Predicting Survival Using Whole-Liver MRI Radiomics in Patients with Hepatocellular Carcinoma After TACE Refractoriness.

PURPOSE: To develop a model based on whole-liver radiomics features of pre-treatment enhanced MRI for predicting the prognosis of hepatocellular carcinoma (HCC) patients undergoing continued transarterial chemoembolization (TACE) after TACE-resistance. MATERIALS AND METHODS: Data from 111 TACE-resistant HCC patients between January 2014 and March 2018 were retrospectively collected. At a ratio of 7:3, patients were randomly assigned to developing and validation cohorts. The whole-liver were manually segmented, and the radiomics signature was extracted. The tumor and liver radiomics score (TLrad-score) was calculated. Models were trained by machine learning algorithms and their predictive efficacies were compared. RESULTS: Tumor stage, tumor burden, body mass index, alpha-fetoprotein, and vascular invasion were revealed as independent risk factors for survival. The model trained by Random Forest algorithms based on tumor burden, whole-liver radiomics signature, and clinical features had the highest predictive efficacy, with c-index values of 0.85 and 0.80 and areas under the ROC curve of 0.96 and 0.83 in the developing cohort and validation cohort, respectively. In the high-rad-score group (TLrad-score > - 0.34), the median overall survival (mOS) was significantly shorter than in the low-rad-score group (17 m vs. 37 m, p < 0.001). A shorter mOS was observed in patients with high tumor burden compared to those with low tumor burden (14 m vs. 29 m, p = 0.007). CONCLUSION: The combined radiomics model from whole-liver signatures may effectively predict survival for HCC patients continuing TACE after TACE refractoriness. The TLrad-score and tumor burden are potential prognostic markers for TACE therapy following TACE-resistance.

Influencing factors of hospitalization cost of hypertension patients in traditional Chinese medicine hospitals.

Objectives: This study aimed to analyze the influencing factors of hospitalization cost of hypertensive patients in TCM (traditional Chinese medicine, TCM) hospitals, which can provide a scientific basis for hospitals to control the hospitalization cost of hypertension. Methods: In this study, 3,595 hospitalized patients with a primary diagnosis of tertiary hypertension in Tianshui City Hospital of TCM, Gansu Province, China, from January 2017 to June 2022, were used as research subjects. Using univariate analysis to identify the relevant variables of hospitalization cost, followed by incorporating the statistically significant variables of univariate analysis as independent variables in multiple linear regression analysis, and establishing the path model based on the results of the multiple linear regression finally, to explore the factors influencing hospitalization cost comprehensively. Results: The results showed that hospitalization cost of hypertension patients were mainly influenced by length of stay, age, admission pathways, payment methods of medical insurance, and visit times, with length of stay being the most critical factor. Conclusion: The Chinese government should actively exert the characteristics and advantages of TCM in the treatment of chronic diseases such as hypertension, consistently optimize the treatment plans of TCM, effectively reduce the length of stay and steadily improve the health literacy level of patients, to alleviate the illnesses pain and reduce the economic burden of patients.

A Novel Rat Model to Simulate the Benign Esophageal Stricture Induced by Endoscopic Submucosal Dissection.

Objective: This study aimed to establish a rat model that simulates benign esophageal strictures induced by endoscopic submucosal dissection (ESD). Materials and Methods: Sixteen male Sprague-Dawley rats were randomly divided into mucosal resection (n = 8) and sham-operated groups (n = 8). The rats in the mucosal resection group underwent a 5-mm three-fourths mucosal resection by way of a 3-mm incision in the distal esophagus under direct visualization via laparotomy. Rats in the sham-operated group underwent a 3-mm incision of the muscularis propria layer in the distal esophagus via laparotomy without mucosal resection. Dysphagia score, weight gain, mucosal constriction rate, and histology were evaluated 2 weeks after surgery. Results: Technical success was achieved in all the animals. One rat in the mucosal resection group died of infection, and no other complications were observed. Weight gain (P < 0.001) and luminal diameter derived from the esophagograms (P < 0.001) were significantly lower in the mucosal resection group than those in the sham-operated group. Dysphagia score (P < 0.001) and mucosal constriction rate (P < 0.001) were significantly higher in the mucosal resection group than those in the sham-operated group. The inflammation grade (P = 0.002), damage to the muscularis propria (P < 0.001), number of nascent microvessels (P = 0.006), and degree of α-SMA positive deposition (P = 0.006) were significantly higher in the mucosal resection group. Conclusion: A rat model of benign esophageal stricture induced by ESD was successfully and safely established by mucosal resection.

