Objective To explore the value of preoperative detection of soluble fragments of cytokeratin-19 (CYFRA21-1), carcinoembryonic antigen (CEA), and postoperative detection of nuclear proliferation associated antigen Ki67 in prognostic evaluation of non-small cell lung cancer patients. Methods The clinicopathological data and follow-up results of patients with non-small cell lung cancer treated in the Department of Thoracic Surgery of the First Affiliated Hospital of Xiamen University in 2017 were collected. CYFRA21-1>3.39 ng/mL was defined as positive, and CEA>5 ng/mL was defined as positive. The receiver operating characteristic curve (ROC curve) of Ki67 expression level was drawn. The maximum area under the curve (AUC) was the cutoff value of Ki67 expression level, and the Ki67 expression level greater than its cutoff value was defined as positive. Cox regression analysis was used to determine the independent risk factors for poor prognosis in patients with non-small cell lung cancer. Results Finally 248 patients were collected, including 125 males and 123 females, with a median age of 61 years (ranging from 30 to 81 years) at the time of surgery. Univariate analysis showed that positive CYFRA21-1, high expression of Ki67, positive CEA, age≥60 years at operation, distant metastasis, lymph node metastasis, maximum tumor diameter>3 cm, and TNM stage Ⅲ were associated with poor prognosis in patients with non-small cell lung cancer. When combined detection of preoperative tumor markers and postoperative Ki67, the prognosis of all negative patients was the best, and that of all positive patients was the worst. Cox regression analysis showed that positive CEA+positive CYFRA21-1+high expression of Ki67 was an independent risk factor for poor prognosis in patients with non-small cell lung cancer (P<0.05). Conclusion The combined detection of preoperative serum CYFRA21-1, CEA, and postoperative Ki67 has important value in evaluating the prognosis of non-small cell lung cancer patients.

Objective:To screen the main characteristic variables affecting the incidence of cardiovascular and cerebrovascular diseases,and to construct the Bayesian network model of cardiovascular and cerebrovascular disease incidence risk based on the top 10 characteristic variables,and to provide the reference for predicting the risk of cardiovascular and cerebrovascular disease incidence.Methods:From the UK Biobank Database,315 896 participants and related variables were included.The feature selection was performed by categorical boosting(CatBoost)algorithm,and the participants were randomly divided into training set and test set in the ratio of 7∶3.A Bayesian network model was constructed based on the max-min hill-climbing(MMHC)algorithm.Results:The prevalence of cardiovascular and cerebrovascular diseases in this study was 28.8％.The top 10 variables selected by the CatBoost algorithm were age,body mass index(BMI),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),the triglyceride-glucose(TyG)index,family history,apolipoprotein A/B ratio,high-density lipoprotein cholesterol(HDL-C),smoking status,and gender.The area under the receiver operating characteristic(ROC)curve(AUC)for the CatBoost training set model was 0.770,and the model accuracy was 0.764;the AUC of validation set model was 0.759 and the model accuracy was 0.763.The clinical efficacy analysis results showed that the threshold range for the training set was 0.06-0.85 and the threshold range for the validation set was 0.09-0.81.The Bayesian network model analysis results indicated that age,gender,smoking status,family history,BMI,and apolipoprotein A/B ratio were directly related to the incidence of cardiovascular and cerebrovascular diseases and they were the significant risk factors.TyG index,HDL-C,LDL-C,and TC indirectly affect the risk of cardiovascular and cerebrovascular diseases through their impact on BMI and apolipoprotein A/B ratio.Conclusion:Controlling BMI,apolipoprotein A/B ratio,and smoking behavior can reduce the incidence risk of cardiovascular and cerebrovascular diseases.The Bayesian network model can be used to predict the risk of cardiovascular and cerebrovascular disease incidence.

