OBJECTIVE: To investigate the effect of danusertib (Danu), an inhibitor of Aurora kinase, on the proliferation, cell cycle, apoptosis, and autophagy of hepatocellular carcinoma HepG2 cells and explore the underlying mechanisms. METHODS: MTT assay was used to examine the effect of Danu on the viability of HepG2 cells to determine the IC50 of Danu. The effect of Danu on cell cycle distribution, apoptosis and autophagy were determined using flow cytometry. Western blotting was used to detect the expressions of the proteins related to cell cycle, apoptosis and autophagy. Chloroquine was used to suppress Danuinduced autophagy to test the apoptosis-inducing effect of Danu. RESULTS: Danu significantly inhibited the proliferation of HepG2 cells with IC of 39.4 μmol and 14.4 μmol at 24 h and 48 h, respectively. Danu caused cell cycle arrest in G/M phase in HepG2 cells and led to polyploidy accumulation via up-regulating the expressions of p53 and p21 and down-regulating the expressions of cyclin B1 and DC2. Danu also caused apoptosis of HepG2 cells through up-regulating the expressions of Bax, Puma, cleaved caspase-3, cleaved caspase-9, cleaved PARP and cytochrome C and down-regulating the expressions of Bcl-xl and Bcl-2. Danu induced autophagy via activating AMPK signaling and inhibiting PI3K/PTEN/AKT/mTOR axis, and inhibition of Danu-induced autophagy with chloroquine enhanced the pro-apoptotic effect of Danu. CONCLUSIONS Danu inhibits cell proliferation and induces cell cycle arrest in G/M phase, apoptosis and cytoprotective autophagy in HepG2 cells.
Apoptosis ; drug effects ; Autophagy ; drug effects ; Benzamides ; pharmacology ; Carcinoma, Hepatocellular ; pathology ; Cell Cycle ; drug effects ; Cell Division ; drug effects ; Cell Proliferation ; drug effects ; Hep G2 Cells ; Humans ; Liver Neoplasms ; pathology ; Neoplasm Proteins ; metabolism ; Protein Kinase Inhibitors ; pharmacology ; Pyrazoles ; pharmacology

Objective: To study the effect of orthodontic treatment on alveolar bone density and epidermal growth factor (EGF) expression in patients with periodontal disease. Methods : 50 patients with periodontal disease admitted into our hospital from January 2015 to January 2016 were selected as research object. Results : Before treatment, patients were given dental health instruction. Under the conditions of patients agreeing and cooperating, patients received orthodontic treatment. The changes of alveolar bone density, EGF in blood, saliva, gingival crevicular fluid (GCF), indexes of periodontal inflammation (gingival index, papilla Bleeding index, probing depth) of patients before and after treatment for one month were compared. Before treatment, the mandibular alveolar bone density was significantly higher than maxillary alveolar bone density (P < 0.05); After treatment, the maxillary and mandibular alveolar bone density were significantly lower than before treatment, and maxillary bone density was significantly lower than mandibular bone density (P < 0.05); After one-month treatment, the concentration of EGF expression in blood, saliva compared with before treatment, there was no statistical significance (P > 0.05); After one-month treatment, the concentration of EGF expression in GCF was significantly higher than before treatment (P < 0.05); Before and after treatment for one month, the concentration of EGF expression in GCF was significantly higher than blood, saliva (P < 0.05); After treatment, the GI, PBI, PD levels were significantly lower than before treatment (P < 0.05); After treatment, flow of saliva and GCF were significantly higher than before treatment (P < 0.05). Conclusion Orthodontic treatment has certain influence on EGF expression in GCF, but has no obvious influence on EGF expression in blood and saliva; The increase of EGF expression derives from periodontal tissue cells and has close association with periodontal remodeling, periodontal tissue cells can promote self-remodeling through autogenous regulation and local humoral regulation.