Effects of 3.0T magnetic resonance noise on the hearing of children aged 0-12 years with routine hearing protection / 西安交通大学学报(医学版)

Objective To explore the effect of exposure to noise of 3.0T magnetic resonance imaging(MRI)on children's cochlear function.Methods We prospectively recruited 72 children who underwent cranial MRI examination at our hospital from May to November 2018;3M earplugs and sponge mats were used for hearing protection during MRI scanning.Noise level(dBA)of each MRI sequence was detected with a nonmagnetic microphone and a sound level meter.Distortion product otoacoustic emissions(DPOAE)test at 2-7 kHz was performed 24 hours before and 30 minutes after the MRI examination.Paired t-test or Wilcoxon signed-rank test was used to analyze differences in DPOAE amplitude before and after the MRI examination.Results The average noise level of MRI measured in the study was(107.7±3.92)dBA.Compared with that before the MRI examination,the DPOAE amplitude(dB)changed little after the MRI examination;the range of amplitude differences in each age group was as follows:left ear(-0.24-1.10)and right ear(-0.24-0.74)in the 0-1 year-old group;left ear(-0.07-0.59)and right ear(-0.57-0.75)in the 2-5 year-old group;left ear(-0.36-0.44)and right ear(-0.30-0.57)in the 6-12 year-old group.No statistically significant difference was found(correction P＞0.05).Conclusion No potential impact of 3.0T MRI noise on children's cochlear function was observed under routine hearing protection.

Finite element analysis of thumb thrust in lumbar fixed-point rotation manipulation / 中国组织工程研究

BACKGROUND:Lumbar fixed-point rotation operation needs collaborative operation of the doctor's hands,and outputs rotation and thumb thrust.Lumbar disc herniation can be treated through disc displacement and adjusting stress distribution.However,the mechanical effects of thumb thrust and the biomechanical effects of loading direction on manipulative effects remain unclear. OBJECTIVE:To compare the biomechanical difference of lumbar fixed-point rotation manipulation for treating lumbar disc herniation under different thrust directions. METHODS:The L3-5 normal three-dimensional finite element model was constructed and validity was verified.According to the intervertebral disc degeneration Pfirrmann grade,intervertebral disc degeneration was simulated by modifying the L4/5 intervertebral space height,the volume of the nucleus pulposus,as well as the material parameters of the annulus fibrosus,nucleus pulposus,and ligament.Finally,the pathological model of L4/5 moderate disc degeneration with left para-central herniation was constructed,and then the pathological models were used as research objects.Simulation technique:spinning to the right;taking the condition on changing the direction of the thumb thrust to establish three modes of operation(M1:thumb push to the left;M2:thumb push to the right;M3:no thrust push).The protrusion displacement and the disc stress,and the stress and strain of the facet joint cartilage were compared in the three operating modes. RESULTS AND CONCLUSION:(1)Maximum displacement value of L4/5 disc herniation:displacement was 2.672 3 mm for M1,1.156 1 mm for M2,1.826 4 mm for M3,M1＞M3＞M2.(2)The maximum Von Mises stress of L4/5 discs was 1.846 7 MPa for M1,0.419 0 MPa for M2,and 1.257 9 MPa for M3,M1＞M3＞M2.(3)L4/5 bilateral small cartilage produced different degrees of contact stress changes:It was 0.485 5 MPa for M1,0.026 7 MPa for M2,and 0.441 4 MPa for M3,M1＞M3＞M2.Right cartilage contact force was 0.000 5 MPa for M1,0.025 9 MPa for M2,and 0.001 3 MPa for M3,M2＞M3＞M1;the left greater than the right,M1 had the highest value;cartilage strain was consistent with contact stress changes.(4)Different operation modes will have some biomechanical influences on the diseased intervertebral disc and accessory structure.The M1 operation mode can maximize the displacement of protrusion,disc stress and left joint cartilage contact,which can better promote disc displacement,balance stress distribution and reduce facet joint disorder,so the operation is better.

Surgical interventions for symptomatic knee osteoarthritis: a network meta-analysis of randomized control trials.

BACKGROUND: Multiple surgical interventions exist for the treatment of symptomatic knee osteoarthritis, but the surgeon and patient may often have difficulty deciding which interventions are the best option. METHODS: We conducted a systematic review to identify randomized clinical trials (RCTs) that compared complications, revisions, reoperations, and functional outcomes among TKA (total knee arthroplasty), UKA (unicompartmental knee arthroplasty), HTO (high tibial osteotomy), BCA (bicompartmental knee arthroplasty), BIU (bi-unicompartmental knee arthroplasty), and KJD (knee joint distraction). The PubMed, Embase, and Cochrane databases were reviewed for all studies comparing two or more surgical interventions. Direct-comparison meta-analysis and network meta-analysis (NMA) were performed to combine direct and indirect evidence. The risk of bias was assessed using the revised Cochrane risk of bias tool for RCTs. RESULTS: This NMA and systematic review included 21 studies (17 RCTs), with a total of 1749 patients. The overall risk-of-bias assessment of the RCTs revealed that 7 studies had low risk, 5 had some concerns, and 9 had high risk. SUCRA (the surface under the cumulative ranking curve) rankings revealed that KJD had the greatest risk of appearing postoperative complications, revisions, and reoperations, and UKA or TKA had the lowest risk. The majority of comparisons among various treatments showed no difference for functional outcomes. CONCLUSION: Each surgical intervention is noninferior to other treatments in functional outcomes, but UKA and TKA are better options to treat OA according to SUCRA rankings by comparing complications, revisions, and reoperations. KJD is an imperfect option for treating OA. Other treatments should be carefully considered for each patient in accordance with their actual conditions. However, this conclusion is limited by the selection of reviewed publications and individual variation of surgical indications for patients. TRIAL REGISTRATION: This study was registered with Research Registry (reviewregistry1395).

