Objective·To compare the effects of calcium hydroxide(CH)residues in root canals and root canal filling methods on apical closure,and to provide reference for clinical selection of root canal sealing drugs and filling methods.Methods·Seventy-five permanent mandibular premolar teeth with single root canals that were extracted due to orthodontic treatment or periodontal problems were collected from the Department of Oral and Maxillofacial Surgery of the Affiliated Hospital of Qingdao University.The crowns were removed,the root canals were prepared,and the specimens were randomly assigned into 3 groups:a water-soluble calcium hydroxide group(Group A,n=30),an oil-soluble calcium hydroxide group(Group B,n=30),and an unsealed control group(Group C,n=15).After 2 weeks of sealing,Groups A and B underwent manual preparation with a#35 K-file,followed by ultrasonic agitation and irrigation of the root canal to ensure that the calcium hydroxide residue was located roughly at the root apex and that the residue was 15%to 20%.Groups A,B,and C were randomly divided into 3 groups:the iRoot SP single-tip group(Group 1),the hot compression group(Group 2),and the cold compression group(Group 3),and root canals were filled using the iRoot SP single-tip method,the hot adhesive vertical compression filling method,and the cold adhesive lateral compression filling method,respectively.A dye penetration test was used to evaluate apical microleakage,and scanning electron microscopy was used to observe the microscopic morphology of the dentin-root canal sealer interface in each group.Statistical analysis was performed using two-way ANOVA.Results·Both root canal sealing drugs and root canal filling methods affected the apical sealing,and there was an interaction between them.The effects of residual calcium hydroxide on apical closure were analyzed.The difference between Group B and Group C was statistically significant only in Group 1.There were statistically significant differences between Group A and Group C in Group 2 and Group 3,and statistically significant differences between Group A and Group B regardless of the root filling method.Among the three root filling methods,there was a statistically significant difference between Group 1 and Group 3 in Group C(P=0.013).In Group A and Group B,there were statistically significant differences between Group 2,Group 3 and Group 1(P<0.001).Conclusion·The residual water-soluble calcium hydroxide in the root canal has a negative effect on the apical closure,but the residual oil-soluble calcium hydroxide has a small negative effect on the apical closure.iRoot SP can reduce the negative effect of residual water-soluble calcium hydroxide on root canal closure.

Background and purpose:The aberrant activation of pyruvate dehydrogenase kinase 1(PDK1)drives tumor microenvironment remodeling and metastasis through mediating the Warburg effect.As a critical tumor-suppressive phosphatase,phosphatase and tensin homolog deleted on chromoseme ten(PTEN)activates PDK1 via loss of expression to induce aerobic glycolysis and accelerate tumor progression.The molecular interplay between PDK1 and PTEN in kidney renal clear cell carcinoma(KIRC)urgently requires systematic elucidation.This study aimed to clarify how PTEN regulates PDK1 to inhibit malignant phenotypes in KIRC.Methods:Bioinformatics analysis was conducted to compare PTEN and PDK1 expression levels as well as their prognostic correlations in the Cancer Genome Atlas(TCGA)-KIRC datasets.KIRC cell models was established by either silencing PDK1 or enhancing its expression,subsequently evaluating their malignancy characteristics through cell counting kit-8(CCK-8)proliferation,colony formation,cell migration,and invasion assays.To validate the regulatory interactions,we used PDK1-overexpressing cells treated with a PTEN-specific inhibitor.Western blot was used to dectect the protein expression.Results:The TCGA-KIRC analysis found significantly higher mRNA levels of PTEN and PDK1 in tumor tissues compared to normal controls(P＜0.05),yet this high expression was associated with improved overall survival(P＜0.01).Besides,a strong positive correlation was observed between PTEN and PDK1 expressions(r=0.52,P＜0.001).Functional assays demonstrated that PDK1 knockdown markedly promoted cell proliferation,migration,and invasion,whereas PDK1 overexpression exhibited opposing effects.Mechanistically,inhibiting PTEN worsened malignant behaviors(P＜0.01),however,these effects were reversed by overexpressing PDK1.Conclusion:This study presents the first evidence of the dual tumor-suppressive function of the PTEN-PDK1 biological axis in renal cancer,which supports the development of precision treatment strategies based on novel targets.