OBJECTIVE To evaluate the efficacy and safety of different drug regimens in the treatment of children with Kawasaki disease， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from the Cochrane Library， Medline， Embase， CINAHL， Web of Science， ProQuest， Google Scholar， CNKI， Wanfang Data， Baidu academic database， World Health Organization International Clinical Trials Registration Platform and ClinicalTrials. gov， randomized controlled trials （RCTs） about intravenous immunoglobulin （IVIG）+glucocorticoid or cyclosporine or tumor necrosis factor-alpha （TNF-α） blocker （trial group） versus standard IVIG therapy （control group） were collected from the establishment of the database to Feb. 28th， 2023. After screening the literature， extracting data， and evaluating the quality of the literature， Stata 14.2 software was used for network meta-analysis. RESULTS Ten RCTs with a total of 1 323 participants involving six measures were included： standard IVIG therapy， glucocorticoid therapy，cyclosporine therapy， TNF- α blocker therapy， remedial glucocorticoid therapy and remedial TNF- α blocker therapy. Results of network meta-analysis showed that the incidence of coronary artery aneurysms （CAA） at 4-8 weeks was significantly lower in patients receiving glucocorticoid therapy than receiving standard IVIG therapy and TNF-α blocker therapy. The incidences of CAA at 4-8 weeks in children treated with remedial glucocorticoid therapy and remedial TNF- α blocker therapy were significantly higher than those treated with glucocorticoid therapy； there was no significant difference in the incidence of CAA at 4-8 weeks among other interventions （P＞ 0.05）； network meta-order of the incidence was glucocorticoid therapy＜cyclosporine therapy＜standard IVIG therapy＜remedial TNF-α blocker therapy＜remedial glucocorticoid therapy＜TNF-α blocker therapy. The incidence of initial IVIG resistance in children receiving cyclosporine therapy was significantly lower than those receiving standard IVIG therapy； there was no significant difference in the incidence of initial IVIG resistance among other interventions （P＞0.05）； network meta-order of the incidence was cyclosporine therapy＜glucocorticoid therapy＜TNF-α blocker therapy＜standard IVIG therapy. There was no significant difference in the incidence of ADR among different interventions （P＞0.05）； network meta-order of the incidence was remedial TNF-α blocker therapy＜TNF-α blocker therapy＜standard IVIG therapy＜glucocorticoid therapy＜cyclosporine therapy. CONCLUSIONS Glucocorticoid therapy at the initial treatment can significantly reduce the risk of CAA at 4-8 weeks in children with Kawasaki disease； cyclosporine has a significant effect on improving initial IVIG resistance， and the use of TNF-α blocker in the remedial stage may have the lowest incidence of adverse reactions.

BACKGROUND: The basis of individualized treatment should be individualized mortality risk predictive information. The present study aimed to develop an online individual mortality risk predictive tool for acute-on-chronic liver failure (ACLF) patients based on a random survival forest (RSF) algorithm. METHODS: The current study retrospectively enrolled ACLF patients from the Department of Infectious Diseases of The First People's Hospital of Foshan, Shunde Hospital of Southern Medical University, and Jiangmen Central Hospital. Two hundred seventy-six consecutive ACLF patients were included in the present study as a model cohort (n = 276). Then the current study constructed a validation cohort by drawing patients from the model dataset based on the resampling method (n = 276). The RSF algorithm was used to develop an individual prognostic model for ACLF patients. The Brier score was used to evaluate the diagnostic accuracy of prognostic models. The weighted mean rank estimation method was used to compare the differences between the areas under the time-dependent ROC curves (AUROCs) of prognostic models. RESULTS: Multivariate Cox regression identified hepatic encephalopathy (HE), age, serum sodium level, acute kidney injury (AKI), red cell distribution width (RDW), and international normalization index (INR) as independent risk factors for ACLF patients. A simplified RSF model was developed based on these previous risk factors. The AUROCs for predicting 3-, 6-, and 12-month mortality were 0.916, 0.916, and 0.905 for the RSF model and 0.872, 0.866, and 0.848 for the Cox model in the model cohort, respectively. The Brier scores were 0.119, 0.119, and 0.128 for the RSF model and 0.138, 0.146, and 0.156 for the Cox model, respectively. The nonparametric comparison suggested that the RSF model was superior to the Cox model for predicting the prognosis of ACLF patients. CONCLUSIONS The current study developed a novel online individual mortality risk predictive tool that could predict individual mortality risk predictive curves for individual patients. Additionally, the current online individual mortality risk predictive tool could further provide predicted mortality percentages and 95% confidence intervals at user-defined time points.
Acute-On-Chronic Liver Failure ; Humans ; Prognosis ; Proportional Hazards Models ; ROC Curve ; Retrospective Studies