BACKGROUND: Implantation of bone marrow mesenchymal stem cells (BMSCs) is a potential alternative for promoting bone defects healing or osseointegration in osteoporosis. However, the reactive oxygen species (ROS) accumulated and excessive inflammation in the osteoporotic microenvironment could weaken the self-replication and multi-directional differentiation of transplanted BMSCs. METHODS: In this study, to improve the hostile microenvironment in osteoporosis, Poloxamer 407 and hyaluronic acid (HA) was crosslinked to synthetize a thermos-responsive and injectable hydrogel to load MnO2 nanoparticles as a protective carrier (MnO2 @Pol/HA hydrogel) for delivering BMSCs. RESULTS: The resulting MnO2 @Pol/HA hydrogel processed excellent biocompatibility and durable retention time, and can eliminate accumulated ROS effectively, thereby protecting BMSCs from ROS-mediated inhibition of cell viability, including survival, proliferation, and osteogenic differentiation. In osteoporotic bone defects, implanting of this BMSCs incorporated MnO2 @Pol/HA hydrogel significantly eliminated ROS level in bone marrow and bone tissue, induced macrophages polarization from M1 to M2 phenotype, decreased the expression of pro-inflammatory cytokines (e.g., TNFa, IL-1b, and IL-6) and osteogenic related factors (e.g., TGF-b and PDGF). CONCLUSION This hydrogel-based BMSCs protected delivery strategy indicated better bone repair effect than BMSCs delivering or MnO2 @Pol/HA hydrogel implantation singly, which providing a potential alternative strategy for enhancing osteoporotic bone defects healing.

Objective: To explore the relationship and gender difference between maternal adverse childhood experiences (ACEs) with emotional and behavioral problems (EBPs) in preschool children, and to provide a reference to promote emotional and behavioral problems among preschool children. Methods: Using the method of stratified cluster sampling, 9 647 children from kindergartens in three cities of Anhui Province were selected in June 2021. Maternal adverse childhood experiences were investigated with the WHO Adverse Childhood Experiences International Questionnaire(ACEs-IQ), preschool children s emotional and behavioral problems were investigated with Strengths and Difficulties Questionnaire. Results: The detection rate of abnormal emotional behavior was 17.4%, emotional symptoms 16.3%, conduct problems 18.3%, hyperactivity 22.7%, peer problems 34.2%, prosocial behaviors 18.5%. Multivariate Logistic regression analysis showed that maternal adverse childhood experiences were positively associated with the risk of emotional and behavioral problems ( OR =1.51-2.97, P <0.01). Maternal cumulative adverse childhood experiences were also positively associated with the risk of emotional and behavioral problems( OR =3.13-9.61, P <0.01). The association of maternal emotional abuse, physical abuse and community violence with peer problems were stronger in boys than that of girls ( ROR =1.25, 1.26, 1.41, P <0.05). Conclusion The findings suggest maternal adverse childhood experiences were associated with emotional behavior problems among preschool children. Focusing on the maternal adverse childhood experiences is crucial for the prevention and control of childhood emotional and behavioral problems.

Objective:To evaluate the clinical value of 18F-FDG PET/CT findings in patients with T1-2 lung adenocarcinoma spread through air spaces (STAS). Methods:From June 2018 to June 2020, a total of 80 patients (36 males, 44 females; age: 19-84 (59.9±11.8) years) with surgically and pathologically confirmed T1-2 lung adenocarcinomas in Jiangmen Central Hospital were enrolled retrospectively. All patients underwent 18F-FDG PET/CT examination preoperatively and were divided into STAS positive and negative groups according to the histopathological diagnosis. Independent-sample t test, Mann-Whitney U test, χ2 test and Fisher exact test were used to analyze differences of gender, age, tumor biomarker, SUV max, SUV mean, features showed on high resolution CT (HRCT; including diameter, lesion location, morphology, density, lobulated sharp, spiculated sign, vacuole sign, air bronchgram sign, pleural traction and para-emphysema), and pathologic findings (micropapillary pattern, lymphvascular inversion, pleural inversion and lymph node metastasis) between the two groups, and then multivariate logistic regression was performed. The ROC curve was employed to evaluate the predictive value of parameters for STAS of T1-2 lung adenocarcinomas. Results:Among the 80 patients with T1-2 lung adenocarcinomas, 12 (15.0%) were STAS positive and 68 (85.0%) were STAS negative. Significant differences were shown in SUV max, SUV mean, micropapillary pattern, lymphvascular inversion and lymph node metastasis between the two groups ( z values: -2.60, -2.17; χ2 values: 29.56, 9.28, 17.40, P<0.001 or P<0.05). SUV max (odds ratio ( OR): 1.348 (95% CI: 1.071-1.695), P=0.011), micropapillary pattern ( OR=47.444 (95% CI: 4.592-490.214), P=0.001) and lymph node metastasis ( OR=8.201 (95% CI: 1.129-59.576), P=0.038) were independent risk factors for STAS positive in multivariation logistic regression analysis. The optimum cut-off value for SUV max was 3.85 in the ROC analysis with the AUC of 0.737 (95% CI: 0.614-0.859), the sensitivity of 11/12, the specificity of 55.9%(38/68) and the accuracy of 61.2%(49/80). The AUC of the SUV max combined with micropapillary pattern and lymph node metastasis was 0.945 (95% CI: 0.892-0.999) with the sensitivity of 11/12, the specificity of 88.2%(60/68) and the accuracy of 88.7%(71/80). Conclusions:The PET/CT characteristics may be useful in differentiating STAS status among patients with T1-2 lung adenocarcinoma. SUV max >3.85, pathological papillary pattern and lymph node metastasis are independent risk factors to predict STAS.

