Objective This study aims to provide craniofacial features and incisor position prediction models among esthetics population after orthodontic treatment.Methods A total of 338 patients with esthetic profiles were se-lected from 1 055 post-orthodontic adults based on inclusion and exclusion criteria and scored by five dental students.Mean values of cephalometric measurement were demonstrated with gender and sagittal skeletal pattern(ANB)differ-ences assessed by generalized estimating equation.Correlations among age,skeletal,and soft tissue variables in differ-ent genders were determined.Multivariate analysis was used to assess the influence of skeletal and soft tissue variables on orthodontic incisor position.Results Within the esthetic cohort after orthodontic treatment,gender differences ex-isted in cranial and mandibular length,mandibular rotation,protrusion of pogonion,inclination of maxillary incisors,upper lip thickness,lower 1/3 face height,and nose protrusion.However,in class Ⅰ malocclusion,the development of the chin showed no significance,whereas the protrusion of the lower lip significantly differed between genders,with less protrusion in males.In males,the protrusion of lip and chin varied among groups,with thinner basic upper lip thick-ness of class Ⅱ than class Ⅰ and greater lower lip height of class Ⅲ than class Ⅰ.In females,the protrusion and height of the upper lip and chin varied in groups,with thicker basic upper lip thickness of class Ⅲ than class Ⅰ.Upper lip thickness,female basic upper lip thickness,and female lower lip height were correlated with age.The protrusion of the upper lip was mainly correlated with posterior cranial base,mandibular body length,ANB in male and SNA,ANB,sag-ittal maxillary length,mandibular rotation,and protrusion of pogonion in female.The protrusion of the lower lip in males was mainly correlated with ramus height,mandibular rotation,protrusion of pogonion in male and ANB,mandib-ular rotation,and protrusion of pogonion in females.After employing skeletal variables to fit dental parameters,optimal results were achieved in male IMPA(adjusted R2=0.712)and female G Vert-U1(adjusted R2=0.795).After employing skeletal and soft tissue variables simultaneously,optimal results were achieved in male and female G Vert-U1,which was mainly influenced by the protrusion of the chin and nasal base in males(adjusted R2=0.836)and the protrusion of the nasal base as well as ANB in females(adjusted R2=0.842).Conclusion This study demonstrated the craniofacial features of esthetics population after orthodontic treatment and revealed the correlation of gender,age,skeleton,and soft tissues to provide reliable prediction models for aesthetic orthodontic incisor position.

OBJECTIVE To discuss medical insurance access and pricing methods for multi-indication drugs. METHODS The access situation of multi-indication drugs in China’s medical insurance negotiation over the years was sorted out. Referring to the economic theory of value-based pricing and the relevant experience of other countries， five applicable pricing methods of 3 categories for multi-indication drug in China were summarized. Taking ceftazidime-avibactam（CAZ-AVI） as an example， cost- utility analyses were performed for different indications， and appropriate pricing methods were applied. RESULTS & CONCLUSIONS All multi-indication drugs in China adopted a single pricing method. The pricing methods that could be explored include product-based pricing， such as single pricing based on the lower-value indication or mixed/weighted single pricing； indication-based pricing， such as developing a new agreement for single pricing under different discounts and listing with different brands and pricing of the same medicine for different indications； and compensation for access restrictions. Each method has its advantages and limitations. The case of CAZ-AVI showed that it is necessary to estimate the value of each indication for multi- indication drugs， and comprehensively consider appropriate access conditions and pricing methods based on value. Although single pricing is simple to operate， it is different to reflect the value entirely. The indication-based pricing and compensation for access restrictions all depend on the information collection system and the cooperation of multiple departments. China is supposed to carry out the value-based pricing of multi-indication drugs and constantly explore reasonable access methods to improve overall social welfare.

Objective: To provide reliable prediction models based on dentoskeletal and soft tissue variables for customizing maxillary incisor positions and to optimize digitalized orthodontic treatment planning. Methods: This study included 244 Chinese women (age, 18–40 years old) with esthetic profiles after orthodontic treatment with fixed appliances (133 in group I: 1° ≤ The angle between the nasion [N]-A point [A] plane and the N-B point [B] plane [ANB] ≤ 4°; 111 in group II: 4° < ANB ≤ 7°). Dental, skeletal, and soft tissue measurements were performed on lateral cephalograms of the participants. Correlation and multiple linear regression analyses were used to determine the influence of dentoskeletal and soft tissue variables on maxillary incisor position. Results: The ideal anteroposterior position of the maxillary incisor varied between sagittal skeletal patterns. The position of the maxillary incisor correlated with the sagittal discrepancy between the maxilla and the mandible (ANB), protrusion of the midface, nasal tip projection, development of the chin, and inclination of both the maxillary and mandibular incisors. Distance from the maxillary central incisor to nasion-pogonion plane predicted using multiple linear regression analysis was accurate and could be a practical measurement in orthodontic treatment planning. Conclusions Instead of using an average value or norm, orthodontists should customize a patient’s ideal maxillary incisor position using dentoskeletal and soft tissue evaluations.