Objective To investigate the possibility and surgical effect of simultaneous tympanoplasty to chronic suppurative otitis media in the period of infection. Methods Forty-eight cases (48 ears) with chronic suppurative otitis media in the period of infection (31 with cholesteatoma, 17 with caries) were underwent simultaneous Wullstein Ⅱ and Ⅲ tympanoplasty on the complete elimination of the lesions (typical or modified mastoidectomy). Results All eases had dry ears within 4-10 weeks with average of 7 weeks. The air-bone gap within 10 dB was in 11 eases, 15 to 20 dB in 25 cases, 25 to 30 dB in 9 eases, no change or worse in 3 eases. Conclusions Infection is not the absolute eontraindication to the tympanoplasty in treating chronic suppurative otitis media, Wullstein Ⅲ tympanoplasty plus mastoid cavity obliteration and eonchaplasty is a suitable choice to treating chronic suppurative otitis media on the complete elimination of lesions and reconstruction of the ventilation system among mastoid cavity, tympanum and eustachian. The malfunction of eustachian is the main eanse to failure of surgery.

Humans ; Stomach Neoplasms/pathology* ; Gastric Mucosa/pathology* ; Adenocarcinoma/pathology*

Objective: The underlying mechanism of Ezrin in ovarian cancer (OVCA) is far from being understood. Therefore, this study aimed to assess the role of Ezrin in OVCA cells (SKOV3 and CaOV3) and investigate the associated molecular mechanisms. Methods: We performed Western blotting, reverse transcription-quantitative polymerase chain reaction, MTT, cell colony, cell wound healing, transwell migration and invasion, RhoA and Rac active pull down assays, and confocal immunofluorescence experiments to evaluate the functions and molecular mechanisms of Ezrin overexpression or knockdown in the proliferation and metastasis of OVCA cells. Results: The ectopic expression of Ezrin significantly increased cell proliferation, invasiveness, and epithelial-mesenchymal transition (EMT) in OVCA cells. By contrast, the knockdown of endogenous Ezrin prevented OVCA cell proliferation, invasiveness, and EMT. Lastly, we observed that Ezrin can positively regulate the active forms of RhoA rather than Rac-1 in OVCA cells, thereby promoting robust stress fiber formation. Conclusion Our results indicated that Ezrin regulates OVCA cell proliferation and invasiveness by modulating EMT and induces actin stress fiber formation by regulating Rho-GTPase activity, which provides novel insights into the treatment of the OVCA.
Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cytoskeletal Proteins/metabolism* ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Invasiveness ; Ovarian Neoplasms/pathology* ; Stress Fibers/metabolism* ; rhoA GTP-Binding Protein/metabolism*