Objective:To investigate the effect of different ischemic preconditioning (IPC) modes on ischemia-reperfusion (IR) injury of skeletal muscle in rats.Methods:Forty male SD rats were selected to construct the model of IR injury of skeletal muscle by clamping one side of the femoral artery. In the IPC mode, the right femoral artery was clipped for 10 minutes, and reperfusion ensued for 10 minutes after the release of artery clamp. Such preconditioning procedure was repeated 3 times. The rats were divided into conventional IR group, IPC immediate group, IPC24-hour group, IPC48-hour group and sham operation group according to the random number table method, with 8 rats in each group.In conventional IR group, the right femoral artery was clipped for 3 hours and then the artery clamp was released to allow reperfusion for 3 hours. In IPC immediate group, the same treatment as conventional IR group was performed immediately after preconditioning. In IPC24-hour group, the rats received skin suturing after preconditioning and then fed in a cage for 24 hours before the same treatment as conventional IR group. In IPC48-hour group, the rats received skin suturing after preconditioning and then fed in a cage for 48 hours before the same treatment as conventional IR group. In sham operation group, the right femoral artery was bluntly separated but not clipped. At the end of reperfusion, the tibialis anterior muscle tissue, gastrocnemius muscle tissue and serum were collected. The ratio of wet weight to dry weight (W/D) of the tibialis anterior muscle tissue was calculated to evaluate tissue edema. After HE staining, histopathological changes of gastrocnemius muscle were observed and the injury severity of gastrocnemius tissue was scored. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and malondialdehyde (MDA) were determined by ELISA. Expressions of hypoxia receptor (EGLN1) and hypoxia-inducible factor-1α (HIF-1α) in the gastrocnemius tissue were detected by real-time fluorescence quantitative PCR (qRT-PCR).Results:The degree of tissue edema was reduced under different IPC modes when compared with conventional IR group (all P<0.01). The W/D in conventional IR group, IPC immediate group, IPC24-hour group and IPC48-hour group were 6.05±0.19, 5.70±0.12, 5.25±0.13 and 5.50±0.08, higher than 3.80±0.08 in sham operation group (all P<0.01). IPC24-hour group had the least degree of edema when compared with IPC immediate group and IPC48-hour group ( P<0.05 or 0.01). The muscle fibers in sham operation group were neatly arranged with clear structure, and the muscle fibers in other groups showed different degrees of injury and inflammatory infiltration. The total scores for tissue injury severity in IPC immediate group, IPC24-hour group and IPC48-hour group were (8.15±0.15)points, (6.15±0.38)points and (6.90±0.19)points, lower than (9.60±0.50)points in conventional IR group and higher than (0.16±0.16)points in sham operation group (all P<0.01). The total scores for tissue injury severity in IPC24-hour group and IPC48-hour group were not significantly different ( P>0.05), but both decreased when compared with IPC immediate group ( P<0.05 or 0.01). ELISA showed that the levels of TNF-α, IL-1β and MDA under different IPC modes were higher than those in sham operation group (all P<0.01), and the order from high to low was conventional IR group, IPC immediate group, IPC48-hour group, IPC24-hour group and sham operation group. Levels of IL-1β, TNF-α and MDA in IPC24-hour group were decreased when compared with IPC immediate group and IPC48-hour group (all P<0.05). qRT-PCR showed that the expression of EGLN1 mRNA from high to low was conventional IR group, IPC48-hour group, sham operation group, IPC immediate group and IPC24-hour group and that the expression of EGLN1 mRNA in IPC24-hour group decreased when compared with conventional IR group, IPC immediate group and IPC48-hour group (all P<0.01). The expression of HIF-1α mRNA increased under different IPC modes when compared with sham operation group (all P<0.01), and the order from high to low was IPC24-hour group, IPC immediate group, IPC48-hour group, conventional IR group and sham operation group. The expression of HIF-1α mRNA in IPC24-hour group increased when compared with conventional IR group, IPC immediate group and IPC48-hour group ( P<0.05 or 0.01), but there was no significant difference between IPC immediate group and IPC48-hour group ( P>0.05). Conclusions:Different ischemic preconditioning modes can reduce IR injury of skeletal muscle in rats by reducing tissue edema, inflammatory symptoms and oxidative stress response, among which reperfusion 24 hours after IPC has the best effect on IR injury. EGLN1 and HIF-1α may be involved in IPC to alleviate IR injury of skeletal muscle in rats.

