Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Objective:To explore potential biomarkers that can predict the clinical efficacy of PD-1/PD-L1 inhibitors in malig-nancies.Methods:The PubMed,Web of Science,CNKI,Wanfang and VIP databases were searched from the establishment of the database to September 20,2022.After literature screening,data extraction and the risk of bias were evaluated independently by two evaluators,the Meta-analysis was performed using RevMan5.4 and STATA16.0 software.Results:This paper included 18 studies with a total of 4 018 patients.Tumor patients with a high tumor mutational burden(TMB)were found to have higher overall survival(OS)(P=0.003,P=0.01)and progression-free survival(PFS)(P=0.000 2,P=0.04)with PD-1/PD-L1 inhibitors within 1 year and 2 years of follow-up.At different follow-up times,with 1%as the critical value,there was no statistical significance in the level of PD-L1 ex-pression as a biomarker for predicting OS and PFS of PD-1/PD-L1 inhibitors(P>0.05).Conclusion:TMB can be used as a biological indicator to predict the clinical efficacy of PD-1/PD-L1 inhibitors in patients with malignant tumors within 2 years after treatment,but whether its efficacy can last longer remains to be further studied.PD-L1 single test is not currently a biomarker for predicting the bene-fit of PD-1/PD-L1 inhibitors.

Objective:To investigate the expression of stanniocalcin-2 (STC-2) and cellular-mesenchymal epithelial transition factor (C-met) in tumor tissues of cervical cancer patients and their clinical significance.Methods:A total of 110 cervical cancer patients were selected in Foshan First People′s Hospital from January 2014 to December 2018. Patients′ cancer tissue samples and normal tissue samples were collected during modified radical resection to determine and compare the expression levels of STC-2 mRNA and C-met mRNA in the two tissues, and to analyze the correlation between the expression levels of STC-2, C-met and the clinicopathological characteristics of the patients as well as the multivariate analysis of tumor metastasis and recurrence in the patients. The correlation between the expression of STC-2 and C-met and the time of postoperative tumor metastasis and recurrence in cervical cancer patients were analyzed after 24 months of follow-up.Results:The expression levels of C-met mRNA and STC-2 mRNA in cancer tissues were higher than those in adjacent normal tissues: 4.51 ± 1.21 vs. 3.97 ± 1.14, 2.57 ± 0.21 vs. 2.12 ± 0.24, there were statistical differences ( t = 3.41, 14.80, P<0.05). The expression of STC-2 and C-met in cancer tissues had no significant difference with age, pathological type, federation international of gynecology and obstetrics (FIGO) stage and tumor size ( P>0.05), but had significant difference with tumor recurrence or metastasis ( P<0.05). The results of Logistic multivariate analysis showed that vascular emboli, lymph node metastasis, TNM stage, depth of tumor invasion, C-met expression and STC-2 expression were independent risk factors affecting the prognosis of cervical cancer patients ( P<0.05). The expression of STC-2 and C-met were negatively correlated with the time of tumor metastasis in patients with cervical cancer ( r = - 0.663, P<0.001; r = - 0.747, P<0.001). Conclusions:The expression levels of STC-2 and C-met in cancer tissues of cervical cancer patients are higher than those in adjacent normal tissues, and the expression levels of STC-2 and C-met are negatively correlated with the time of metastasis. The expression of C-met, the expression of STC-2, vascular emboli, lymph node metastasis, TNM stage, and the depth of tumor invasion are all independent risk factors affecting the prognosis of cervical cancer patients.

