BACKGROUND:Clear aligners,due to their special material properties,are more prone to the"roller coaster effect"during the process of extracting the maxillary first premolar and closing the gap by retracting the anterior teeth,tilting and moving the teeth,leading to deepening of the anterior overjet and opening of the posterior teeth.There are fewer related studies at present concerning whether the thickness or stiffness of the aligner can be changed to reduce the"roller coaster effect"and better control the orthodontic tooth movement,.OBJECTIVE:To analyze the differences in tooth movement control ability of clear aligners of different thicknesses and stiffness when internally retracting maxillary anterior teeth by means of the three-dimensional finite element method.METHODS:Cone beam CT data of patients with convex profile were imported into Mimics and other software to simulate clinical cases.Three-dimensional finite element models were constructed to remove the first premolars,including the maxilla,teeth,and periodontal ligaments,while the diaphragms of clear aligners with thicknesses of 0.50 mm and 0.75 mm were assembled.Four sets of working conditions were created by loading the material properties of two Young's modulus of 1 000 MPa and 2 000 MPa.According to the clinical design to close of the extraction gap,and analyze the distribution of periodontal ligament stress,the displacement trend and the initial displacement of the teeth after loading and calculating in Workbench 2023 R1 software.RESULTS AND CONCLUSION:(1)The Von-Mises stress distribution pattern of periodontal ligament was consistent among the four working conditions,with the maximum value mainly distributed at the cervical part of teeth.The thicker diaphragm of the aligner,the higher the Von-Mises stress;the higher Young's modulus of the aligner,the higher the Von-Mises stress.(2)Under the four working conditions,the overall displacement trend of the maxillary dentition was that the crowns of the anterior teeth moved towards the lingual side and the roots towards the labial side,while the crowns of the posterior teeth moved towards the proximal-medial side and the roots towards the distal-medial side,and it was observed that the crown-root displacements of the teeth were in the opposite direction in all the conditions,and that the displacement of the crowns was greater than the displacement of the roots.Except for canines,the thicker the aligner diaphragm,the lower the R/C value(root-crown displacement ratio);the higher the modulus of elasticity of the aligner diaphragm,the lower the R/C value.(3)The results showed that when the maxillary anterior teeth were internally retracted using invisible aligners,the teeth showed a tendency to tilt and move without incisor torque compensation being designed;the greater the thickness of the aligner and the elastic modulus,the greater the control of the teeth,and the tendency of the teeth to tilt and move decreased;and the cuspids had to be controlled by other auxiliary means.

Objective To observe the clinical efficacy of belimumab combined with glucocorticoids in the treatment of children with systemic lupus erythematosus(SLE).Methods A total of 64 children with SLE were randomly divided into the observation group and the control group,with 32 cases in each group.The control group was treated with oral prednisone tablets combined with hydroxychloroquine sulfate tablets,while the observation group was treated with belimumab on the basis of treatment in the control group.After 6 months of treatment,the clinical efficacy,systemic lupus erythematosus disease activity index(SLEDAI)scores and laboratory indicators[complement C3,complement C4,immunoglobulin IgG(IgG),B lymphocytes,white blood cell count(WBC),erythrocyte sedimentation rate(ESR),serum C-reactive protein(CRP),24-hour urine protein quantification(24 h UP),serum creatinine(SCr)and blood urea nitrogen(BUN)]were compared between the two groups.Results After 6 months of treatment,the total effective rate was higher in the observation group than that of the control group(93.8%vs.75.0%,P＜0.05).Compared with before treatment,both groups showed lower SLEDAI scores,IgG,B lymphocytes,ESR,CRP,SCr,24 h UP and BUN after treatment,while C3,C4 levels and WBC were higher.Moreover,the improvement of all indicators was better in the observation group than that in the control group(P＜0.05).Conclusion Belimumab combined with glucocorticoids can improve the clinical efficacy,control disease activity and enhance immune function in children with SLE.