Objective:To preliminarily analyze the expression of angiotensin-converting enzyme 2 (ACE2) and to investigate its potential regulatory mechanism in chronic rhinosinusitis with nasal polyps (CRSwNP).Methods:Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from February 2020 to May 2021 were selected, including 17 males and 6 females, aging from 23 to 66 years old. Expression of ACE2 was evaluated via immunohistochemical staining in controls with non-chronic rhinosinusitis, non-eosinophilic CRSwNP (non-ECRSwNP), and eosinophilic CRSwNP (ECRSwNP) tissue, respectively. Correlations between ACE2 and the indicated Th1/Th2-related cytokines (IFN-γ, IL-4, IL-5, IL-13, IL-25, IL-33, TSLP and periostin) were analyzed based on GSE72713 dataset. Protein-protein interaction (PPI) network was constructed via string database, immune infiltration of GSE72713 dataset was evaluated using cibersort algorithm. ACE2 was comprehensively analyzed by microRNA regulatory network, gene set enrichment analysis (GSEA) and pharmacological analysis. Statistical analysis was performed using GraphPad 7.0 and SPSS 20.0 software.Results:ACE2 was up-regulated in non-ECRSwNP compared with ECRSwNP. Microarray analysis showed that ACE2 was positively correlated with IFN-γ while inversely correlated with IL-5, IL-13 and periostin significantly. Analysis of immune infiltration suggested that ACE2 expression correlated positively with the number of M1 macrophage while negatively with M2 macrophage. GSEA demonstrated that interferon-related signaling pathways were up-regulated in non-ECRSwNP, and miRNA-200B/miRNA-200C/miRNA-429 pathways targeting ACE2 were enriched in ECRSwNP. Results of pharmacological analysis indicated that ampicillin was able to promote the expression of ACE2 whereas acetaminophen could down regulated the expression of ACE2.Conclusion:Expression pattern of ACE2 is varied in non-ECRSwNP and ECRSwNP, which may be related to the different infiltration of indicated cytokines and different regulatory pathways of miRNA.

Objective To investigate the influence of nonalcoholic fatty liver disease (NAFLD) on the antiviral response of patients with chronic hepatitis B (CHB), and to provide a reference for clinical treatment of such patients. Methods A total of 187 patients who attended Shenzhen Third People's Hospital from January 2011 to December 2017 were enrolled and divided into CHB group with 43 patients, NAFLD group with 41 patients, and CHB+NAFLD group with 103 patients. Related indices were measured at enrollment different time points of follow-up, including body height, body weight, alanine aminotransferase (ALT), aspartate aminotransferase, four blood lipid parameters, four indicators of liver fibrosis, aspartate aminotransferase-to-platelet ratio index, HBsAg, HBeAg, anti-HBe, and HBV DNA quantification, and the CHB patients and the CHB+NAFLD patients receiving antiviral therapy were compared in terms of treatment outcome at weeks 12, 24, 48, 72, and 96 of antiviral therapy. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Wilcoxon rank-sum test was used for comparison between two groups; the chi-square test was used for comparison of categorical data between groups. Results Compared with the NAFLD group at baseline, the CHB group and the CHB+NAFLD group had significantly lower platelet count, ALT, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase, and right lobe of liver oblique diameter (all P < 0.05), and compared with the CHB group, the CHB+NAFLD group had significantly higher body mass index, total cholesterol, and triglyceride and a significantly lower spleen thickness (all P < 0.05), while there were no significant differences in the other indicators between the two groups at baseline (all P > 0.05). At week 12 of antiviral therapy, there were no significant differences in liver fibrosis markers and inflammatory indices between the CHB group and the CHB+NAFLD group (all P > 0.05); compared with the CHB+NAFLD group at weeks 24 and 48, the CHB group had significantly greater reductions in ALT ( Z =-2.128 and -3.055, both P < 0.05) and GGT ( Z =-2.025 and -1.631, both P < 0.05); at week 48, the CHB group and the CHB+NAFLD group had a significant reduction in HBV DNA ( Z =-6.445 and -4.415, both P < 0.001), and the CHB group had a significantly greater reduction. The CHB+NAFLD group had a significantly lower HBV DNA clearance rate than the CHB group at different time points of antiviral therapy ( χ 2 =14.237, 13.961, 15.226, 10.462, and 13.030, all P < 0.05). At week 48 of antiviral therapy, the CHB+NAFLD group had a significantly lower HBeAg clearance rate than the CHB group ( χ 2 =5.309, P =0.021), while there was no significant difference between the two groups at week 96 ( χ 2 =0.117, P =0.732). At weeks 24, 48, 72, and 96 of antiviral therapy, the CHB+NAFLD group had a significantly lower ALT normalization rate than the CHB group ( χ 2 =12.049, 5.287, 11.407, and 11.375, all P < 0.05). Conclusion NAFLD reduces the antiviral response of CHB patients and prolongs the duration of antiviral therapy.

