Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

Objective To investigate the role and primary mechanism of a novel fusion gene RELCH-RET in driving the malignant transformation of normal human bronchial epithelial(HBE)cells.Methods Based on retrospective clinical data from 456 non-small cell lung cancer(NSCLC)patients admitted in the Second Affiliated Hospital of Army Medical University from January 2019 to June 2022,a fusion gene,RELCH-RET,was identified as a research target.Three cell models were established:negative control(HBE VC,transfected with empty lentiviral vector),RET control(HBE RET,transfected with lentiviral overexpression vector of Flag-RET),and experimental group(HBE RELCH-RET,transfected with lentiviral overexpression vector of Flag-RELCH-RET).MTS assay and Transwell assay were used to detect cell proliferation and migratory and invasive abilities.In vivo tumorigenicity of the 3 cell models was assessed in 15 female non-obese diabetic/severe combined immunodeficiency(NOD/SCID)mice(SPF grade,4 weeks old,weighing 15.1±0.4 g)via subcutaneous xenograft experiments,with 5 animals in each group.Western blotting was employed to detect the autophosphorylation of RET(Y905)and the phosphorylation of downstream signaling proteins ERK1/2,EGFR(Y845)and STAT3(Y705).Dimerization and multimerization status of RELCH-RET were analyzed by chemical cross-linking(DTME treatment)in combination with Western blotting,with the reversibility being confirmed through de-cross-linking experiments.Results There were 3 cases carrying RELCH-RET fusion gene screened out from the 469 NSCLC patients.Compared with the HBE VC and HBE RET groups,the HBE RELCH-RET group exhibited significantly enhanced cell proliferation(P<0.01),and acquired migratory and invasive abilities(P<0.01),while the control groups did not demonstrate the abilities.In the mouse xenograft tumor model,HBE cells stably expressing RELCH-RET developed significant tumor nodules(P<0.001),whereas the control groups(empty vector and wild-type RET)failed to exhibit detectable tumor growth.Western blotting revealed that RELCH-RET could induce the autophosphorylation of the RET tyrosine residue(Y905)and significantly up-regulate the phosphorylation levels of ERK1/2,EGFR(Y845),and STAT3(Y705)proteins.Chemical cross-linking combined with Western blot analysis demonstrated that RELCH-RET formed a dimer(～170 kDa)in HBE cells,which is reversibly dissociated into monomers upon decross-linking treatment.Conclusion The novel fusion gene RELCH-RET,promotes ligand-independent dimerization/oligomerization,thereby mediating RET autophosphorylation,subsequently activates the downstream typical RET signaling pathway and ultimately drives the malignant transformation of normal HBE cells.

Colorectal cancer is currently one of the most common malignant tumors in the world,and its incidence and mortality rates have gradually increased in recent years.As insidious symptoms characterize early colorectal cancer,most of the patients have already developed into late or advanced stages in the primary survey.For stage Ⅳ metastatic colorectal cancer(mCRC),surgery supplemented with chemotherapy or radiotherapy for mCRC patients has a low 5-year survival rate.With the development of immunology in recent years,PD-1/PD-L1 inhibitors have made breakthroughs in treating malignant tumors.They also have improved the therapeutic efficacy of some mCRC patients,especially those with microsatellite instability-high/mismatch repair deficient.The guidelines recommend this approach.However,patients with microsatellite stable/mismatch repair proficiency,which accounts for more than 90%,are poorly treated with PD-1/PD-L1 inhibitors.Fortunately,there are several clinical studies that reported that some of this type of mCRC can gain some benefit.In this review,we examined the anti-tumor mechanism of PD-1/PD-L1 inhibitors and the latest progress of PD-1/PD-L1 inhibitor's clinical application in patients of mCRC with different genotypes.We discussed the prospect of PD-1/PD-L1 inhibitor combination therapy to provide a reference to the benefit of this type of patients and provide information for optimizing the dosing regimen of PD-1/PD-L1 inhibitors in the treatment of mCRC.