Objective:To assess the efficacy and safety of Tacrolimus（TAC）in combination with glucocorticosteroid（GC）for treating IgA vasculitis nephritis（IgAVN）in children.Methods:A retrospective analysis was conducted on pediatric patients who were diagnosed with IgAVN from January 2015 to January 2022 in Children's Hospital of Hebei Province.The patients presented with nephrotic-range proteinuria or persistent urine protein（>0.5g/24 h）despite adequate glucocorticoid and other treatments in patients who do not reach massive proteinuria levels.They were treated with TAC combined with GC. The following laboratory parameters were obtained for outcome assessment: 24-hour urinary protein excretion, serum albumin, serum creatinine levels, and fasting blood glucose measurements. The efficacy and adverse reactions of TAC were summarized.Results:A total of 97 children (55 males and 42 females) were included. The average age of diagnosis of IgA vasculitis was (8.65±2.46) years, and 95.9% of the children developed renal involvement within 30 days after diagnosis. Pathological examination of renal puncture: 5 cases of grade Ⅱa, 2 cases of grade Ⅱb, 31 cases of grade Ⅲa, 57 cases of grade Ⅲb, and 2 cases of grade Ⅳb.Remission rate at 3 months was 96.9%（94/97）.Three patients failed to achieve clinical remission who were treaed with other immunosuppressants.After 1, 3, 6 and 12 months of TAC treatment, the urine protein levels of 94 children were lower than those before treatment, and the differences were statistically significant ( P < 0.05), showing a gradual downward trend. Serum albumin levels were higher than those before treatment, and the differences were statistically significant ( P < 0.05), showing a gradual upward trend.After 3 months and 6 months of TAC treatment, the serum creatinine and fasting blood glucose of the children increased. With the remission of the disease, TAC dosage decreased, the mean values of serum creatinine and fasting blood glucose decreased after 12 months of treatment.The average treatment time of TAC was (10.8±2.6) months, the average follow-up time was (3.33±1.56) years, and the longest follow-up time was 8 years. During the follow-up period, there were no serious adverse reactions such as gastrointestinal discomfort, liver function damage and severe infection. After stopping GC and TAC treatment, 80 children got sustained remission. Conclusion:The combination of TAC and GC has been proved to be effective in treating IgAVN in children.The overall effective rate is high,and clinical remission can be achieved quickly with relatively mild adverse reactions.

Objective To investigate the effects and molecular mechanisms of regenerating islet-derived 3-Alpha(REG3A)on the proliferation,apoptosis and cisplatin(DDP)resistance of ovarian cancer(OC)cells.Methods Cancer tissue and adjacent tissue samples of 97 ovarian cancer patients admitted to Qinghai Fifth People's Hospital from January 2021 to December 2022 were collected.Quantitative reverse transcriptase-mediated PCR(qRT-PCR)and immunohis to chemistry(IHC)were used to detect the expression of REG3A in cancer tissues and adjacent tissues,and the relationship between its expression and the clinical pathological characteristics and prognosis of patients was analyzed.QRT-PCR was used to detect the expression of REG3A in human normal ovarian epithelial cell line OSE and human OC cell lines(ES2,HEY,A2780,and SKOV3).SKOV3 and DDP resistant OC cell lines(SKOV3/DDP)were selected and randomly divided into siNC group and siREG3A group.Cell counting kit-8(CCK-8)was used to detect cell proliferation activity.Determination of cell drug resistance by methylthiazolyl tetrazolium(MTT).Flow cytometry was used to detect proliferation cycle and apoptosis.Immunoblotting was used to detect the expression of resistance,proliferation,apoptosis and phsphatidylinostol 3-kinase(PI3K)/protein kinase B(Akt)pathway related proteins in OC cells.Results The expression of REG3A mRNA in ovarian cancer tissues was higher than that in adjacent tissues(1.46±0.43 vs 0.52±0.11),and the difference was statistically significant(t=20.858,P<0.001).The 5-year survival rate of patients with high expression of REG3A was 24.49%(12/49),which was lower than the 91.67%(44/48)of patients with low expression of REG3A,and the difference was statistically significant(χ2=44.841,P<0.001).The proportion of patients with FIGO stages III-IV,moderate to high differentiation and tumor size>3cm in the high expression group of REG3A was higher than that in the low expression group of REG3A,and the differences were statistically significant(χ2=4.537～9.972,all P<0.05).Compared with OSE,the mRNA and protein expression of REG3A in ES2,HKY,A2780 and SKOV3 increased significantly(t=6.725～30.234,all P<0.01).Compared with the siNC group,the expression of REG3A was downregulated in SKOV3 cells in the siREG3A group(0.23±0.02 vs 0.99±0.06),cell activity decreased at 24,48 and 72 hours of transfection,the proportion of G1 phase cells increased,while the proportion of S and G2 phase cells and apoptosis rate,MDR-1,Cyclin D1 and Cleaved caspase 3 protein expression,p-PI3K/PI3K and p-Akt/Akt ratios were decreased,and the differences were statistically significant(t=6.584～22.730,all P<0.01).After treatment with DDP at concentrations of 1.25,2.5,5,7.5 and 15 μg/ml,compared with the siNC group,the survival rates of SKOV3 and SKOV3/DDP cells in the siREG3A group gradually decreased,and the differences were statistically significant(t=2.888～11.135,all P<0.05).Conclusion REG3A is highly expressed in OC tissues and is associated with malignant progression and poor prognosis of OC.Its up-regulation promotes cancer cell proliferation and DDP resistance by activating the PI3K/Akt pathway,and inhibits apoptosis.

