The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Objective To evaluate the efficacy of intravascular intervention in the treatment of multiple intracranial aneurysms(MIAs).Methods The clinical data of MIAs patients,who were treated with intravascular intervention from December 2013 to December 2021 in Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,were collected and were analyzed by using statistical methods.Results A total of 105 MIAs patients were enrolled in this study,and among them 77 patients(73.3％)were complicated by subarachnoid haemorrhage.Intravascular intervention was performed for 192 of the 240(80.0％)intracranial aneurysms(I As),including 142 IAs receiving one-stage treatment and 50 IAs receiving multi-stage treatment.In 66 patients,all the IAs were treated.Simple spring coil embolization was performed for 84 IAs and stent-assisted spring coil embolization was carried out for 108 IAs.During the follow-up period,11 patients developed recurrent IAs,which received treatment again.There was no obvious statistical difference in the treatment results between the patients receiving one-stage treatment and the patients receiving multi-stage treatment(P＞0.05).There was also no obvious statistical difference in the follow-up findings and prognosis results between the patients receiving one-stage treatment and the patients receiving multi-stage treatment(P＞0.05).Conclusion For the treatment of MIAs,the clinical efficacy of one-stage intravascular treatment and multi-stage intravascular treatment is roughly the same.However,one-stage treatment should be adopted as far as possible when the technical conditions permit.

Objective To investigate the regulatory effect of circular RNA ASAP1(circASAP1)targeting microRNA-4500(miR-4500)on the proliferation and apoptosis of osteosarcoma cells.Methods Human osteosarcoma cells(Saos-2)were selected as the experimental subjects and cul-tured in DMEM medium containing 10％fetal bovine serum while maintaining 5％CO2.The expres-sions of circASAP1 and miR-4500 in osteosarcoma tissues were detected using RT-qPCR.Saos-2 cells were transfected with si-NC(40 nmol/L),si-circASAP1(40 nmol/L),pcDNA(0.4 μg),pcDNA-circASAP1(0.4 μg),miR-NC(40 nmol/L),miR-4500 mimics(40 nmol/L),si-circASAP1+anti-miR-NC(40 nmol/L),and si-circASAP1+anti-miR-4500(40 nmol/L),respectively.Cell proliferation and apoptosis were assessed using CCK-8,colony formation assays,and flow cytometry.The interaction between circASAP1 and miR-4500 was analyzed using a dual-luciferase reporter assay.Results Compared with adjacent non-tumor tissues,the expression of circASAP1 was significantly upregulated,while that of miR-4500 was significantly downregulated in osteosarcoma tissues(P＜0.001).Compared with the si-NC group,the si-circASAP1 group exhibited significantly decreased circASAP1 expression,optical density(OD)values,and the number of cell colonies(P＜0.001).Compared with the si-NC group,the si-circASAP1 group showed significantly upregulated levels of cleaved-caspase3 protein,cleaved-caspase9 protein,and the apoptosis rate(P＜0.001).StarBase search revealed specific binding sequences between miR-4500 and circASAP1.Co-transfection of miR-4500 mimics and WT-circASAP1 significantly reduced the relative luciferase activity of the cells[(0.34±0.03)versus(0.95±0.06),t=27.280,P＜0.001].The expression of miR-4500 in the pcDNA-circASAP1 group was significantly lower than that in the pcDNA group,whereas the ex-pression of miR-4500 in the si-circASAP1 group was significantly higher than that in the si-NC group(P＜0.001).Compared with the miR-NC group,the miR-4500 group exhibited significantly in-creased miR-4500 expression,cleaved-caspase3 protein levels,cleaved-caspase9 protein levels,and the apoptosis rate,while the OD values and the number of colonies significantly decreased(P＜0.001).Compared with the si-circASAP1+anti-miR-NC group,the si-circASAP1+anti-miR-4500 group showed significantly decreased miR-4500 expression,cleaved-caspase3 protein levels,cleaved-caspase9 protein levels,and the apoptosis rate,while the OD values and the number of col-onies significantly increased(P＜0.001).Conclusion The expression of circASAP1 is increased,while that of miR-4500 is decreased in osteosarcoma tissues.Moreover,circASAP1 promotes the proliferation and inhibits the apoptosis of osteosarcoma cells by targeting miR-4500.