Objective : To investigate the neurobehavioral development of young children aged 24 to 60 months in Shunde and explore the factors influencing the development of young children and provide reference for the interven- tion of neurobehavioral development delays in young children． Methods : A retrospective cohort study was used to enroll the young children who were initially screened by the Pediatric Neuropsychological Developmental Scale (Pe- diatric Heart Scale) with a score of ≤85 was included in the study．With a score of ≤85，the young children might be at risk of developmental delays，and needed to be further diagnosed by the GESELL Developmental Diagnostic Scale，the basic information of the young children and their mothers at the time of birth were investigated，as well as basic information about the young children at the time of completing the GESELL Developmental Diagnostic Scale was collected. Results : A total of 271 young children were included，196 males and 75 females．Young children had the lowest developmental quotient (DQ) in the language domain among the five domains (P＜0. 001) ．Multiple lin- ear regression models showed : compared with girls，the language domain DQ of boys decreased by 5. 321 points (P = 0. 049，95% CI : －10. 620 －－0. 021) ，and the personal-social domain DQ decreased by 4. 474 points (P = 0. 023，95% CI : －8. 316 －－0. 631) ．Compared with young children via natural vaginal delivery (NVD) ，the gross motor domain DQ of young children via caesarean section ( CS) decreased by 4. 890 points (P = 0. 008，95% CI : - 8. 499 －－1. 281 ) ，the fine motor domain DQ decreased by 3. 373 points ( P = 0. 037，95% CI : －6. 532 - - 0. 213) ，the language domain DQ decreased by 7. 621 points (P = 0. 004，95% CI : －12. 826 －－2. 416) ，per- sonal-social domain DQ decreased by 6. 232 points (P = 0. 001，95% CI : －10. 006 －－2. 457) ．The results of bi- nary logistic regression models showed，compared with young children via NVD，the risk of gross motor domain retar- dation in young children increased ( OR = 1. 763，95% CI : 1. 003－3. 100) ，the risk of fine motor domain retardation increased ( OR = 2. 217，95% CI : 1. 235－3. 980) ，the risk of language domain retardation increased ( OR = 3. 306， 95% CI : 1. 080 －10. 124) . Conclusion Young children with suspected neurobehavioral delays were more likely to have delayed development in language domain than in other domains，boys had lower DQ in language domain and personal-social domain than girls，and the development of young children via CS was slower than that via NVD．Fo- cus should be on the language development of young children especially on the language and personal-social devel- opment of boys．Carefully chose delivery way．Focus should be placed on assessment of young children's comprehen- sive neurobehavioral development in early time.

OBJECTIVETo investigate the inhibitory effect of 420 nm intense pulsed light on Trichophyton rubrum growth in vitro and explore the mechanism.

METHODSThe fungal conidia were divided into treatment group with intense pulse light irradiation and control group without irradiation. The surface areas of the fungal colonies were photographed before irradiation and on the 2nd and 3rd days after irradiation to observe the changes in fungal growth. The viability of the fungus in suspension was detected at 6 h after irradiation using MTT assay. The intracellular reactive oxygen species (ROS) level in the fungus was determined using DCFH-DA fluorescent probe, and the MDA content was detected using TBA method.

RESULTSIntense pulse light (420 nm) irradiation caused obvious injuries in Trichophyton rubrum with the optimal effective light dose of 12 J/cmin 12 pulses. At 6 h after the irradiation, the fungus in suspension showed a 30% reduction of viability (P<0.05), and the fungal colonies showed obvious growth arrest without further expansion. Compared to the control group, the irradiated fungus showed significant increases in ROS level and MDA content (P<0.05).

CONCLUSIONIntense pulse light (420 nm) irradiation can induce oxidative stress in Trichophyton rubrum to lead to fungal injuries and death.

OBJECTIVETo study the expression of transforming growth factor-β1 (TGF-β1) and plasminogen activator inhibitor-1 (PAI-1) and its significance in premature infants with bronchopulmonary dysplasia (BPD).

METHODSA retrospective analysis was performed on the clinical data of 96 very low birth weight infants (gestational age of ≤ 32 weeks) who survived for more than 28 days and were admitted to the Neonatal Intensive Care Unit between January 2010 and December 2012. These subjects were divided into BPD group (n=21) and non-BPD group (n=75). The expression of TGF-β1 and PAI-1 in blood was measured by ELISA.

RESULTSThe levels of TGF-β1 and PAI-1 in the BPD group increased gradually from the 7th day to the 14th day and then to the 21st day after birth, and were significantly higher than in the non-BPD group at all time points (P<0.01). The TGF-β1 and PAI-1 levels in the non-BPD group on the 7th, 14th, and 21st days after birth were not significantly different from each other (P>0.05).

CONCLUSIONSThe expression of TGF-β1 and PAI-1 in blood is elevated in premature infants with BPD, which may be associated with the development of BPD.

Bronchopulmonary Dysplasia ; etiology ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; Male ; Plasminogen Activator Inhibitor 1 ; blood ; Retrospective Studies ; Transforming Growth Factor beta1 ; blood