Objective: To investigate the changes in oropharyngeal airway parameters and hyoid position in skeletal ClassⅡ adult female patients with different vertical skeletal types who were treated with maxillary anterior teeth retraction with maximum anchorage, and to provide a reference for orthodontic clinical diagnosis and treatment. Methods: This study was reviewed and approved by the Medical Ethics Committee, and informed consent was obtained from patients. Sixty adult female patients with skeletal ClassⅡ were selected and divided into a skeletal ClassⅡ normodivergent group and a skeletal ClassⅡ hyperdivergent group based on the patients’ mandibular plane angle. In both groups, the bilateral maxillary first premolars were extracted and the maxillary anterior teeth were retracted with maximum anchorage. Cone beam CT(CBCT) images were collected before and after treatment, and three-dimensional measurement software was used to analyze oropharyngeal airway-related parameters. Results: After retraction of the maxillary anterior teeth with maximum anchorage, the 10 parameters related to the oropharyngeal airway did not exhibit statistically significant differences in the normodivergent group (P>0.05), but the perpendicular distance from the highest point of the hyoid bone to the vertical line passing through the sella (H-X) value decreased (P<0.001). In the hyperdivergent group, the oropharyngeal area at the level of the epiglottis tip (OPA-E), anterior-posterior diameters of the oropharynx at the level of the epiglottis tip (E-AP), most constricted axial area of the oropharynx (OPA-MCA), and anterior-posterior diameters of MCA area of the oropharynx (MCA-AP) decreased after treatment (P<0.001). In addition, the oropharyngeal volume (OPV) decreased after treatment (P<0.05), and the perpendicular distance from the highest point of the hyoid bone to the horizontal line passing through the sella (H-Y) and the highest point of the hyoid bone to the epiglottis base (H-Eb) values increased after treatment (P<0.05). Conclusion After retraction of the maxillary anterior teeth with maximum anchorage, there is no change in the oropharyngeal airway in skeletal ClassⅡ normodivergent female adult patients, while skeletal ClassⅡhyperdivergent female adult patients have a risk of reduction in the oropharyngeal airway after maximuim anchorage retraction of the maxillary anterior teeth.

AIM:To investigate the expression of centromere protein-H(CENP-H)in adrenocortical carcino-ma(ACC)and its relationship with disease progression and prognosis,and to explore the impact of CENP-H gene knock-down on the viability and migration of ACC cells.METHODS:The mRNA expression level of CENP-H in 76 ACC pa-tients and 128 healthy controls,and its correlations with tumor stages and prognosis were analyzed by GEPIA2 database.The mRNA expression of CENP-H in different stages of ACC and its correlation with disease prognosis were further ana-lyzed by ULCAN database.The protein expression of CENP-H was examined by immunohistochemical staining of paraffin-embedded ACC and normal adrenal gland specimens.Knockdown of CENP-H by siRNA(siCENP-H)was performed in human ACC cell line H295R.The viabilty of H295R cells transfected with siCENP-H or siNC was measured by CCK-8 as-say,the cell migration was detected by wound-healing assay,and the protein levels of CENP-H,p-ERK1/2,t-ERK1/2,p-P38,t-P38,p-JNK1/2 and t-JNK1/2 were detected by Western blot.RESULTS:The mRNA level of CENP-H was signifi-cantly higher in ACC than that in normal controls,and was correlated with tumor stages and prognosis.The protein level of CENP-H was significantly higher in ACC specimens than that in normal adrenal gland.Knockdown of CENP-H in H295R cells resulted in decreased cell viability and migration.The protein levels of p-P38 and p-JNK1/2 were decreased in si-CENP-H group.CONCLUSION:CENP-H is highly expressed in ACC,and is correlated with tumor stages and poor prognosis.Knockdown of CENP-H can inhibit the viability and migration of ACC cells,and its mechanism may related to inactivation of P38 and JNK signaling pathways.