Objective·To compare the effects of calcium hydroxide(CH)residues in root canals and root canal filling methods on apical closure,and to provide reference for clinical selection of root canal sealing drugs and filling methods.Methods·Seventy-five permanent mandibular premolar teeth with single root canals that were extracted due to orthodontic treatment or periodontal problems were collected from the Department of Oral and Maxillofacial Surgery of the Affiliated Hospital of Qingdao University.The crowns were removed,the root canals were prepared,and the specimens were randomly assigned into 3 groups:a water-soluble calcium hydroxide group(Group A,n=30),an oil-soluble calcium hydroxide group(Group B,n=30),and an unsealed control group(Group C,n=15).After 2 weeks of sealing,Groups A and B underwent manual preparation with a#35 K-file,followed by ultrasonic agitation and irrigation of the root canal to ensure that the calcium hydroxide residue was located roughly at the root apex and that the residue was 15%to 20%.Groups A,B,and C were randomly divided into 3 groups:the iRoot SP single-tip group(Group 1),the hot compression group(Group 2),and the cold compression group(Group 3),and root canals were filled using the iRoot SP single-tip method,the hot adhesive vertical compression filling method,and the cold adhesive lateral compression filling method,respectively.A dye penetration test was used to evaluate apical microleakage,and scanning electron microscopy was used to observe the microscopic morphology of the dentin-root canal sealer interface in each group.Statistical analysis was performed using two-way ANOVA.Results·Both root canal sealing drugs and root canal filling methods affected the apical sealing,and there was an interaction between them.The effects of residual calcium hydroxide on apical closure were analyzed.The difference between Group B and Group C was statistically significant only in Group 1.There were statistically significant differences between Group A and Group C in Group 2 and Group 3,and statistically significant differences between Group A and Group B regardless of the root filling method.Among the three root filling methods,there was a statistically significant difference between Group 1 and Group 3 in Group C(P=0.013).In Group A and Group B,there were statistically significant differences between Group 2,Group 3 and Group 1(P<0.001).Conclusion·The residual water-soluble calcium hydroxide in the root canal has a negative effect on the apical closure,but the residual oil-soluble calcium hydroxide has a small negative effect on the apical closure.iRoot SP can reduce the negative effect of residual water-soluble calcium hydroxide on root canal closure.

Background and purpose:The aberrant activation of pyruvate dehydrogenase kinase 1(PDK1)drives tumor microenvironment remodeling and metastasis through mediating the Warburg effect.As a critical tumor-suppressive phosphatase,phosphatase and tensin homolog deleted on chromoseme ten(PTEN)activates PDK1 via loss of expression to induce aerobic glycolysis and accelerate tumor progression.The molecular interplay between PDK1 and PTEN in kidney renal clear cell carcinoma(KIRC)urgently requires systematic elucidation.This study aimed to clarify how PTEN regulates PDK1 to inhibit malignant phenotypes in KIRC.Methods:Bioinformatics analysis was conducted to compare PTEN and PDK1 expression levels as well as their prognostic correlations in the Cancer Genome Atlas(TCGA)-KIRC datasets.KIRC cell models was established by either silencing PDK1 or enhancing its expression,subsequently evaluating their malignancy characteristics through cell counting kit-8(CCK-8)proliferation,colony formation,cell migration,and invasion assays.To validate the regulatory interactions,we used PDK1-overexpressing cells treated with a PTEN-specific inhibitor.Western blot was used to dectect the protein expression.Results:The TCGA-KIRC analysis found significantly higher mRNA levels of PTEN and PDK1 in tumor tissues compared to normal controls(P＜0.05),yet this high expression was associated with improved overall survival(P＜0.01).Besides,a strong positive correlation was observed between PTEN and PDK1 expressions(r=0.52,P＜0.001).Functional assays demonstrated that PDK1 knockdown markedly promoted cell proliferation,migration,and invasion,whereas PDK1 overexpression exhibited opposing effects.Mechanistically,inhibiting PTEN worsened malignant behaviors(P＜0.01),however,these effects were reversed by overexpressing PDK1.Conclusion:This study presents the first evidence of the dual tumor-suppressive function of the PTEN-PDK1 biological axis in renal cancer,which supports the development of precision treatment strategies based on novel targets.