WGCNA-based identification of novel T-cell exhaustion-related gene signatures to predict the prognosis and response to immunotherapy of osteosarcoma patients / 肿瘤

Objective:To screen T-cell exhaustion-related signature genes as the prognostic marker for osteosarcoma and establish a prognostic model for osteosarcoma patients based on weighted gene co-expression network analysis(WGCNA)and Least absolute shrinkage and selection operator(LASSO)-COX regression analysis. Methods:GSE21257 dataset was downloaded from Gene Expression Omnibus(GEO)database for the establishment of the prognostic model for osteosarcoma.4 T-cell exhaustion-related gene sets were downloaded from The Molecular Signatures Database(MisgDB)and their enrichment scores in GSE21257 samples were calculated by single sample gene set enrichment analysis(ssGSEA).WGCNA was carried out to screen the gene module that is highly associated with T-cell exhaustion based on ssGSEA results followed by GO(Gene Ontology)and KEGG(Kyoto Encyclopedia of Genes and Genomes)analysis of the biological processes and signaling transduction pathways that those genes are involved in.The signature genes that are highly associated with the prognosis of osteosarcoma patients were obtained through LASSO-COX regression and a prognostic model was established based on these signature genes.Osteosarcoma-related expression profile data from the GSE21257 and TAEGET datasets on XENA were downloaded from the Gene Expression Omnibus.Clinical information for the training and validation sets was obtained.T-cell exhaustion-related genes were screened using a weighted correlation network analysis.Realtime fluorescence quantitative PCR,COX regression analysis,external dataset and nomogram were used to evaluate the reliability and accuracy of the prognostic model.A immunotherapy-related dataset was used to assess the efficacy of this prognostic model for the prediction of patients'responses to immunotherapy. Results:Analysis results based on the ssGSEA scores showed that T-cell exhaustion-related genes were related to the metastasis and age of osteosarcoma patients.Many T-cell exhaustion-related genes were found to be differentially expressed in metastatic and non-metastatic osteosarcoma patients.1 256 T-cell exhaustion-related genes were identified through WGCNA and these candidate markers were mainly distributed in structures like secretory granule membranes and endocytic vesicles and were involved in T-cell activation.COX regression analysis screened 68 significant prognostic markers out of the 1 256 genes,and 12 signature genes were further confirmed with LASSO-COX regression analysis.A prognostic model was established based on the 12 signature genes.Results of real-time fluorescence quantitative PCR showed a similar trend in the expression of most of the signature genes in different osteosarcoma cell lines.COX regression analysis of the internal and external datasets verified that the risk score calculated with the prognostic model was an independent prognostic factor for osteosarcoma patients,and high-risk score was associated with poor prognosis of the patients.Receiver operating characteristic(ROC)curves demonstrated excellent prognostic efficacy of the model.Nomogram analysis verified the prognostic model is highly accurate and reliable in predicting the prognosis of osteosarcoma patients.Analysis using the immunotherapy-related dataset indicated that this prognostic model could also be used to predict patients'responses to immunotherapy. Conclusion:The 12 signature gene(CD300LB,TRO,SNX3,VENTX,PPM1M,DOT1L,CDC37,NAT9,TRMT1,PPP1R3C,CHTF18 and NSUN5)-based prognostic model can effectively predict the prognosis and responses to immune check-point inhibitors for osteosarcoma patients,which may provide evidence for the prediction of prognosis as well as the selection of immunotherapy plans in clinical practice.

Effects of RNA demethylase FTO inhibitor on function ofglioblastoma stem cells / 中国药理学通报

Aim To investigate the effect of m6A demethylase FTO inhibitor(FB23-2)on human glioblastoma stem cell activity. Methods The effects of FB23-2 and Temozolomide on GSC were detected by CCK-8 assay and neurosphere formation assay. The effect of FB23-2 on self-renewal of GSC was detected by limited dilution assay in vitro. The effect of FB23-2 on the proliferation of GSC was detected by EdU method. The effect of FB23-2 on apoptosis of glioblastoma stem cells was detected by flow cytometry. Results CCK-8 assay showed that FB23-2 could effectively inhibit the cell viability of GSC with IC50 values of 7.11 μmol·L-1 and 4.63 μmol·L-1,respectively. The size and number of GSC neural sphere in FB23-2 treatment group were significantly reduced compared with control group. In vitro limited dilution experiment showed that FB23-2 effectively inhibited the self-renewal ability of GSC. EdU incorporation experiment showed that compared with the control group,the treatment group decreased to(70.59±13.74)% and(50.33±4.53)%,respectively. The apoptotic rates of the treated group were(12.16±1.90)% and(16.77±1.17)% by flow cytometry. Conclusions FTO inhibitor FB23-2 can effectively inhibit GSC growth,self-renewal and the formation of neural sphere. In addition,FB23-2 can inhibit the proliferation of GSC and induce its apoptosis.