OBJECTIVE To establish a mouse model of diabetes mellitus(DM)combined with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection to investigate the important pathophysiological changes in the development of DM combined with SARS-CoV-2 infection.METHODS Wild-type(WT)mice and transgenic mice expressing the human angiotensin-converting enzyme 2 receptor driven by the cytokeratin-18 gene promoter(K18-hACE2)were randomly divided into the control group,DM group,SARS-CoV-2 spike protein(S)infection group and DM combined with S protein infection group,with 10 to 12 mice in each group.All the mice were induced by 10 weeks of high-fat diet combined with 40 mg·kg-1 streptozotocin(STZ)for 3 days by ip,except those in the control group or S protein infection group.The control group was given the same volume of 0.1 mol·L-1 sodium citrate buffer.Mice in the S protein infection group and DM+S protein infection group were additionally given 50 μL mixture of 15 μg SARS-CoV-2 spike protein and 1 g·L-1 polyinosinic-polycytidylic acid(poly[I:C])via intranasal drops,while the control group was given an equal volume of sterile water.The glucose tolerance level and pancreatic islet β cell function of mice were evaluated via oral glucose tolerance test at the 6th week of high-fat feeding and 1 week after the administration of STZ by ip.From the 6th week of high-fat feeding to 2 weeks after the administration of STZ,the random blood glucose and fasting blood glucose of mice were measured by a blood glucose meter.Blood samples were taken from subman-dibular veins of 3 mice in each group at 24,48 and 120 h after S protein infection,and lung tissues were taken after euthanization.The pathological changes of lungs of DM mice before and after S protein infection were observed by HE staining.Except for the DM group,blood samples were collected before S protein infection and at 6,24,48,72 and 120 h after infection.The levels of plasma interleukin 1β(IL-1β),IL-2,IL-6,IL-10,IL-17,interferon gamma-induced protein 10(IP-10),interferon γ(IFN-γ),tumor necrosis factor α(TNF-α),monocyte chemotactic protein-1(MCP-1)and granulocyte-colony stimulating factor(G-CSF)were detected by Luminex.The plasma levels of heparan sulfate(HS)were measured by enzyme-linked immunosorbent assay.The levels of cytokines and HS were correlated with the degree of pathological damage by Spearman correlation analysis.RESULTS STZ and high-fat diet could induce DM-like expression in mice,and the random blood glucose(P<0.01)and fasting blood glucose(P<0.05)after 1 week in the hACE2-DM group were significantly higher than in the WT-DM group,and the degree of islet function damage in hACE2-DM mice was significantly higher than that of WT-DM mice(P<0.05).Compared with the DM group,the DM+S group showed more severe pulmonary pathological changes after S protein infection,accompanied by a large number of inflammatory infiltrations and thickening of lung interstitial.Compared with the control group,the levels of pro-inflammatory cytokines G-CSF,IL-6 and IP-10 in the plasma of the WT-S group were significantly increased at 6 h after S pro-tein infection(P<0.01),and those of pro-inflammatory cytokine IL-17 and anti-inflammatory cytokine IL-10 were significantly increased at 24 h after S protein infection(P<0.05).Compared with the control group,the plasma levels of pro-inflammatory cytokines IL-1β,IL-6,TNF-α,MCP-1,G-CSF and IP-10 in the hACE2-S group were significantly increased at 6 h after S protein infection(P<0.05,P<0.01).IL-17 was significantly increased at 24 h and 6 h after S protein infection in the WT-DM+S group and hACE2-DM+S group,respectively(P<0.01,P<0.05).In the hACE2-DM+S group,IFN-γ and IL-1β were signifi-cantly increased in delay to 48 h(P<0.05,P<0.01),and MCP-1 was significantly increased in delay to 72h(P<0.05).Compared with the control group,the level of HS in the plasma of the WT-S group increased significantly(P<0.05,P<0.01)at 6 h and 24 h after S protein infection,but began to decrease at 48 h.At the same time,compared with the WT-S group,the HS level in the WT-DM+S group was slightly increased at 6 h after infection and decreased at 24 h.Compared with the control group,the HS level in the hACE2-S group was significantly increased at 24 h(P<0.01),as was the case with the WT-S group 24 h,48 h and 120 h after S protein infection.At 6 h,24 h and 48 h after S protein infection,the plasma HS level of the hACE2-DM+S group was significantly increased(P<0.01,P<0.05),and the duration of the increase was longer than in the hACE2-S group.Moreover,the levels of IL-1β,IL-10,MCP-1,IP-10,G-CSF and HS in plasma were positively correlated with the degree of lung dam-age in the DM+S group.CONCLUSION In this study,the mouse model of diabetes combined with SARS-CoV-2 spike protein infection has mimicked part of the pathophysiological features of clinical patients,mainly manifested as blunted immune response and elevated HS levels with longer duration to infection alone.IL-1β,IL-10,MCP-1,IP-10,G-CSF and HS may keep track of the course of disease in patients with diabetes combined with SARS-CoV-2 infection.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Objective To explore the predictive value of heart rate variability(HRV)for long-term prognosis in elderly patients with stable coronary heart disease(CHD)based on dynamic electro-cardiogram(ECG).Methods A retrospective trial was conducted on 402 elderly patients with sta-ble CHD admitted to our hospital from January 2015 to December 2018,and all of them were fol-lowed up for 5 years.According to occurrence of major adverse cardiovascular events(MACE)or not,they were divided into a MACE group(n=102)and a control group(n=300).The main clin-ical characteristics and differences in HRV were compared between the two groups.Multivariate logistic regression analysis and ROC curve analysis were used.Results Advanced age,larger ratio of diabetes,more severe coronary artery stenosis,and higher low-frequency power and ratio of low-frequency power/high-frequency power,but lower left ventricular ejection fraction(LVEF)and high-frequency power were observed in the MACE group than the control group(P＜0.01).There was also statistical difference in use of hypoglycemic drugs between the two groups during the follow-up period(P＜0.01).Multivariate logistic regression analysis showed that diabetes,age ≥80 years,LVEF＜50％,coronary artery stenosis ≥70％and ratio of low-frequency power/high-frequency power＞1.16 were independent influencing factors for MACE in elderly patients with stable CHD within 5 years(P＜0.05,P＜0.01).ROC curve analysis indicated that the AUC value for low-frequency power and ratio of low-frequency power/high-frequency power in predic-ting MACE occurrence within 5 years was 0.801(95％CI:0.749-0.854,P=0.000)and 0.798(95％CI:0.752-0.844,P=0.000),respectively,and the value of high-frequency power in predic-ting the absence of MACE was 0.629(95％CI:0.566-0.692,P=0.000).Conclusion HRV is an independent influencing factor for MACE occurrence within 5 years in elderly patients with stable CHD,and it shows certain predictive value for MACE occurrence within 5 years in these patients.