Objective:To evaluate the efficacy and safety of 308-nm excimer lamp and 308-nm excimer laser in the treatment of pediatric vitiligo.Methods:Clinical data were collected from children with stable vitiligo who received targeted phototherapy at the Department of Dermatology of Xijing Hospital from 2010 to 2015, and retrospectively analyzed. The patients were treated with either 308-nm excimer laser or 308-nm excimer lamp, and all were given topical drugs. The treatment lasted for at least 3 months, and follow-up for at least 6 months. The severity of vitiligo was assessed using the Vitiligo Area and Severity Index (VASI) score. The efficacy was evaluated after 3 months of treatment, and at least a 50% reduction in the VASI score (VASI50) was defined as "effectiveness". A logistic regression model was constructed using treatment efficacy as the dependent variable to screen factors related to the treatment outcome. The Wilcoxon signed-rank test was used to compare skewed data before and after treatment. Adverse reactions during treatment were recorded to evaluate the safety of targeted phototherapy.Results:A total of 194 children with stable vitiligo were included, comprising 103 males (53.1%) and 91 females (46.9%), with the age being 6 to 14 (10.2 ± 2.3) years. Among them, 138 (71.1%) received 308-nm excimer laser therapy, while 56 (28.9%) received 308-nm excimer lamp therapy. The VASI score ( M [ Q1, Q3]) was 0.12 (0.05, 0.40) at the baseline, significantly decreased to 0.06 (0.02, 0.19) after 3 months of treatment ( Z = 12.02, P < 0.001). After 3 months of treatment, 52 patients achieved VASI50, and 30 achieved VASI75, resulting in an overall response rate of 42.3% (82/194). Specifically, in the 308-nm excimer laser group, 38 patients achieved VASI50 and 26 achieved VASI75, with a response rate of 46.4% (64/138) ; in the 308-nm excimer lamp group, 14 patients achieved VASI50 and 4 achieved VASI75, yielding a response rate of 32.1% (18/56). Univariate logistic regression analysis indicated that lesions located on the head and neck or the trunk were more prone to repigmentation compared with those on the limbs ( OR = 3.56, 95% CI: 1.15 - 11.02, P = 0.027; OR = 6.58, 95% CI: 1.81 - 23.96, P = 0.004, respectively) ; additionally, facial lesions around the eyes were more prone to repigmentation compared with lesions on other facial areas ( OR = 4.58, 95% CI: 1.10 - 19.11, P = 0.037), and hair involvement in vitiligo lesions on the head and neck made repigmentation less likely to occur compared with lesions without hair involvement ( OR = 0.31, 95% CI: 0.13 - 0.75, P = 0.010). Multivariate logistic regression analysis revealed that the periorbital region was the most favorable site for repigmentation among facial areas ( OR = 5.37, 95% CI: 1.18 - 24.34, P = 0.029), and hair involvement in vitiligo lesions on the head and neck was an independent risk factor for phototherapy-induced repigmentation ( OR = 0.28, 95% CI: 0.08 - 0.96, P = 0.042). Among the 194 patients treated with targeted phototherapy for 3 months, 33 experienced short-term treatment-related adverse reactions, including erythema, blisters, desquamation, itching, and pain; most adverse reactions were mild, and no severe adverse reactions were observed. Conclusion:Targeted phototherapy using 308-nm excimer laser or 308-nm excimer lamp was safe and effective for the treatment of pediatric vitiligo.

Objective A simple,specific and rapid LC-MS/MS method was established to determine flumatinib and its two major metabolites in human plasma for clinical therapeutic drug monitoring.Methods The determination was performed on an ACQUITY UPLC HSS T3 column(2.1 mm×50 mm,1.8 μm)with mobile phases consisting of acetonitrile and 10 mmol·L-1 ammonium formate(containing 0.1%formic acid)with gradient elution at the flow rate of 0.5 mL·min-1.The elution time was 6 min.The temperature of the column was 38℃.The ion source was electrospray ion source and the scanning mode was multiple reaction monitoring scanning in positive ion mode.Results The mass concentrations of flumatinib and its metabolites(flumatinib M1 and flumatinib M3)have a good linear relationship within the concentration range investigated.The precision and stability of the method are good.The precision is less than 15%,and the relative deviation is within±15%.The extraction recoveries of flumatinib and its metabolites approach nearly 100%.Conclusion The method is simple and sensitive,and can accurately determine the plasma concentration of flumatinib and its metabolites,providing a basis for clinical rational drug use.

OBJECTIVE To expl ore the clinical significance of folic acid metabolic gene detection in methotrexate （MTX） treatment of acute myeloid leukemia （AML）. METHODS Therapeutic drug monitoring （TDM）pharmacists participated in the treatment process of an AML patient who had neurotoxic side effects such as dizziness ，headache，and vomiting after intrathecal injection of MTX. According to the results of the test of the folic acid metabolic gene MTHFR C677T（rs1801133）（mutant homozygous）and the results of MTX blood concentration monitoring （＜0.05 μmol/L），combined with clinical manifestations ，it was recommended to stop MTX ，give intravenous drip of calcium folinate for rescue ，and consider using azacytidine for follow-up treatment. RESULTS The doctor took the advice of TDM pharmacist ，and the above symptoms were significantly relieved after the patient rescued for 2 times and successfully discharged from the hospital. CONCLUSIONS For AML patients who meet the indications and receive intrathecal injection of MTX ，drug metabolism genetics testing and MTX drug concentration monitoring can be performed before medication ，which helps doctors and pharmacists evaluate the feasibility of drug treatment options and reduce medical risks.

In the original publication the bands in Fig. 1J and Fig. 2B were not visible. The correct versions of Fig. 1J and Fig. 2B are provided in this correction.