External validation of a machine learning model to predict hemodynamic instability in intensive care unit.

BACKGROUND: Early prediction model of hemodynamic instability has the potential to improve the critical care, whereas limited external validation on the generalizability. We aimed to independently validate the Hemodynamic Stability Index (HSI), a multi-parameter machine learning model, in predicting hemodynamic instability in Asian patients. METHOD: Hemodynamic instability was marked by using inotropic, vasopressor, significant fluid therapy, and/or blood transfusions. This retrospective study included among 15,967 ICU patients who aged 20 years or older (not included 20 years) and stayed in ICU for more than 6 h admitted to Taipei Veteran General Hospital (TPEVGH) between January 1, 2010, and March 31, 2020, of whom hemodynamic instability occurred in 3053 patients (prevalence = 19%). These patients in unstable group received at least one intervention during their ICU stays, and the HSI score of both stable and unstable group was calculated in every hour before intervention. The model performance was assessed using the area under the receiver operating characteristic curve (AUROC) and was compared to single indicators like systolic blood pressure (SBP) and shock index. The hemodynamic instability alarm was set by selecting optimal threshold with high sensitivity, acceptable specificity, and lead time before intervention was calculated to indicate when patients were firstly identified as high risk of hemodynamic instability. RESULTS: The AUROC of HSI was 0.76 (95% CI, 0.75-0.77), which performed significantly better than shock Index (0.7; 95% CI, 0.69-0.71) and SBP (0.69; 95% CI, 0.68-0.70). By selecting 0.7 as a threshold, HSI predicted 72% of all 3053 patients who received hemodynamic interventions with 67% in specificity. Time-varying results also showed that HSI score significantly outperformed single indicators even up to 24 h before intervention. And 95% unstable patients can be identified more than 5 h in advance. CONCLUSIONS: The HSI has acceptable discrimination but underestimates the risk of stable patients in predicting the onset of hemodynamic instability in an external cohort.

[Comparison of Clinical Efficacy of Thermal Ablation vs. Surgical Resection of Metachronous Colorectal Liver Metastasis].

Objective: To compare the treatment efficacy of thermal ablation versus surgical resection of metachronous colorectal liver metastasis (CRLM) and to explore the potential candidates suited for thermal ablation. Methods: The data of 319 patients with CRLM who underwent radical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences between November 2007 and January 2021 were retrospectively collected. The patients were divided into two groups, the thermal ablation group and the surgical resection group, according to the actual treatments they received. Propensity score matching (PSM) was applied to balance the baseline characteristics between the two groups. Cox regression analysis was conducted to identify the risk factors for recurrence and survival. Survival analysis was performed for intergroup comparison. Results: Using PSM at 1∶1 ratio, 92 patients were included in the thermal ablation group and 92 patients were included in the surgical resection group.The median overall survival (OS) in the thermal ablation group was 49 (95% confidence interval, 37-76) months, which was shorter than that of the surgical resection group ( P<0.01). Multivariate Cox regression analysis indicated that the T staging of primary tumor, number of metastatic tumor, maximum diameter of metastatic tumor, preoperative serum carcinoembryonic antigen (CEA) level, and treatment method were independent risk factors affecting OS. Compared with the surgical resection group, the thermal ablation group demonstrated higher hepatic recurrence rate (59.8% vs. 23.9%, P<0.01), shorter disease-free survival (DFS) (10 months vs. 33 months, P<0.01), and shorter length of hospital stay (7 days vs. 14 days, P<0.01). Subgroup analysis, conducted with the data of the 319 patients before PSM, showed that early recurrence patients who underwent thermal ablation or surgical resection had comparable median OS (29 months vs. 42 months, P=0.35). For the non-early recurrence patients, the median OS of the thermal ablation group was shorter than that of the surgical resection group ( P<0.01). Conclusion: For the treatment of CRLM, the efficacy of surgical resection was better than that of thermal ablation. However, the efficacy was comparable between the two treatments for early recurrence patients of CRLM.

