expiratory pressure,being setted up easily,well tolerated by patients and high safety.At present,it has been widely used in neonatal respiratory support,but lack of its extensive use and research in infants and children.HFNC is suitable for use in infants with viral bronchiolitis,pneumonia,asthma,ARDS,and postextubation respiratory support from the aspect of the mechanism of action of HFNC and the pediatric physiology.HFNC should be the preferred mode of conventional oxygen therapy in pediatrics.

Objective To explore the diagnostic and score value of ultrasound on hemophiliac arthropathy referring to MRI on the diagnosis and score of hemophiliac arthropathy Methods The ultrasound and MRI examinations were performed on 42 joints of 42 hemophilia patients 14 knees 14 ankles and 14 elbows The consistency of ultrasound and magnetic resonance imaging in the detection and score of joint diseases was compared Finally inter-and intra-observer agreement of ultrasound scoring system were tested Results The consistency of ultrasound and magnetic resonance imaging was excellent κ=0 763-0 896 P < 0 001 in the detection of early soft tissue lesions effusion or hemarthrosis synovial hypertrophy hemosiderin excellent κ=0 793 P <0 001 in the detection of cartilage loss poor κ=0 133 P = 0 132 in the detection of erosions and poor κ= 0 100 P = 0 137 in the detection of subchondral cysts The consistency of ultrasound and magnetic resonance imaging was good to excellentκ=0 684-0 833 P < 0 001 in the score of early soft tissue lesions effusion or hemarthrosis synovial hypertrophy and hemosiderin and poor to good κ=0 145 -0 635 P <0 001 in the score of advanced osteochondral lesions cartilage loss and bone erosions The inter-observer agreement was good to excellent κ=0 676-0 870 P <0 001 for early soft tissue lesions and moderate to excellent κ=0 421- 0 75 1 P < 0 001 for advanced osteochondral lesions The intra-observer agreement was good to excellent κ=0 705-0 885 P <0 001 for early soft tissue lesions and moderate to good κ=0 532 -0 732 P <0 001 for advanced osteochondral lesions Conclusions Ultrasound plays an important role in detecting early soft tissue changes effusion or hemarthrosis synovial hypertrophy hemosiderin and cartilage loss which helps follow-up and guide clinical treatment.

Objective To analyze the status and the distribution of causes of injuries as well as disease burden in children under 5 years old in Sichuan Province.Methods The death information cards of children who died because of injuries in Sichuan Province in 2012 were analyzed,and the years of potential life lost and working years of potential life lost were calculated to evaluate the disease burden.Results 22.87％ (1 502/6 567) of children lost their lives because of injuries,the mortality of injury was 4.13‰,63.45％ of children died at the age between l and 4,and most of the children died at home or on the road; The top 3 causes of children death of injuries below 5 years old were drowning,accidental suffocation and traffic accidents.The years of potential life lost and working years of potential life lost were 73.05 years and 58.30 years.Conclusion Injury is one of the most mainly risk factor of health and life of children,the government should further prevent and control children injuries.

Objective To formulate a five-level pediatric emergency triage standard and evaluate the efficacy and reliability of it in determining severity of emergency pediatric patients.Methods According to the assessment methods in Pediatric Advanced Life Support recommended by American Heart Association and American Academy of Pediatrics,we formulated a five-level pediatric emergency triage standard based on the situation of our hospital and analyzed the data one year before and after the application of it.Results Before and after the application of the triage standard,the average satisfaction rate of emergency patients were (81.28 ± 3.97) ％ and (94.13 ± 4.62) ％,and there was significant difference (P ＜ 0.01) ; the proportion of whom became worse during waiting time were 1.83％ (628/34275) and 0.04％ (16/36 187),and there was significant difference (P ＜0.01) ;the average waiting time of emergency admission patients were (12.71 ± 2.32) min and (3.34 ± 1.95) min,and there was significant difference (P ＜0.01) ;the misjudgment rate of severity were 3.78％ (1 296/34 275) and 0.57％ (205/36 187),and there was significant difference (P ＜ 0.05).Conclusion The five-level triage standard is objective,easy to master,and suitable for pediatric triage.It can quickly sort out critical cases from emergency pediatric patients,which can improve the effectiveness of emergency service,make use of medical resources rationally and somewhat solve the problem of overcrowding.