OBJECTIVE To optimize the preparation process of Soft-shelled turtle blood lyophilized powder （STBLP）， and to provide a reference for improving the availability and quality stability of soft-shelled turtle blood （STB）. METHODS STBLP was prepared with vacuum freeze-drying. Taking the solubility as the index， the preparation process parameters of STBLP were optimized by single factor experiment and Box-Behnken response surface method. RESULTS The optimal freeze-drying process for STBLP was obtained： pre-freezing time of 4 h， total drying time of 13 h （before at 0 ℃）， and resolution drying temperature of 25 ℃. The average solubility of 3 batches of STBLP prepared according to the optimal process was 95.72% （RSD＝0.68%， n＝3）， the relative error of which was －0.97% to the theoretical solubility （96.66%）. CONCLUSIONS Optimized lyophilization process in this study are stable and feasible， the solubility of the prepared sample is high.

Metabolic associated fatty liver disease (MAFLD) is currently one of the most important liver diseases worldwide, and its incidence rate is increasing year by year. This article summarizes the current research status of medical treatment of MAFLD, including lifestyle changes and individualized drug treatment. Lifestyle changes include diet management, exercise intervention, biological clock adjustment, and psychological intervention, and individualized drug treatment includes insulin sensitizer, vitamin E, weight-loss and lipid-lowering drugs, liver-protecting and transaminase-lowering drugs, and traditional Chinese medicine treatment. At the same time, multidisciplinary treatment is the trend of clinical treatment of MAFLD.

OBJECTIVE: To investigate the therapeutic mechanism of resveratrol (RES) for Alzheimer's disease (AD) in light of network pharmacology. METHODS: We searched PubChem, BATMAN-TCM, Genecards, AD, TTD, String 11.0, AlzData, SwissTargetPrediction, Metascape and other databases for the therapeutic targets of RES and human AD-related targets. The intersection was determined using Venny 2.1 to obtain the therapeutic targets of RES for AD. The protein-protein interaction (PPI) network was constructed, the gene ontology (GO) was enriched and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG pathway) were analyzed. Cytoscape 3.7.1 software was used to construct a target-signaling pathway network of RES in the treatment of AD. Molecular docking verification was carried out on SwissDock (http://www.swissdock.ch/docking). We examined a 293Tau cell model of AD for changes in protein levels of pS396, pS199, Tau5, CDK5, glycogen synthase kinase 3β (GSK3β) and p-GSK3β in response to RES treatment using Western blotting. RESULTS: We obtained 182 targets of RES, 525 targets related to AD, and 36 targets of RES for AD treatment, among which 34.6% of the targets were protein-modifying enzymes, 27.7% were metabolite invertase, 13.8% were gene-specific transcriptional regulators, and 10.3% were transporters. The core key targets of RES in the treatment of AD included INS, APP, ESR1, MMP9, IGF1R, CACNA1C, MAPT (microtubule- associated protein Tau), MMP2, TGFB1 and GSK3B. Enrichment analysis of GO biological process suggested that the biological function of RES in AD treatment mainly involved the response to β-amyloid protein, positive regulation of transferase activity, the transmembrane receptor protein tyrosine kinase signaling pathway, regulation of behavior, learning or memory, aging, and transmembrane transport. KEGG pathway enrichment analysis showed that the most significantly enriched signaling pathways were AD pathway, PI3K-AKT signaling pathway, cGMP-PKG signaling pathway, and MAPK signaling pathway. Molecular docking results showed that RES had strong binding with ESR1, GSK3B, MMP9, IGF1R, APP and INS. In the cell model of AD, treatment with 50 μmol/L RES for 12 h significantly reduced the levels of pS396 and pS199 by regulating CDK5 and GSK3β activity ( CONCLUSIONS RES produces therapeutic effects on AD by acting on multiple targets and affecting multiple signaling pathways and improves AD-associated pathologies
Alzheimer Disease/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Resveratrol/pharmacology*