Surface roughness, gloss and sequential polishing times of various chairside computer aided design/manufacturing restorative materials / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effect of polishing on surface roughness, gloss and optimum polishing time of various computer aided design/computer aided manufacturing (CAD/CAM) restorative materials and to provide a proper polishing procedure for dental clinicians.@*METHODS@#Five CAD/CAM restorative materials including vita mark Ⅱ (VM), vita enamic (VE), lava ultimate (LU), shofu block HC (SB) and brilliant crios (BC) were selected. Six specimens were prepared for each material. The specimen was fixed on a custom-made polishing apparatus and sequentially polished with Sof-Lex poli-shing disk system including medium disk (with abrasive particle sizes of 10-40 μm), fine disk (with abrasive particle sizes of 3-9 μm) and superfine disk (with abrasive particle sizes of 1-7 μm). Surface roughness (Ra value) and gloss value were measured every 10 seconds until the numerical values were no longer changed. Then the surface roughness, gloss value and polishing time were recorded and the specimen was moved to the next sequence of polishing. Finally, statistical analysis was performed using SPSS 24.0.@*RESULTS@#For all the restorative materials, the Ra values were significantly reduced (P < 0.05) and the gloss values were significantly increased (P < 0.05) after sequentially polishing with Sof-Lex disks. No significant difference was detected among Ra values of all the tested materials (P>0.05) after sequential polishing. The gloss values of LU [(68.1±4.5) GU] and BC [(68.2±5.8) GU] were significantly higher than those of VE [(48.1±8.1) GU] and BC [(53.2±5.8) GU], P < 0.05. To obtain optimal surface smoothness, VM cost the shortest polishing time [40 (30, 55) s] among all the restorative materials (P < 0.05). No significant differences in the total polishing time were observed among VE [140 (135, 145) s], LU [130 (120, 140) s], SB [140 (130, 150) s] and BC [130 (120, 140) s], P>0.05.@*CONCLUSION@#The surface roughness of all CAD/CAM restorative materials were decreased after sequentially polishing with Sof-Lex disk system. To obtain the smoothest surface, different types of restorative materials might need different polishing times using Sof-Lex polishing disk system. For ceramic restorative material VM, we recommend polishing only with medium disk for 40 s. For hybrid restorative material VE and composite restorative material LU, SB and BC, we recommend polishing with medium disk, fine disk and superfine disk in sequence for 130-140 s in total.

[Clinical and Neuroimaging Analysis of 24 Cases of Sturge-Weber Syndrome].

OBJECTIVE: To analyze the clinical manifestations and neuroimaging characteristics of Sturge-Weber syndrome (SWS), to describe the manifestations of facial port-wine stains (PWS) of SWS, and to explore the screening opinions for SWS. METHODS: A retrospective analysis was performed on the general condition, clinical manifestations, and neuroimaging results of 24 SWS patients from the dermatology department of West China Hospital of Sichuan University between 2017 and 2019. Three different facial PWS distribution methods (traditional anatomical distribution, facial trigeminal nerve distribution, and facial embryological vasculature distribution) in SWS patients were Analysed. RESULTS: Among the 24 patients, 50% were male and 50% were female, with an average age of (18.9±14.0) years (range 1 to 54 years old). 12 cases were SWS type Ⅰ, and the other 12 cases were type Ⅱ. All patients had facial PWS at birth, and the facial PWS of 13 cases (54.2%) were thickened. According to the anatomical division, all the PWS involved the upper and middle face (above the oral commissure); according to the trigeminal nerve distribution, 100% (24/24) patients involve the V2 area; according to the distribution of facial embryological vasculature, 95.8% (23/24) of the patients involved frontal region. 22 patients had ophthalmic abnormalities, the most common was glaucoma (70.8%), and 4 patients had a history of epilepsy. The typical neuroimaging presentations of SWS include leptomeningeal enhancement, cortical calcification, enlarged choroid plexus, focal cerebral atrophy, abnormal intracranial vessels, and local thickening of the skull. CONCLUSION: Early intervention is recommended for facial PWS in patients with SWS , and ophthalmological screening should be performed on children with PWS found in any part of the upper and middle face after birth. Moreover, neuroimaging examination (MRI) for patients with high suspicion of SWS should be performed after 1 year old, and regular ophthalmological examination and intraocular pressure measurement is necessary.

Evaluation of wear property of Giomer and universal composite in vivo / 北京大学学报(医学版)