Objective:To investigate the application value of new urinary biomarkers insulin-like growth factor binding protein 7 (IGFBP7) and tissue matrix metalloproteinase inhibitor-2 (TIMP-2) in acute kidney injury with decompensated hepatitis B virus-related liver cirrhosis.Methods:45 newly hospitalized cases with decompensated hepatitis B virus-related liver cirrhosis were selected. Among them, 19 cases were combined with AKI on admission (cirrhosis-AKI group), 26 cases without AKI (cirrhosis-non-AKI group), and 12 healthy cases (normal control group). First-morning urine samples were collected and IGFBP7 and TIMP-2 were detected by enzyme-linked immunosorbent assay (ELISA). Urinary IGFBP7 and serum creatinine (SCr) were dynamically monitored after hospitalization in cirrhosis-non-AKI group. Normally distributed measurement data were compared by t-test, and non-normally distributed measurement data were compared by rank sum test. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic accuracy of the indicators.Results:Urinary IGFBP7, IGFBP7 with TIMP-2 (IGFBP7×TIMP-2) in cirrhosis-AKI group ( n = 19) were equally higher than that of the cirrhosis-non-AKI group ( P < 0.05). Urinary IGFBP7, TIMP-2 and IGFBP7×TIMP-2 in cirrhosis-AKI group or cirrhosis-non-AKI group were significantly higher than those of the normal control group ( P < 0.01). The AUC of urinary IGFBP7 and urinary IGFBP7×TIMP-2 for diagnosis of AKI were 0.703 (95% CI 0.547-0.860) and 0.700 (95% CI 0.541-0.859), respectively. In the liver cirrhosis-non-AKI group ( n = 26), 5 cases of AKI were newly diagnosed according to the changes in SCr during hospitalization (progressive group). Urinary IGFBP7 was significantly increased 2 days before the diagnosis of AKI. The concentration of urinary IGFBP7 at admission in the progressive group ( n = 5) was higher than that of the non-progressive group ( n = 21) ( P < 0.05). Conclusion:Urinary IGFBP7 and TIMP-2 concentrations were significantly increased in patients with decompensated hepatitis B virus-related liver cirrhosis. When AKI occurred, urinary IGFBP7 and IGFBP7×TIMP-2 was further increased. Urinary IGFBP7 is valuable for early AKI diagnosis, and may play a role in predicting AKI occurrence.

With the rapid development and adaptation of high-throughput sequencing in clinical settings, application of exome sequencing (ES) has been gradually expanded from pediatric to prenatal diagnosis in recent years. There is an urgent need to establish criteria for clinical grade ES in order to facilitate such a complex testing. The standardization of pre- and post-test consultation, quality control for sample processing process and validation of bioinformatics data analysis, and more importantly data interpretation and reporting, as well as appropriate reporting scope, is of great importance for health care stakeholders. To achieve this, a committee composed of a wide range of healthcare professionals has proposed an ES standard for prenatal diagnosis. This has provided expert opinion on the genetic counseling and reporting standards of prenatal ES for the purpose of applying ES technology in prenatal setting.