Objective:To establish a carbohydrate metabolism-related genes(CRGs)prognostic model for clear cell renal cell carcinoma(ccRCC)and investigate its clinical value.Methods:ccRCC mRNA expression data were sourced from The Cancer Genome Atlas(TCGA)data-base.CRGs were retrieved from the MSigDB and KEGG databases.A prognostic model based on CRGs was constructed using the LASSO lin-ear regression model,and the risk score(RS)was calculated.Patients were assigned into high-and low-risk groups according to the median RS.Differences in survival,immune infiltration,mutation,and immune response between the two groups were analyzed using Kaplan-Meier curves and bioinformatics methods.Constructing a nomogram based on the RS and clinical features and validating its accuracy of prognostic predictions.The expression of CRGs in the ccRCC samples was detected using RT-qPCR.Results:A total of eight key genes were utilized to construct a prognostic risk model for ccRCC.Survival analysis revealed that patients in the low-risk group had a better prognosis(P<0.001).Bioinformatics analysis showed that the RS correlated with immune cell infiltration,mutation,and immune responses.The nomogram based on the RS and clinical features demonstrated a strong predictive ability for prognosis.In vitro experiments confirmed notable differences in the expression of the eight CRGs between ccRCC and adjacent non-malignant tissues.Conclusions:A prognostic model based on CRGs can effectively predict the prognosis of patients with ccRCC.

Objective: To compare the efficiency of four methods that remove calcium hydroxide in root canals and to guide clinical practice. Methods : Sixty-five isolated mandibular single root canal premolars were collected. After crown cutting and root canal preparation, a tooth was randomly selected as the blank control group, and the remaining 64 teeth were equally divided into Groups A and B (n = 32). Group A was injected with water-soluble calcium hydroxide, and Group B was injected with oil-soluble calcium hydroxide. After 2 weeks of drug sealing, Groups A and B were randomly divided into 4 groups (n = 8), including the lateral opening syringe group, sonic vibration group, ultrasonic group, and Er: YAG laser group. Before and after calcium hydroxide removal, the samples were scanned by cone-beam CT, and the data were imported into Mimics for 3D reconstruction. The root canal was divided into the following segments: superior root segment, middle and apical, and the calcium hydroxide volume of each segment of the root canal was calculated. The volumes of calcium hydroxide before and after removal were V1 and V2, respectively, with a clearance rate = (V1-V2)/V1×100%. Three-factor ANOVA was used for statistical analysis. After Groups A and B were reconstructed, the apical region with residual calcium hydroxide was selected, and the blank control was observed by scanning electron microscopy (SEM). Results : Two types of calcium hydroxide could not be completely removed by the four flushing methods. The clearance rate of water-soluble calcium hydroxide was higher than that of oil-soluble calcium hydroxide (P<0.001). Among the three segments of the root canal, the clearance rate of the apical segment was lower (P<0.05). The Er: YAG laser treatment group showed the highest removal efficiency of two kinds of calcium hydroxide, which was higher than that of the other groups, especially in apical of the root. Compared with the sonic wave washing group and the syringe washing group, the ultrasonic wave washing group exhibited significant advantages (P<0.05). The clearance rate of the sonic wave washing group was higher in the oily calcium hydroxide root middle group than in the syringe washing group (P<0.05). SEM showed that the two kinds of calcium hydroxide could not be completely removed, but the residual rate of oil-soluble calcium hydroxide was large. Conclusion Both types of calcium hydroxide could not be completely removed, and compared to water-soluble calcium hydroxide, oil-soluble calcium hydroxide was more difficult to remove. Among the four cleaning methods, Er:YAG laser swing washing showed the higher cleaning efficiency.