OBJECTIVE@#To observe the wear performance of Giomer and universal composite for posterior restorations by 3D laser scan method, in order to guide the material selection in clinic.@*METHODS@#In this study, 48 patients (108 teeth) were selected according to the inclusion and exclusion criteria. All the patients in need of a minimum of 2 Class Ⅰ and/or Class Ⅱ restorations were invited to join the study. The teeth were restored with Giomer (Beautifil Ⅱ, BF) and universal composite (Filtek Z350, Z350) randomly. The restorations were evaluated at baseline and after 6-, 18-, 48-month using the modified United States Public Health Service (USPHS) criteria for clinical performance. The in vivo images and gypsum replicas were taken at each recall. A 3D-laser scanner and Geomagic Studio 12 were used to analyze the wear depth quantitatively. Statistical analysis was performed with SPSS 20.0.@*RESULTS@#After 4 years, 89.6% patients were recalled. The survival rate of both materials was 95.8% (Kaplan-Meier survival analysis). Seven restorations of the two materials failed due to loss of restoration, bulk fracture, secondary caries and pulp necrosis. The wear patterns of restorations were divided into 2 classes. Pattern Ⅰ: occlusal contact areas showed the deepest and fastest wear depth; pattern Ⅱ: the wear depth was slow and uniform. Both materials showed a rapid wear in the first 6 months. Then the wear rate was decreased. The occlusal wear depth after 4 years were (58±22) μm and (54±16) μm for BF group and Z350 group respectively, which were in accordance with the American Dental Association (ADA) guidelines (wear depth for 3 years < 100 μm). No significant differences (P>0.05) were observed between the two groups. Regarding the restorations with wear pattern Ⅰ, the wear depth of BF group was higher than Z350 group at 6- and 48-month (P < 0.05), while there was no significant difference between restorations with wear pattern Ⅱ (P>0.05).@*CONCLUSION@#Within the limitation of the study, after 4 years, the survival rate and wear resistance of Giomer met ADA guidelines for tooth-colored restorative materials for posterior teeth. When the two materials were applied in occlusal contact areas, wear resistance of Giomer was slightly lower than universal composite resin. No significant difference was found when they were applied in none of the occlusal contact areas.

From pathogenesis of acne vulgaris to anti-acne agents.

Acne vulgaris is a cutaneous chronic inflammatory disorder with complex pathogenesis. Four factors play vital roles in acne pathophysiology: hyperseborrhea and dysseborrhea, altered keratinization of the pilosebaceous duct, Cutibacterium acnes (C. acnes) and inflammation. The main hormones responsible for the development of acne vulgaris include androgens, insulin and insulin-like growth factor-1. Other factors involved in this process are corticotropin-releasing hormone, α-melanocyte-stimulating hormone and substance P. Wnt/ß-catenin signaling pathway, phosphoinositide 3-kinase (PI3K)/Akt pathway, mitogen-activated protein kinase pathway, adenosine 5'-monophosphate-activated protein kinase pathway and nuclear factor kappa B pathway participate in the modulation of sebocyte, keratinocyte and inflammatory cell (e.g. lymphocytes, monocytes, macrophages, neutrophils) activity. Among all the triggers and pathways mentioned above, IGF-1-induced PI3K/Akt/Forkhead box protein O1/mammalian target of rapamycin (mTOR) C1 pathway is the most important signaling responsible for acne pathogenesis. Commonly used anti-acne agents include retinoids, benzoyl peroxide, antibiotics and hormonal agents (e.g. spironolactone, combination oral contraceptive and flutamide). New approaches including peroxisome proliferator-activated receptor γ modifier, melanocortin receptor antagonists, epigallocatechin-3-gallate, metformin, olumacostat glasaretil, stearoyl-CoA desaturase inhibitor omiganan pentahydrochloride, KDPT, afamelanotide, apremilast and biologics have been developed as promising treatments for acne vulgaris. Although these anti-acne agents have various pharmacological effects against the diverse pathogenesis of acne, all of them have a synergistic mode of action, the attenuation of Akt/mTORC1 signaling and enhancement of p53 signal transduction. In addition to drug therapy, diet with no hyperglycemic carbohydrates, no milk and dairy products is also beneficial for treatment of acne.

Effect of intrapulpal pressure on the bonding strength of resin cement to dentin / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the effect of intrapulpal pressure simulation on the micro-tensile bond strength (μTBS) of resin cement to dentin.@*METHODS@#Thirty extracted human third molars were selected. Occlusal enamel was removed to expose dentine surface and teeth with residual dentin thickness of 0.5-2.5 mm were selected. Dye permeation through dentin tubules with or without intrapulpal pressure (IPP) simulation, or after Single Bond Universal (SBU) application on dentin surface with IPP simulation were observed at the end of 0 min, 5 min, 30 min and 2 h. The teeth with residual dentin thickness of (1.0±0.1) mm were divided into 2 groups with IPP simulation of 15 or 0 cmH2O (1 cmH2O=0.098 kPa), which was maintained for 30 min before bonding procedure. SBU was applied on the dentin surface and light cured, then RelyX Ultimate (RLX) cement was heaped on the dentin surface (diameter=10 mm, height=4 mm) and light-cured. After the dentin-resin cement samples were stored in distilled water for 24 h at 37 °C, the samples were cut into beams with cross sectional area of 0.9 mm×0.9 mm for μTSB testing (n=100). The data were analyzed with two independent samples t-test (α=0.05). The fracture mode was observed using scanning electron microscopy (SEM). The results were analyzed with Fisher exact test (α=0.05). The rest of dentin-resin cement samples (five samples for each group) were cut perpendicular to the bonding interface and the morphology of the bonding interface was observed using SEM.@*RESULTS@#The dye permeation through dentin tubules with IPP simulation was faster than those without IPP simulation. The μTSB of RLX to dentin with and without IPP simulation were (26.26±9.78) MPa and (28.70±9.0) MPa, respectively. The most frequent fracture mode was mixed-fracture mode. There was no significant difference between the two groups for neither bond strength nor fracture types distribution (P>0.05). Regarding the morphology of dentin-resin cement bonding interface, both groups showed 4-8 μm finger-like resin tags.@*CONCLUSION@#With SBU pretreatment, the IPP simulation had no influence on the immediate bond strength of RLX to dentin.