Objective To investigate the effects and molecular mechanisms of regenerating islet-derived 3-Alpha(REG3A)on the proliferation,apoptosis and cisplatin(DDP)resistance of ovarian cancer(OC)cells.Methods Cancer tissue and adjacent tissue samples of 97 ovarian cancer patients admitted to Qinghai Fifth People's Hospital from January 2021 to December 2022 were collected.Quantitative reverse transcriptase-mediated PCR(qRT-PCR)and immunohis to chemistry(IHC)were used to detect the expression of REG3A in cancer tissues and adjacent tissues,and the relationship between its expression and the clinical pathological characteristics and prognosis of patients was analyzed.QRT-PCR was used to detect the expression of REG3A in human normal ovarian epithelial cell line OSE and human OC cell lines(ES2,HEY,A2780,and SKOV3).SKOV3 and DDP resistant OC cell lines(SKOV3/DDP)were selected and randomly divided into siNC group and siREG3A group.Cell counting kit-8(CCK-8)was used to detect cell proliferation activity.Determination of cell drug resistance by methylthiazolyl tetrazolium(MTT).Flow cytometry was used to detect proliferation cycle and apoptosis.Immunoblotting was used to detect the expression of resistance,proliferation,apoptosis and phsphatidylinostol 3-kinase(PI3K)/protein kinase B(Akt)pathway related proteins in OC cells.Results The expression of REG3A mRNA in ovarian cancer tissues was higher than that in adjacent tissues(1.46±0.43 vs 0.52±0.11),and the difference was statistically significant(t=20.858,P<0.001).The 5-year survival rate of patients with high expression of REG3A was 24.49%(12/49),which was lower than the 91.67%(44/48)of patients with low expression of REG3A,and the difference was statistically significant(χ2=44.841,P<0.001).The proportion of patients with FIGO stages III-IV,moderate to high differentiation and tumor size>3cm in the high expression group of REG3A was higher than that in the low expression group of REG3A,and the differences were statistically significant(χ2=4.537～9.972,all P<0.05).Compared with OSE,the mRNA and protein expression of REG3A in ES2,HKY,A2780 and SKOV3 increased significantly(t=6.725～30.234,all P<0.01).Compared with the siNC group,the expression of REG3A was downregulated in SKOV3 cells in the siREG3A group(0.23±0.02 vs 0.99±0.06),cell activity decreased at 24,48 and 72 hours of transfection,the proportion of G1 phase cells increased,while the proportion of S and G2 phase cells and apoptosis rate,MDR-1,Cyclin D1 and Cleaved caspase 3 protein expression,p-PI3K/PI3K and p-Akt/Akt ratios were decreased,and the differences were statistically significant(t=6.584～22.730,all P<0.01).After treatment with DDP at concentrations of 1.25,2.5,5,7.5 and 15 μg/ml,compared with the siNC group,the survival rates of SKOV3 and SKOV3/DDP cells in the siREG3A group gradually decreased,and the differences were statistically significant(t=2.888～11.135,all P<0.05).Conclusion REG3A is highly expressed in OC tissues and is associated with malignant progression and poor prognosis of OC.Its up-regulation promotes cancer cell proliferation and DDP resistance by activating the PI3K/Akt pathway,and inhibits apoptosis.