Objective:To explore the effect of dose adjustment based on doxofylline blood concentration monitoring on safety of combination of doxofylline and terbutaline for respiratory diseases.Methods:The subjects were selected from patients who received doxofylline injection, terbutaline sulphate solution for nebulizationor, and the combination of the two drugs and hospitalized in Department of Respiratory Medicine of Zhengzhou Second People′s Hospital from January 1, 2014 to December 31, 2018. Patients who met the inclusion criteria were divided into 3 groups: doxofylline group, terbutaline group, and combination of doxofylline and terbutaline group (combination group). All patients in the 3 groups were given conventional treatments and symptomatic treatments. Doxofylline 300 mg once daily was given by an IV infusion and terbutaline 2 ml (5 mg) thrice daily was given by atomized inhalation for 7-14 days. Adverse reactions in the 3 groups were compared. The dosage of doxofylline in patients with adverse reactions of grade 1 was adjusted to 250 mg once daily, 200 mg once daily for patients with adverse reactions of grade 2, and doxofylline was stopped in patients with adverse reactions of more than grade 3. The blood concentration of doxofylline, the proportion of the patients whose adverse reactions were alleviated or disappeared, the length of hospital stay, and the efficiency of treatment before and after dose adjustment of doxofylline in patients in the doxofylline group and the combination group were compared.Results:A total of 6 582 patients were entered in the study. Of them, 1 438 patients were in the doxofylline group, including 793 males and 645 females with age of (61±11) years; 2 217 patients were in the terbutaline group, including 1 281 males and 936 females with age of (60±15) years; 2 927 patients were in the combination group, including 1 644 males and 1 283 females with age of (63±12) years. The differences in gender, age distribution, basic disease, combined disease, and combination medication among the 3 groups were not statistically significant ( P>0.05). The overall incidences of adverse reactions in the 3 groups were 13.1% (189/1 438), 8.9% (197/2 217), and 21.2% (620/2 927), respectively, which was higher in the combination group than that in the doxofylline group ( χ 2=41.271, P<0.001) and the terbutaline group ( χ 2=142.766, P<0.001) and higher in the doxofylline group than that in the terbutaline group ( χ 2=16.738, P<0.001). The incidences of tremor and headache in the combination group were higher than those in the other 2 groups( P<0.001), the incidence of hyperglycemia was higher than that in the doxofylline group( P=0.003), the incidence of insomnia was higher than that in the terbutaline group( P<0.001), the incidence of tachycardia was higher than that in the terbutaline group( P<0.001), the incidence of nausea was lower than that in the doxofylline group( P<0.001) and higher than that in the terbutaline group( P<0.001), the incidence of mood disorders was higher than that in terbutaline group ( P=0.017). No adverse reactions of more than grade 3 occurred in the 3 groups, the difference in proportions of patients with adverse reactions of grade 1 and grade 2 was not statistically significant( χ 2=1.097, P=0.578). The difference in blood concentration of doxofylline in patients with adverse reactions between the combination group and the doxofylline group was not statistically significant before dose adjustment ( P>0.05), but all decreased after dose adjustment (all P<0.001) and the blood concentration of doxofylline in the combination group was lower than that in the doxofyllin group [(8.38±2.19) μg/ml) vs. (10.64±2.55) μg/ml, P<0.001]; the proportion of patients whose adverse reactions were alleviated or disappeared in the combination group was higher than that in the doxofylline group [40.81% (253/620) vs. 30.16% (57/189), P=0.008], the hospitalization time was shorter than that in the doxofylline group [(10±2) d vs. (15±3) d, P<0.001], the treatment efficiency was higher than that in the doxofylline group [531 (85.65%) vs. 136 (71.96%), P<0.001]. Conclusion:When doxofylline injection is combined with terbutaline solution for nebulizationor, the blood concentration of doxofylline can be controlled at (8.38±2.19) μg/ml by monitoring the blood concentration of doxofylline, which can not only improve the treatment efficacy, but also improve the medication safety.

Objective:To explore the effect of dose adjustment based on doxofylline blood concentration monitoring on safety of combination of doxofylline and terbutaline for respiratory diseases.Methods:The subjects were selected from patients who received doxofylline injection, terbutaline sulphate solution for nebulizationor, and the combination of the two drugs and hospitalized in Department of Respiratory Medicine of Zhengzhou Second People′s Hospital from January 1, 2014 to December 31, 2018. Patients who met the inclusion criteria were divided into 3 groups: doxofylline group, terbutaline group, and combination of doxofylline and terbutaline group (combination group). All patients in the 3 groups were given conventional treatments and symptomatic treatments. Doxofylline 300 mg once daily was given by an IV infusion and terbutaline 2 ml (5 mg) thrice daily was given by atomized inhalation for 7-14 days. Adverse reactions in the 3 groups were compared. The dosage of doxofylline in patients with adverse reactions of grade 1 was adjusted to 250 mg once daily, 200 mg once daily for patients with adverse reactions of grade 2, and doxofylline was stopped in patients with adverse reactions of more than grade 3. The blood concentration of doxofylline, the proportion of the patients whose adverse reactions were alleviated or disappeared, the length of hospital stay, and the efficiency of treatment before and after dose adjustment of doxofylline in patients in the doxofylline group and the combination group were compared.Results:A total of 6 582 patients were entered in the study. Of them, 1 438 patients were in the doxofylline group, including 793 males and 645 females with age of (61±11) years; 2 217 patients were in the terbutaline group, including 1 281 males and 936 females with age of (60±15) years; 2 927 patients were in the combination group, including 1 644 males and 1 283 females with age of (63±12) years. The differences in gender, age distribution, basic disease, combined disease, and combination medication among the 3 groups were not statistically significant ( P>0.05). The overall incidences of adverse reactions in the 3 groups were 13.1% (189/1 438), 8.9% (197/2 217), and 21.2% (620/2 927), respectively, which was higher in the combination group than that in the doxofylline group ( χ 2=41.271, P<0.001) and the terbutaline group ( χ 2=142.766, P<0.001) and higher in the doxofylline group than that in the terbutaline group ( χ 2=16.738, P<0.001). The incidences of tremor and headache in the combination group were higher than those in the other 2 groups( P<0.001), the incidence of hyperglycemia was higher than that in the doxofylline group( P=0.003), the incidence of insomnia was higher than that in the terbutaline group( P<0.001), the incidence of tachycardia was higher than that in the terbutaline group( P<0.001), the incidence of nausea was lower than that in the doxofylline group( P<0.001) and higher than that in the terbutaline group( P<0.001), the incidence of mood disorders was higher than that in terbutaline group ( P=0.017). No adverse reactions of more than grade 3 occurred in the 3 groups, the difference in proportions of patients with adverse reactions of grade 1 and grade 2 was not statistically significant( χ 2=1.097, P=0.578). The difference in blood concentration of doxofylline in patients with adverse reactions between the combination group and the doxofylline group was not statistically significant before dose adjustment ( P>0.05), but all decreased after dose adjustment (all P<0.001) and the blood concentration of doxofylline in the combination group was lower than that in the doxofyllin group [(8.38±2.19) μg/ml) vs. (10.64±2.55) μg/ml, P<0.001]; the proportion of patients whose adverse reactions were alleviated or disappeared in the combination group was higher than that in the doxofylline group [40.81% (253/620) vs. 30.16% (57/189), P=0.008], the hospitalization time was shorter than that in the doxofylline group [(10±2) d vs. (15±3) d, P<0.001], the treatment efficiency was higher than that in the doxofylline group [531 (85.65%) vs. 136 (71.96%), P<0.001]. Conclusion:When doxofylline injection is combined with terbutaline solution for nebulizationor, the blood concentration of doxofylline can be controlled at (8.38±2.19) μg/ml by monitoring the blood concentration of doxofylline, which can not only improve the treatment efficacy, but also improve the medication safety.