Influence of setting time on bond strength of different bioactive pulp capping materials with dental adhesive / 北京大学学报(医学版)

OBJECTIVE@#To investigate influence of setting time on bond strength of different bioactive pulp capping materials with self-etch or etch-and-rinse adhesive.@*METHODS@#Sixty specimens were prepared for each of the three tested capping materials, namely mineral trioxide aggregate (MTA), iRoot BP Plus (BP) and iRoot FS (FS). Specimens of each material were divided into three groups and bonded at three setting time points of the materials respectively: initial setting time (4 h for MTA, 2 h for BP and 20 min for FS), 24 h after application and 7 d after application. The specimen surfaces of each group were treated with self-etch mode or etch-and-rinse mode of one universal adhesive (Single Bond Universal, SBU) (n=10). The bonding area was restricted to a round area with 3 mm diameter, on which composite cylinders were build up with flowable composite and light cured completely. The shear bond strength was tested immediately with a shear strength tester and fracture mode was observed under stereo microscope and recorded. The mean shear bond strength for each group was analyzed with SPSS 19.0 software ANOVA method. The surface morphology of each material was observed after setting and acid treatment under scanning electron microscope.@*RESULTS@#There was no significant difference among the three tested materials at either initial setting point or 7 d after application (P<0.05). The bond strength of MTA was significantly higher than those of BP and FS 24 h after application in both bonding modes (P<0.05). For all the three tested materials, shear bond strength was significantly higher for complete setting group than for initial setting group of the same material (P<0.05). Under scanning electron microscope, the characteristic crystal patterns could be observed on the three bioactive materials surfaces after complete setting, the size of which was bigger for MTA than for BP and FS. These features were lost to some extent after self-etch primer application or phosphoric acid etching.@*CONCLUSION@#Based on the present results, adequate bond strength can be obtained for FS at initial setting time, which is comparable with BP and MTA. This implies that clinically composite restoration can be placed over bioactive direct capping materials after shortened initial setting process in one visit.

[The effects of dioscin on myocardial contraction and sodium-cal-cium exchanger].

OBJECTIVE: To investigate the inotropic effects of dioscin (Dio)in rat isolated-heart and intracellular free calcium concentration in isolated rat ventricular myocytes and to explore its mechanism preliminarily. METHODS: Left ventricle contractile function was measured using the Langendorff non-recirculating mode of isolated rat heart perfusion. Effects of dioscin and dioscin+SEA0400, sodium-calcium exchanger (NCX) inhibitor, were investigated by measuring left ventricular systolic pressure (LVSP) and left ventricular end diastolic pressure (LVEDP). Also, heart rate (HR), peak rate of rise/fall of left ventricular pressure (±dp/dtmax) of isolated rat heart were calculated; Effects of dioscin and SEA0400 on intracellular free calcium concentration in rat H9c2 cells were measured by Fluo3-AM and then detected the fluorescence intensity with confocal microscopy. RESULTS: With 1 µmol/L dioscin, LVSP was significantly increased by 19.7% (P<0.01) and dp/dtmax was increased by 9.6%; With 1 µmol/L dioscin, the relative fluorescence intensity of intracellular free calcium concentrations were strong significantly(P<0.01). While in presence of SEA0400, the relative fluorescence intensity was changed to 17.09±0.63 (P<0.01) by 1 µmol/L dioscin. With 1 µmol/L dioscin, the relative fluorescence intensity was weak(P<0.01) without calcium or sodium in the extracellular fluid. CONCLUSIONS: Dioscin shows positive inotropic effect on isolated rat heart, enhancing the LVSP and +dp/dtmax; Dioscin increases the intracellular concentration of Ca2+ in the cardiac myocytes by increasing Na+ influx and facilitating the reverse mode of the sodium-calcium exchanger.