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

[摘 要] 目的：系统评价基于PD-1/PD-L1抑制剂的免疫联合治疗（以下称“免疫联合治疗”）对比舒尼替尼治疗晚期肾细胞癌（RCC）的安全性和有效性。方法：检索PubMed、Embase、Cochrane Library及中国知网（CNKI）数据库，收集国内外公开发表的免疫联合治疗对比舒尼替尼应用于晚期RCC的随机对照试验（RCT），检索时间均为自建库时间至2022年10月。由两名研究者独立评价纳入研究的质量、提取资料并交叉核对，采用StataMP16.0软件进行Meta分析。结果：共纳入6项RCT，Meta分析结果显示，（1）有效性：与舒尼替尼相比，免疫联合治疗显著提高了晚期RCC患者的总生存期[OS，HR=0.74，95% CI （0.67，0.80），P<0.01]和无进展生存期[PFS，HR=0.66，95% CI （0.51，0.81），P<0.01]；（2）安全性：两治疗组均有较高的不良反应（AE）发生率，差异无统计学意义。但免疫联合治疗组发生皮肤及内分泌系统AE显著高于舒尼替尼治疗组，而血液系统相关AE则明显低于舒尼替尼治疗组；（3）以1%为临界点，免疫联合治疗组的RCC患者，无论是PD-L1阳性或阴性的，其OS和PFS均高于舒尼替尼组。结论：免疫联合治疗可显著延长晚期RCC患者的OS和PFS，但不同系统发生AE有差异，且RCC患者PD-L1表达状态（1%为临界点）并不影响免疫联合治疗的获益。

Malocclusion is an oral disease with a high prevalence. The goal of orthodontic treatment is health, aesthetics, function and stability. The transmission straight wire appliance and technique is an innovative orthodontic system with independent intellectual property rights invented by Professor Jiuxiang Lin′s team based on decades of clinical experience, which provides a new solution for the non-surgical correction of skeletal malocclusions, especially class Ⅲ malocclusion, and it is also a good carrier for the implementation of the concept of healthy orthodontics. Due to the lack of guidelines, how to implement standardized application of transmission straight wire technique remains a problem to be solved. This technical specification was formed by combining the guidance from Professor Jiuxiang Lin and joint revision by a number of authoritative experts from the Orthodontic Special Committee, Chinese Stomatological Association, with reference to relevant literatures, and combined with abundant clinical experience of many experts. This specification aims to provide reference to standardize the clinical application of transmission straight wire technique, so as to reduce the risk and complications, and finally to improve the clinical application level of this technique.

Objective:To investigate the clinical efficacy and safety of ixazomib-based therapy in patients with relapsed or refractory multiple myeloma (RRMM) .Methods:A retrospective analysis was performed on the efficacy and adverse reactions of 53 RRMM patients treated with a combined regimen containing ixazomib in the Hematology Department of Beijing Jishuitan Hospital from July 8, 2018 to November 30, 2020. Among them, 6 patients received ID regimen (ixazomib + dexamethasone) , 30 patients received ID regimen + immunomodulator, and 17 patients received ID regimen + other chemotherapy drugs.Results:Fifty-three patients with RRMM received ixazomib-based therapy. The median previous treatment line was 3, the median treatment course was 6 (2-30) , and the median follow-up time was 21 months (2-32 months) . The overall response rate (ORR) was 54.7% (29/53) after 2 courses of treatment. Among them, 26.4% (14/53) had very good partial response (VGPR) and 28.3% (15/53) had partial response (PR) . The ORR of the ID regimen group, ID regimen + immunomodulator group and ID regimen + other chemotherapy group were 83.3% (5/6) , 56.7% (17/30) and 41.2% (7/17) respectively, with no statistically significant difference among the three groups ( P=0.208) . The median time to progression (TTP) of 53 patients was 8 months (1-24 months) . The most frequent adverse events of ixazomib treatment were gastrointestinal reactions such as nausea, vomit and diarrhea, with an incidence of 37.7% (20/53) , and the incidence of grade 3-4 was 5.7% (3/53) . The most common hematological adverse events were thrombocytopenia (15.1%, 8/53) , neutropenia (11.3%, 6/53) and anemia (9.4%, 5/53) . Grade 1-2 peripheral neurotoxicity occurred in only 7.5% (4/53) of patients. Conclusion:Ixazomib has good efficacy and safety for the patients with RRMM in the real world.

Objective To analyze the epidemiological characteristics and seasonal distribution of hand, foot and mouth disease (HFMD) in a suburban town in Shanghai from 2012 to 2018, and to provide a scientific basis for formulating effective prevention and control strategies. Methods The incidence data of a suburban town in Shanghai from 2012 to 2018 was collected through the Chinese disease prevention and control information system and analyzed by descriptive epidemiological methods. Results From 2012 to 2018, a total of 538 cases of hand, foot and mouth disease were reported in the suburban town in Shanghai, with an average annual incidence of 186.27/100,000. The difference in incidence between each year was statistically significant (χ²=107.95, P<0.05). The age of onset was mainly children under 5 years old. Peak incidence was from May to September. The main occupation was scattered children. HFMD outbreaks mainly occurred in nurseries and schools, accounting for 60.53% of the total number of outbreaks. Conclusion From 2012 to 2018, the incidence of HFMD in a suburban town in Shanghai had a certain seasonality. It is recommended to implement preventive measures against HFMD for key populations and key places before the high incidence period to reduce the occurrence of severe cases and epidemic situations.