The theory of "liver opens at the eyes" was first seen in Yellow Emperor's Internal Canon of Medicine， which is the ancient people's summary of the connection between the liver and the eyes. The theory of "liver opens at the eyes" suggests the characteristic of "co-damage and co-recover of liver and eyes". It has been found in clinical practice that liver diseases and eye diseases often occur together， and "liver and eyes co-recover" is an ideal choice. The key to achieving "liver and eyes co-recover" is to analyze its pharmacological material basis and mechanism. With the development of modern medicine， more and more evidence indicates that the liver and eyes have complex and close relationships in physiological and pathological aspects. In a pathological state， there is a phenomenon of "liver and eyes co-damage"， and after the intervention of traditional Chinese medicine， "liver and eyes co-recover" occurs. "Liver and eyes co-damage and co-recover" can be explained through the "co-material basis and co-action mechanism". On this basis， the research group tentatively proposed that the liver and eyes had "four common characteristics" （4CCs）， namely "co-damage， co-recover， co-material basis， and co-action mechanism" from the theoretical connotation of traditional Chinese medicine， clinical practice， and molecular biology. Additionally， the group also took the intervention of Prunella vulgaris， traditional Chinese medicine， for removing liver fire and improving eyesight on immune liver injury （ILI） and allergic conjunctivitis （AC） as examples to analyze 4CCs. This project aims to deeply analyze the scientific connotation of the theory of "liver opens at the eyes"， reveal the common characteristics and biological essence of liver and eyes， explore a new research paradigm of "liver and eyes co-recover"， and provide a reference for the study of common problems of multi-organ associated diseases.

Currently, cardiovascular disease has become a major threat to the health of Chinese residents, and prevention and control work is urgent. Self-determination theory is a widely applied theory of behavioral change, extensively used in the field of patient' rehabilitation. This article reviews the content, relevant theoretical models, motivation measurement methods, application status and influencing factors of self-determination theory in the rehabilitation of cardiovascular disease patients, so as to provide a basis for promoting the transition of cardiovascular disease patients to healthy lifestyles and maintaining healthy behavior.

Objective:To analyze the characteristics of lung function in patients with spinal muscular atrophy (SMA) to provide evidence for multidisciplinary management of SMA.Methods:A total of 30 patients with SMA treated in the SMA multidisciplinary clinic of the Children′s Hospital, Zhejiang University School of Medicine from July 2019 to March 2021 were enrolled, including 1 child with type I, 18 patients with type Ⅱ and 11 children with type Ⅲ.There were 17 males and 13 females; the age ranged from 4 years to 21 years and 10 months old.A retrospective study was conducted to analyze the clinical features, spinal imaging findings and lung functions of patients with different clinical types of SMA and explore the factors influencing the lung functions of patients with SMA.Pulmonary function was measured by forced expiratory flow-volume curve.Forced vital capacity (FVC), forced expiratory volume in one second (FEV 1), FEV 1/FVC and peak expiratory flow (PEF) were measured.The results were expressed as the percentage of the measured value to predicted value.The Cobb angle was measured to evaluate scoliosis. Pearson correlation analysis and multiple linear regression analysis were used to evaluate the relationship between lung function and age and Cobb angle in patients with type Ⅱ SMA. Pearson correlation analysis and univariate linear regression analysis were used to evaluate the relationship between Cobb angle and age in patients with type Ⅱ SMA. Results:Pulmonary function in 1 type I patient showed decreased FVC and FEV 1; Among 18 patients with type Ⅱ, 14 cases had abnormal lung function (77.8%): FVC decreased in 12 patients (66.7%), FEV 1 decreased in 10 patients (55.6%), PEF decreased in 12 patients (66.7%). Among 11 patients with type Ⅲ, one had decreased FVC (9.1%). FVC, FEV 1 and PEF of patients with type Ⅱ were significantly lower than those of patients with type Ⅲ [(62.4±31.8)% vs.(90.8±11.0)%, (66.3±33.3)% vs.(97.8±9.9)%, (65.3±30.1)% vs.(98.6±21.1)%, all P<0.01]. Pearson correlation analysis showed that FVC of patients with type Ⅱ SMA was correlated with age and Cobb angle ( r=-0.864, -0.865, all P<0.001), FEV 1 was correlated with age and Cobb angle ( r=-0.878, -0.863, all P<0.001), PEF was correlated with age and Cobb angle ( r=-0.831, -0.783, all P<0.001), and Cobb angle was related to age ( r=0.922, P<0.001). Multiple linear regression analysis indicated that FVC of patients with type Ⅱ SMA was linearly correlated with Cobb angle ( R2=0.748, P<0.001), FEV 1 was linearly correlated with age ( R2=0.770, P<0.001), PEF was linearly related to age ( R2=0.690, P<0.001). Univariate linear regression analysis revealed that Cobb angle of patients with type Ⅱ SMA was linearly related to age ( R2=0.851, P<0.001). Conclusions:FVC, FEV 1 and PEF may decrease in patients with SMA.The degree of lung function damage is different in different types of SMA patients.With the increase of age, Cobb angle increases and FVC, FEV 1 and PEF decrease in patients with type Ⅱ SMA.Understanding the factors influencing the pulmonary function damage in patients with SMA is conductive to carrying out individual multidisciplinary management.