Effect of pathological fracture on the prognosis of patients with limb osteosarcoma: A meta-analysis / 肿瘤

Objective: To evaluate the effect of pathological fracture on the prognosis of patients with limb osteosarcoma. Methods: A computer-based online search was performed by using EMBASE, Cochrane Library, PubMed, CNKI (China National Knowledge Infrastructure), Wanfang database, VIP database and Chinese Biomedical Literature Database. Relevant studies on clinical outcome of limb osteosarcoma patients with pathological fracture vs without pathological fracture were collected and the quality of the studies were assessed using Newcastle-Ottawa Scale. The data of the studies were abstracted. Meta-analysis was performed using Stata 12.0 software. Results: Ten studies of 2604 cases entered the Meta-analysis, including 356 cases of osteosarcoma with pathological fracture (study group) and 2248 cases of osteosarcoma without pathological fracture (control group). This Meta-analysis revealed that the patients in the study group had poor three-year overall survival (OS) [odds ratio (OR) = 2.57, 95% confidence Interval (CI): 1.54-4.29; P = 0.000) and five-year OS (OR = 1.57, 95% CI: 1.05-2.34; P = 0.029) than those in the control group. Furthermore, there were significant differences in three-year event-free survival (EFS) (OR = 1.87, 95% CI: 1.21-2.87; P = 0.005) and five-year EFS (OR = 1.52, 95% CI: 1.16-1.99; P = 0.002) between the study group and control group. No significant difference was found in the rate of local recurrence between the two groups (P > 0.05), and there was also no significant difference in the rate of local recurrence between patients who were treated with amputation and limb salvage in pathological fracture subgroup (P > 0.05). Conclusion: This meta-analysis suggests that the prognosis of limb osteosarcoma patients with pathological fracture is more worse than that of the patients without pathological fracture. There is no higher risk in the rate of local recurrence after limb salvage in patients with pathological fracture.

Expression and clinical signiifcance of PAK5 protein expression in osteosarcoma / 中国癌症杂志

Background and purpose: p21-activated kinase 5 (PAK5) is a recently identified member of PAKs that regulate many intracellular processes such as cytoskeleton remodeling, cell proliferation, cell differentiation, gene transcription and cell apoptosis. Recently, studies found that PAK5 was overexpressed in some cancer such as gastric and colon cancer. However, the expression status and biological function of PAK5 in osteosarcoma are not clearly known. The objective of this study was to investigate the expression of PAK5 in osteosarcoma tissue and their relationships with the prognosis of osteosarcoma. Methods: The expression of PAK5 was detected by using immunohistochemical method in 92 specimens of human osteosarcoma tissues and 33 cases of osteoclastoma tissue, respectively. Results: The positive rate of PAK5 was 71.7% (66/92) in all the 92 cases of osteosarcoma. PAK5 expressions were not related to clinical variables such as gender, age, tumor location, tumor size, histological type and local recurrence, but signiifcantly related to Enneking grade, tumor cell necrosis rate and lung metastasis, and the high expression of PAK5 may reduce the efifciency of chemotherapy. Survival analysis indicated that high expression of PAK5 correlated with poor prognosis of patients with osteosarcoma. Univariate survival analysis showed that the signiifcant prognostic factors were tumor size, Enneking grade, local recurrence, lung metastasis and expression levels of PAK5. COX multivariate regression identified that the PAK5 expression levels (P=0.001) and lung metastasis (P=0.015) were independent prognostic factors of patients with osteosarcoma. Conclusion:The positive expressions of PAK5 closely correlate with Enneking grade, tumor cell necrosis rate and lung metastasis. Detection of PAK5 may be used as a molecular marker for prognosis of osteosarcoma. The high expression of PAK5 may reduce the efifciency of chemotherapy.

The durability of three self-etch adhesives bonded to dentin / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the durability of self-etch adhesives bonded to dentin in vitro.</p><p><b>METHODS</b>Forty-two extracted human molars were selected and occlusal dentin surfaces were exposed. The teeth were randomly distributed into three groups based on adhesives applied. The one-step self-etch adhesive B(Adper Prompt) and C(G-Bond) and two-step self-etch adhesive A (Clearfil SE bond) were used. After application of the adhesives to the dentin surfaces, composite crowns were built up, after 24 h water storage, the teeth were sectioned longitudinally into sticks (1.0 mm×1.0 mm bonding area) for microtensile testing or slabs (1 mm thick) for scanning electron microscopec (SEM) observation. Bonding strength (mTBS) and nano-leakage were evaluated immediately after cutting or after 6 months in water. The mTBS was analyzed using one-way ANOVA (SPSS 13.0). The nanoleakage was observed by SEM with a backscattered electron detector.</p><p><b>RESULTS</b>Both adhesives and water storage time affected the mTBS. All adhesives showed decreased bond strength after six-month water aging [A dropped from (40.60 ± 5.76) MPa to (36.04 ± 3.15) MPa; B dropped from (19.06 ± 1.50) MPa to (11.19 ± 1.97) MPa; C dropped from (17.75 ± 1.10) MPa to (9.14 ± 1.15) MPa] (P < 0.05). B and C showed lower mTBS than A after aging (P < 0.05). Compared to A, nanoleakage was more obvious after aging for B and C.</p><p><b>CONCLUSIONS</b>All self-etch adhesives tested were probably influenced by water aging, however, the two-step adhesive showed better durability than the one-step adhesives.</p>