Objective:To evaluate the diagnostic value of digital breast tomosynthesis (DBT) and digital mammography (DM) for radial lesions.Methods:The data of 76 patients (78 lesions) with radial lesions confirmed by operation and pathology on DBT between December 2016 and May 2020 in the Affiliated Hospital of Qingdao University were analyzed retrospectively. Taking pathological results as the gold standard, 78 lesions were divided into benign radial lesions ( n=46) and malignant radial lesions ( n=32), and their DBT features were compared. According to the standard of breast imaging report and data system (BI-RADS), the wheel-spoke structure, central density, overall size, central size and surrounding burr length of the two groups of radial lesions were compared on DBT. Results:The detection rates of DM and DBT for 78 radial lesions were 59.0% (46/78) and 100% (78/78), the difference had statistically significant ( P<0.05). The diagnostic accuracy rates of DM and DBT for 78 radial lesions was 65.2% (30/46) and 74.4% (58/78), the difference had no statistically significant ( P>0.05). The sensitivity, specificity, misdiagnosis rates, missed diagnosis rates of DM and DBT in the diagnosis of malignant radial lesions were 64.3%(18/28) and 84.4%(27/32), 66.7% (12/18) and 67.4%(31/46), 33.3%(6/18) and 32.6%(15/46), 35.7%(10/28) and 15.6%(5/32), respectively. The difference was not statistically significant ( P>0.05). There were significant differences in the overall size of lesions [18.0 (14.9, 29.2) mm, 26.5 (20.2, 34.9) mm], central size [3.5 (2.5, 4.5) mm, 4.5 (3.5, 5.5) mm] and peripheral burr length [(11±6) mm, (13±4) mm] between benign and malignant radial lesions on DBT ( P<0.05). When the central size of the lesion was 5 mm, there was significant difference in the distribution of benign and malignant radial lesions ( P<0.05), and when the overall size of the lesion was 2 cm, there was significant difference in the distribution of benign and malignant radial lesions ( P<0.05). Conclusion:DBT can improve the detection and diagnosis accuracy of radial lesions, and provide an important basis for clinicians to make surgical treatment decisions.

Objective:To explore the value of the quantitative fecal immunochemical test (FIT) for primary colorectal cancer screening in health check-up population.Methods:A total of 468 health check-up participants who underwent quantitative FIT and colonoscopy at the First Affiliated Hospital of Soochow University from January 2018 to December 2019 were enrolled into this study. The participants were divided into two groups-the negative group(FIT<100 μg/L)and the positive group(FIT≥100 μg/L) according to the results of the quantitative FIT. We compared the detection rate of colorectal polyps and colorectal advanced cancer between the two groups, and analyzed the sensitivity and specificity of the quantitative FIT for advanced colorectal cancer and the risk factors of colorectal polyps.Results:The positive rate of quantitative FIT in the healthy population was about 4.6% (95% CI: 4.27%-4.93%). The detection rate of colorectal polyps in the positive group was significantly higher than that of the negative group (51.53%, 95% CI: 45.81%-57.25%) vs (34.28%, 95% CI: 27.25%-41.31%, P<0.001). The sensitivity and specificity of the quantitative FIT for advanced colorectal cancer was 98.55% and 56.77%, respectively. The positive predictive value of the quantitative FIT for advanced colorectal cancer was 50.37%, while the negative predictive value was 98.88%. With the increase of FIT value, the detection rate of advanced cancer was increased (χ2 =20.08, P<0.001). The multivariate logistic regression of colorectal cancer suggested that the risk of colorectal polyps in patients with a history of diabetes was significantly higher ( OR=3.28, 95% CI: 1.45-7.41, P=0.004); the risk of colorectal polyps in men was also significantly higher ( OR=3.05, 95% CI: 1.40-6.65, P=0.005). Conclusions:Quantitative FIT is an ideal non-invasive examination for primary colorectal cancer screening for a health check-up population. Patients with negative FIT are less likely to develop colorectal cancer. Diabetes history, male, and age are independent risk factors for colorectal cancer.