With the boom of China's innovative pharmaceutical industry, licensing-in model has gradually become an important research and development model for innovative pharmaceutical companies. The in-licensed drugs at different stages need different research and development (R&D) strategy in China. The pharmaceutical companies take the responsibility to comprehensively collate the oversea clinical data and conduct a detailed analysis of clinical pharmacology, safety, efficacy and ethnic sensitivity. Clinical R&D strategy should be made based on the results of the above data and analysis. We encourage high-quality drugs which fill unmet clinical needs licensed in, and as early as possible, so as to conduct multi-regional clinical trials (MRCTs). The clinical R&D strategy in China is particularly important for the drug's approval. Guidelines published by the National Medical Products Administration (NMPA) and clinical associations should be followed. Communications about clinical R&D strategy with Center of Drug Evaluation (CDE) are encouraged.
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Antineoplastic Agents/therapeutic use* ; China ; Drug Industry ; Humans ; Lung Neoplasms/drug therapy* ; Pharmaceutical Preparations

The drugs of programmed cell death 1 and its ligand 1 immune checkpoint inhibitors have ushered in a new era of anti-tumor immunotherapy, which has shown outstanding efficacy in some tumors, such as Hodgkin lymphoma, but there is still low response rate in some kinds of tumors. In recent years, bispecific antibodies prepared by cell fusion, recombinant DNA, protein engineering and other technologies can specifically bind two antigens or epitopes at the same time or successively, play a synergistic role in tumor treatment, can effectively inhibit tumor immune escape, and improve the effect of anti-tumor treatment has become a hot spot in tumor research. This paper will summarize the clinical research and development of bispecific antibodies, to provide reference for the industry.
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Antibodies, Bispecific/therapeutic use* ; Antineoplastic Agents ; DNA, Recombinant ; Epitopes ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Ligands ; Lung Neoplasms/drug therapy* ; Neoplasms ; Research

OBJECTIVE：To establish the method for simultaneous determination of 11 active components in Yuhuai tablets ， such as gardoside ，shanzhiside，gardenoside，genipin 1-gentiobioside，geniposide，ziyuglycoside Ⅰ ，ziyuglycoside Ⅱ ，narirutin， naringin，hesperidin and neohesperidin. METHODS ：HPLC-QAMS method was adopted. The determination was performed on Agilent TC-C 18column（250 mm×4.6 mm，5 μm）with mobile phase consisted of acetonitrile （A）-0.1％ phosphoric acid solution （B） （gradient elution ）at the flow rate of 1.0 mL/min. The column temperature was set at 30 ℃. The detection wavelengths were set at 238 nm for gardoside ，shanzhiside，gardenoside，genipin 1-gentiobioside and geniposide ，203 nm for ziyuglycoside Ⅰ and ziyuglycoside Ⅱ，and 283 nm for narirutin ，naringin，hesperidin and neohesperidin. Using geniposide as an internal reference ，the relative correction factors of other 10 components relative to this component were calculated ，and the contents of each component in 10 batches of samples were calculated. The results obtained by HPLC-QAMS method were compared with those obtained by external standard method. RESULTS ：The linear ranges of gardoside ，shanzhiside，gardenoside，genipin 1-gentiobioside，geniposide， ziyuglycoside Ⅰ，ziyuglycoside Ⅱ，narirutin，naringin，hesperidin and neohesperidin were 0.87-43.50，1.99-99.50，4.06-203.00， 7.35-367.50，12.97-648.50，28.98-1 449.00，3.79-189.50，1.57-78.50，18.05-902.50，0.66-33.00 and 14.38-719.00 μg/mL（all r＞0.999 0）. RSDs of precision ，repeatability and stability （24 h）tests were all less than 2％（n＝6）. The average recoveries were 96.90％-100.10％，and RSDs were 0.67％-1.74％（n＝9）. E-mail：289931673@qq.com There was no significant difference in the contents of 10 active components as gardoside between HPLC -QAMS method and external standard method in 10 batches of Yuhuai tablets （P＞0.05）. CONCLUSIONS ：The HPLC-QMAS method established in this study is convenient and accurate. It can be used for the simultaneous determination of gardoside ，shanzhiside，gardenoside，genipin 1-gentiobioside，geniposide，ziyuglycoside Ⅰ，ziyuglycoside Ⅱ，narirutin，naringin，hesperidin and neohesperidin in Yuhuai tablets.