Objective:To explore the effects of problem-solving therapy on breastfeeding self-efficacy and psychological status among primiparas, to provide basis for improving the breastfeeding of primipara.Methods:A total of 102 primiparas were divided into experimental group and control group by random number table method, each group contained 51 cases. Finally, 47 cases in the experimental group and 49 cases in the control group completed the study. The control group received routine nursing, while primiparas in the experimental group carried out problem-solving therapy. Before and after 6-week intervention, the effects was assessed by Breastfeeding Self-Efficacy Scale (BSES), Edinburgh Postnatal Depression Scale (EPDS) and General Well-being Schedule (GWB), respectively.Results:After intervention, the scores of primapara feedig cognition, feeding feeling, feeding skills and BSES total scores were (21.13±2.97) points, (65.47±6.63) points, (31.94±2.59) points, (118.53±8.47) points in the experimental group, significantly higher than (19.43±3.28) points, (61.76±5.20) points, (30.53±2.01) points, (111.71±6.11) points in the control group ( t values were 2.658-4.507, P<0.01); the scores of EPDS were (6.04±1.49) points in the experimental group, significantly lower than (6.92±2.08) points in the control group; the scores of life satisfaction and interest, depression and pleasure, energy, relaxation and tension in General Well-Being (GWB) and total scores were (7.51±1.71) points, (20.19±2.47) points, (21.68±2.32) points, (17.06±2.74) points, (90.45±4.96) points in the experimental group, significanlty higher than (6.41±1.82) points, (18.71±2.98) points, (20.57±1.87) points, (15.78±1.79) points, (84.61±5.26) points in the control group, the difference was statistically significant ( t values were 2.380-5.587, P<0.05 or 0.01). Conclusion:Problem-solving therapy can improve breastfeeding self-efficacy and alleviate postnatal depression as well as enhance subjective well-being of primipara women.

Objective To analyze the disease constitution,accuracy of clinical and pathological diagnoses of skin biopsy samples in Peking Union Medical College Hospital.Methods A total of 29987 patients subjected to skin biopsy were collected from Department of Dermatology,Peking Union Medical College Hospital from June 2010 to November 2018,and clinical and histopathological diagnoses of these skin biopsy samples were analyzed retrospectively.Results According to the results of histopathological diagnosis,confirmed diagnoses of these patients could be classified into 33 categories and 242 kinds.Common disease categories included epidermal tumors (2931 cases,9.77％),connective tissue diseases (2809 cases,9.37％),melanocytic tumors (2078 cases,6.93％),erythematous scaly pustular dermatoses (1376 cases,4.59％),lichenoid dermatoses (1291cases,4.31％),allergic or eczematous skin diseases (1282 cases,4.28％)and infectious skin diseases (1156 cases,3.86％).Common skin diseases included scleroderma (1887 cases,6.29％),pigmented nevus (1755 cases,5.85％),seborrheic keratosis (1136 cases,3.79％),eczema (1089 cases,3.63％),psoriasis (881 cases,2.94％),lichen planus (867 cases,2.89％),lupus erythematosus (638 cases,2.13％),pemphigus (549 cases,1.83％),and basal cell carcinoma (501 cases,1.67％).Poor consistency was observed between clinical diagnosis and histopathological diagnosis of lichen planus,bullous pemphigoid,granuloma annulare and hypereosinophilic dermatitis.Conclusions Common disease categories of the skin biopsy samples in Peking Union Medical College Hospital were epidermal tumors,connective tissue diseases,melanocytic tumors,erythematous scaly pustular dermatoses,lichenoid dermatoses,and allergic or eczematous skin diseases.Poor consistency was observed between clinical and pathological diagnosis in some skin diseases,and understanding of these diseases should be improved.