Background: Endoscopic submucosal dissection has become the preferred treatment for early gastric cancer without lymph node metastasis (LNM). The risk of LNM is different among different pathological types of early gastric cancer. Aims: To investigate the risk factors of LNM in patients with early gastric cancer. Methods: The clinicopathological features of 1 093 early gastric cancer patients underwent radical gastrectomy and diagnosed by pathology from January 2005 to December 2019 at Nanjing Drum Tower Hospital and Nanjing Gaochun People's Hospital were retrospectively analyzed. Risk factors of LNM in patients with early gastric cancer were analyzed by univariate analysis and logistic regression model analysis. Results: A total of 1 093 patients with early gastric cancer were enrolled, and positive LNM was found in 154 patients (14.1%). Univariate analysis showed that gender, age, tumor size, tumor location, gross classification, depth of tumor invasion, vascular and nerve invasion, differentiation type, ulcers were related with LNM (P<0.05). Multivariate analysis showed that age (OR=1.654, 95% CI: 1.102-2.480, P=0.015), tumor location (OR=1.617, 95% CI: 1.227-2.131, P=0.001), differentiation type (OR=1.664, 95% CI: 1.205-2.298, P=0.002), depth of invasion (OR=1.569, 95% CI: 1.212-2.030, P=0.001), vascular invasion (OR=10.514, 95% CI: 6.353-17.401, P=0.000) were the independent risk factors of LNM in early gastric cancer. Conclusions: Age, tumor location, differentiation type, depth of invasion, and vascular invasion are the independent risk factors of LNM in early gastric cancer, especially vascular invasion. For patients with vascular invasion, if there are no contraindications, surgical intervention is recommended.

Objective? To investigate the status of caregiver preparedness and adult attachment among the spouse of young and middle-aged stroke patients,and to analyze the correlation between them. Methods? From January 2017 to May 2018,110 spouses of stroke patients who were treated in Affiliated Hangzhou First People＇s Hospital, Zhejiang University School of Medicine were selected as subjects by convenience sampling. The General Information Questionnaire,Care Preparedness Scale (CPS),and Experience in Close Relationship Scale (ECR) were used in the survey. Totally 110 questionnaires were distributed, and 102 valid ones were retrieved, yielding an effective recovery rate of 92.73%. Results? The total CPS score of 102 young and middle-aged stroke patients was (12.87±5.39). The scores of attachment anxiety and attachment avoidance in ECR were (57.96 ±11.69) and (48.06 ±12.10). There were statistically significant differences in the scores of preparedness of caregivers among spouse caregivers of different ages, self reported health status and nursing experience (P＜ 0.05). Attachment anxiety dimension was negatively correlated with caregiver preparedness score (r=-0.318,P＜0.01), and attachment avoidance dimension was negatively correlated with caregiver preparedness score (r=-0.233,P＜ 0.01). Conclusions? The preparedness status of the spouses caregivers of young and middle-aged stroke patients are at a low level. Medical workers can improve their care preparedness by giving them home care knowledge guidance,reducing their attachment avoidance and attachment anxiety so as to improve their preparedness.

Objective? To analyze the root causes of fall in elderly patients, explore the corresponding countermeasures and combine the balance function and knee joint strengthening training to reduce the incidence of fall in elderly patients. Methods? First, the cause of fall of the patients in the department of rehabilitation from November 2014 to October 2016 were analyzed with the method of root cause analysis and retrospective analysis, and targeted corrective measures were formulated. The elderly patients fell between the time period from November of 2016 to October of 2017 and November of 2017 to October of 2018 were enrolled into the control group and observation group by convenience sampling. Corrective measures were formulated based on root cause analysis and action (RCA2) to prevent falls in the control group, on the basis of that balance function training combined with strengthening training of knee joint control were adopted to prevent fall in the observation group. The two groups were compared in terms of the differences in the incidence of fall, five times of sitting and standing test(FTSST), 10 meters maximum walking speed (10MWS), Berg Balance Scale(BBS)and Tinetti Gait Analysis (TGA). The incidence of fall in the department before the implementation of corrective measures based on RCA2(November 2014 to October 2016) and the time period of November 2016 to October 2018 which is after the implementation of RCA2 based corrective measures were compared. Results? After implementing the corrective measures, the fall rate of the elderly patients reduced from 2.0% to 0.9% with statistical difference (χ2=4.343, P=0.037). There was statistical difference (χ2=3.899, P=0.048) in terms of the incidence of fall between the observation group (4.24%) and the control group (0.64%). Before intervention, the two groups had no statistical difference in the FTSST, 10MWS, BBS and TGA(P＞0.05). In the control group, there was no statistical difference before and after intervention (P＞ 0.05); in the observation group, there was statistical difference before and after intervention (P＜0.05). After intervention, the observation group was better than the control group in the FTSST, 10MWS, BBS and TGA with statistical difference (P＜0.05). Conclusions? The comprehensive use of root cause analysis and intensive training of knee joint control and balance function training to manage elderly patients scientifically can effectively reduce the incidence of falls.