Objective: To investigate the modification of the classic techniques of total auricle reconstruction with skin expansion, and its clinical application. Methods: We performed three-dimensional measurement of the normal auricle and the expanded flap on 150 microtia patients. According to the data, we carried out total auricle reconstruction using extended postauricle expanded flap techniques for 82 patients of the group. Firstly, a 50 ml kidney-shaped expander was inserted subcutaneously in the mastoid region. Approximately 65 ml saline was injected in about 30 days, and expansion was kept without injection for another 30 days. In the second stage, we removed the expander and dissected the scalp 4-5 cm around the expanded skin, to make a composite flap consisted of expanded skin and extend scalp. Then we used the flap to encapsulate the three-dimensional rib cartilage framework to accomplish total auricle reconstruction. Results: The blood supply and venous drainage of the flap was good. No obvious postoperative flap swelling was observed. Only 2 cases of helix skin necrosis happened in 48 hours after operation. Small area of skin defect was treated by debridement and suture, while larger area of skin defect was repaired with postauricular fascia flap and free skin graft. Postoperative follow-up period was 4-15 months, about 6.7 months in average. Bilateral ear size and position were similar with clear structures and shapes. Helix seemed more slim, auriculocephalic sulcus was obvious, auriculocephalic angle was similar to the other side. There was no color abberration between the front and back side of reconstructed ear. Scars of retroauricular hairline incision and costal cartilage harvesting incision were not obvious. Conclusions The novel surgical techniques is reasonable and simple without fascia flap or skin graft, which is worthy of application by more plastic surgeons.

Objective:To evaluate the effect of semiconductor lasers irradiation after routine root canal preparation on root cannal seal.Methods:60 Single-rooted freshly extracted human teeth were randomly divided into 6 groups(n=10).The crowns were removed at the cementoenamel junction and the roots were endodontically prepared with conventional methods.The roots in groups A and B were irradiated with 1 W semiconductor laser for 20 s,in group C and D were ultrasonically washed for 1 min,in group E and F without any treatment were used as the controls.Then all the roots were filled by vertical condensation of warm gutta-percha.The root cannal seal was evaluated with microleakage measurement.The data was analyzed by ANOVA.The teeth of group B,D and F were sectioned and examined under scanning electron microscope(SEM).Results:The microleakage(mm) of group A,C and E was 1.70±0.82,2.02±0.40 and 4.56±2.72 respectively(A vs E,P<0.01;C vs E,P<0.05;A vs C,P>0.05).SEM observation showed the melting,narrowness or closure of most dentinal tubules in group B,past and/or gutta-percha in the most dentinal tubules of group D.Conclusion:Semiconductor laser irradiation prior to root cannal filling can promote the effects of cannal seal.