Objective:To assess the efficacy and safety of Tacrolimus（TAC）in combination with glucocorticosteroid（GC）for treating IgA vasculitis nephritis（IgAVN）in children.Methods:A retrospective analysis was conducted on pediatric patients who were diagnosed with IgAVN from January 2015 to January 2022 in Children's Hospital of Hebei Province.The patients presented with nephrotic-range proteinuria or persistent urine protein（>0.5g/24 h）despite adequate glucocorticoid and other treatments in patients who do not reach massive proteinuria levels.They were treated with TAC combined with GC. The following laboratory parameters were obtained for outcome assessment: 24-hour urinary protein excretion, serum albumin, serum creatinine levels, and fasting blood glucose measurements. The efficacy and adverse reactions of TAC were summarized.Results:A total of 97 children (55 males and 42 females) were included. The average age of diagnosis of IgA vasculitis was (8.65±2.46) years, and 95.9% of the children developed renal involvement within 30 days after diagnosis. Pathological examination of renal puncture: 5 cases of grade Ⅱa, 2 cases of grade Ⅱb, 31 cases of grade Ⅲa, 57 cases of grade Ⅲb, and 2 cases of grade Ⅳb.Remission rate at 3 months was 96.9%（94/97）.Three patients failed to achieve clinical remission who were treaed with other immunosuppressants.After 1, 3, 6 and 12 months of TAC treatment, the urine protein levels of 94 children were lower than those before treatment, and the differences were statistically significant ( P < 0.05), showing a gradual downward trend. Serum albumin levels were higher than those before treatment, and the differences were statistically significant ( P < 0.05), showing a gradual upward trend.After 3 months and 6 months of TAC treatment, the serum creatinine and fasting blood glucose of the children increased. With the remission of the disease, TAC dosage decreased, the mean values of serum creatinine and fasting blood glucose decreased after 12 months of treatment.The average treatment time of TAC was (10.8±2.6) months, the average follow-up time was (3.33±1.56) years, and the longest follow-up time was 8 years. During the follow-up period, there were no serious adverse reactions such as gastrointestinal discomfort, liver function damage and severe infection. After stopping GC and TAC treatment, 80 children got sustained remission. Conclusion:The combination of TAC and GC has been proved to be effective in treating IgAVN in children.The overall effective rate is high,and clinical remission can be achieved quickly with relatively mild adverse reactions.

BACKGROUND:Clear aligners,due to their special material properties,are more prone to the"roller coaster effect"during the process of extracting the maxillary first premolar and closing the gap by retracting the anterior teeth,tilting and moving the teeth,leading to deepening of the anterior overjet and opening of the posterior teeth.There are fewer related studies at present concerning whether the thickness or stiffness of the aligner can be changed to reduce the"roller coaster effect"and better control the orthodontic tooth movement,.OBJECTIVE:To analyze the differences in tooth movement control ability of clear aligners of different thicknesses and stiffness when internally retracting maxillary anterior teeth by means of the three-dimensional finite element method.METHODS:Cone beam CT data of patients with convex profile were imported into Mimics and other software to simulate clinical cases.Three-dimensional finite element models were constructed to remove the first premolars,including the maxilla,teeth,and periodontal ligaments,while the diaphragms of clear aligners with thicknesses of 0.50 mm and 0.75 mm were assembled.Four sets of working conditions were created by loading the material properties of two Young's modulus of 1 000 MPa and 2 000 MPa.According to the clinical design to close of the extraction gap,and analyze the distribution of periodontal ligament stress,the displacement trend and the initial displacement of the teeth after loading and calculating in Workbench 2023 R1 software.RESULTS AND CONCLUSION:(1)The Von-Mises stress distribution pattern of periodontal ligament was consistent among the four working conditions,with the maximum value mainly distributed at the cervical part of teeth.The thicker diaphragm of the aligner,the higher the Von-Mises stress;the higher Young's modulus of the aligner,the higher the Von-Mises stress.(2)Under the four working conditions,the overall displacement trend of the maxillary dentition was that the crowns of the anterior teeth moved towards the lingual side and the roots towards the labial side,while the crowns of the posterior teeth moved towards the proximal-medial side and the roots towards the distal-medial side,and it was observed that the crown-root displacements of the teeth were in the opposite direction in all the conditions,and that the displacement of the crowns was greater than the displacement of the roots.Except for canines,the thicker the aligner diaphragm,the lower the R/C value(root-crown displacement ratio);the higher the modulus of elasticity of the aligner diaphragm,the lower the R/C value.(3)The results showed that when the maxillary anterior teeth were internally retracted using invisible aligners,the teeth showed a tendency to tilt and move without incisor torque compensation being designed;the greater the thickness of the aligner and the elastic modulus,the greater the control of the teeth,and the tendency of the teeth to tilt and move decreased;and the cuspids had to be controlled by other auxiliary means.

Objective To observe the clinical efficacy of belimumab combined with glucocorticoids in the treatment of children with systemic lupus erythematosus(SLE).Methods A total of 64 children with SLE were randomly divided into the observation group and the control group,with 32 cases in each group.The control group was treated with oral prednisone tablets combined with hydroxychloroquine sulfate tablets,while the observation group was treated with belimumab on the basis of treatment in the control group.After 6 months of treatment,the clinical efficacy,systemic lupus erythematosus disease activity index(SLEDAI)scores and laboratory indicators[complement C3,complement C4,immunoglobulin IgG(IgG),B lymphocytes,white blood cell count(WBC),erythrocyte sedimentation rate(ESR),serum C-reactive protein(CRP),24-hour urine protein quantification(24 h UP),serum creatinine(SCr)and blood urea nitrogen(BUN)]were compared between the two groups.Results After 6 months of treatment,the total effective rate was higher in the observation group than that of the control group(93.8%vs.75.0%,P＜0.05).Compared with before treatment,both groups showed lower SLEDAI scores,IgG,B lymphocytes,ESR,CRP,SCr,24 h UP and BUN after treatment,while C3,C4 levels and WBC were higher.Moreover,the improvement of all indicators was better in the observation group than that in the control group(P＜0.05).Conclusion Belimumab combined with glucocorticoids can improve the clinical efficacy,control disease activity and enhance immune function in children with SLE.

Objective To investigate the biomechanical characteristics of orthodontic tooth movement at different alveolar bone heights and provide a theoretical reference for orthodontic clinical treatment.Methods Four groups of mandibular dentition finite element models were established:the normal alveolar bone height,and 1/3,1/2,and 2/3 reductions in height.The lingual,distal,and intrusion movements of the mandibular central incisor were simulated under different loads.The distribution and variations in periodontal stress and tooth displacement were analyzed.Results Under three movements,the degree of stress concentration in the cervical area of the tooth and the periodontal equivalent force increased as the alveolar bone height decreased and the orthodontic force increased.Meanwhile,the displacement at each observation point and the crown-root displacement difference increased,and the tendency for inclination movement of the teeth aggravated.When the alveolar bone height was reduced to 2/3,the orthodontic force under lingual and distal movement increased to 150 g and that under intrusion movement increased to 100 g.The periodontal equivalent force increased to the maximum value,and the tendency of tooth inclination movement was most significant.Conclusions A reduction in the alveolar bone height aggravates the stress concentration at the top of the alveolar ridge and the tendency for inclination movement of the teeth.For orthodontic patients with an inferior periodontal condition,the orthodontic force should be reduced according to the alveolar bone height to ensure a safe and effective orthodontic treatment.

Objective To investigate the biomechanical characteristics of orthodontic tooth movement at different alveolar bone heights and provide a theoretical reference for orthodontic clinical treatment.Methods Four groups of mandibular dentition finite element models were established:the normal alveolar bone height,and 1/3,1/2,and 2/3 reductions in height.The lingual,distal,and intrusion movements of the mandibular central incisor were simulated under different loads.The distribution and variations in periodontal stress and tooth displacement were analyzed.Results Under three movements,the degree of stress concentration in the cervical area of the tooth and the periodontal equivalent force increased as the alveolar bone height decreased and the orthodontic force increased.Meanwhile,the displacement at each observation point and the crown-root displacement difference increased,and the tendency for inclination movement of the teeth aggravated.When the alveolar bone height was reduced to 2/3,the orthodontic force under lingual and distal movement increased to 150 g and that under intrusion movement increased to 100 g.The periodontal equivalent force increased to the maximum value,and the tendency of tooth inclination movement was most significant.Conclusions A reduction in the alveolar bone height aggravates the stress concentration at the top of the alveolar ridge and the tendency for inclination movement of the teeth.For orthodontic patients with an inferior periodontal condition,the orthodontic force should be reduced according to the alveolar bone height to ensure a safe and effective orthodontic treatment.