OBJECTIVE：To evaluate the economy performance of dexamethasone （DXM）combined with rituximab （RTX） for the first-line treatment of chronic primary immune thrombocytopenia （ITP）in adults. METHODS ：From the perspective of China ’s medical and health system ，Markov model for eight states was constructed with a period of 4 weeks and a time limit of 20 years， using DXM regimen as control. The cost-utility of DXM+RTX regimen for the treatment of chronic ITP in adults were evaluated. The parameters of clinical efficacy and utility value were derived from own published literature ；cost parameters were from the MENET website and the official websites of local health committees and medical insurance bureaus ；one-way sensitivity analysis ， probability sensitivity analysis and scenario analysis were performed to observe the uncertainty of model and data source. RESULTS：The average cost of DXM+RTX regimen was 51 064 dollars and that of DXM regimen was 50 455 dollars. Compared with DXM regimen ，DXM+RTX regimen yielded an additional 0.14 QALYs for each patient ；the incremental cost-effectiveness ratio（ICER）was 4 356 dollars/QALY，and was lower than the willingness-to-pay threshold of China ’s per capita gross domestic product（GDP）in 2020. In the one-way sensitivity analysis ，the cost of drugs was the main driver in the model. Probability sensitivity analysis demonstrated that DXM+RTX regimen had 57.5％-61.0％ probability of being cost-effective at a willingness- to-pay threshold of 1-3 times per capita GDP in 2020. The results of scenario analysis showed that DXM+RTX regimen would have obvious long-term benefits ，and the utility value had little impact on the conclusion. CONCLUSIONS ：DXM + RTX is more economical than DXM in the treatment of chronic ITP in adults ，but the results have the uncertainty.

Relapse or metastatic esophageal squamous cell carcinoma (ESCC) has poor prognosis and limited treatment options. Chemotherapy based on platinum agents combined with fluorouracil or taxanes is the standard first-line treatment for it. Molecular-targeting agents, mainly epidermal growth factor receptor inhibitors including cetuximab, panitumumab, nimotuzumab and gefitinib, have failed to improve the survival of patients with advanced ESCC. Anlotinib, one of the small molecule multi-target tyrosine kinase inhibitors, can prolong the median progression free survival in patients treated with above the second line. Compared with chemotherapy, immune checkpoint inhibitors (including nivolumab, pembrolizumab and camrelizumab) significant improve overall survival times in patients with ESCC who fail to the first line chemotherapy, and can be selected as the standard second line treatment. Immunotherapy combined with chemotherapy or anti-angiogenic therapy for first-line treatment of advanced ESCC is also being studied.

OBJECTIVE：To provide reference for impro ving the quality of programmed cell death protein 1 （PD-1）/ programmed cell death 1 ligand（PD-L1）inhibitors in the treatment of non-small cell lung cancer related pharmacoeconomic studies in China. METHODS ：Retrieved from Embase ，PubMed，Medline，Cochrane Library ，CNKI，Wanfang database ，VIP and other Chinese and English database ，cost-utility studies about PD- 1/PD-L1 inhibitors in the treatment of non-small cell lung cancer published during Jan. 2016-Jan. 2021 were collected. The data of the included studies were extracted. After the quality of the included studies was evaluated by using the Consolidated Health Economic Evaluation Reporting Standards list ，the relevant data were summarized and compared from the aspects of model framework ，model parameters and uncertainty analysis. RESULTS & CONCLUSIONS：A total of 17 studies were finally included ，the overall quality of them was high but the differences in methodology were great. Markov model or partition survival model based on three states was adopted for 16 studies. The time horizon ranged from 5 years to lifetime ；the cycle length ranged from 1 week to 6 weeks. A total of 8 studies used the standard parameter distribution method for parameter fitting ，and 7 studies additionally adopted other parameters estimation methods as KM curves or spline models. Eleven studies performed the validation of model extrapolation. All studies considered the direct medical costs and reported the incremental cost-effectiveness ratio using quality-adjusted life years as the health outcome. Sixteen studies conducted the deterministic sensitivity analysis and probabilistic sensitivity analysis to improve the stability of the model. It is suggested that studies should keep the integrity of the report ； format，choose the appropriate positive comparators ，selectthe health economic model and construct reasonable assumptions according to the available data format ， use Cholesky decomposition to explore the uncertainty of the parameter fitting ， perform the validation of extrapolation combined with external data and use the appropriate indirect comparison in the absence of the head-to-head clinical trials to improve the quality of related pharmacoeconomic studies in China.

Objective:To investigate the effects of different treatment modes on the survival of patients with non-small cell lung cancer (NSCLC) brain metastases, and to evaluate the clinical values of diagnosis-specific graded prognostic assessment (DS-GPA) model and graded prognostic assessment model for lung cancer using molecular markers (Lung-molGPA).Methods:The clinical data of 195 NSCLC patients with brain metastases treated in the Cancer Hospital of Shantou University Medical College from January 2011 to December 2015 were retrospectively analyzed, including 112 patients without brain metastasis (metachronous brain metastases) at the first diagnosis, and 83 patients with brain metastases at the first diagnosis (simultaneous brain metastases). The treatment modalities of brain metastases included single local cranial radiation, chemotherapy, target therapy and combined cranial radiation with chemotherapy or target therapy, chemotherapy plus target therapy, et al. Kaplan-Meier method was used for survival analysis, Cox regression method was used for univariate and multivariate survival analyses, and DS-GPA and Lung-molGPA models were used for survival analysis.Results:The median time to brain metastases in all patients was 14.1 months (95% CI 12.2-16.0 months). The median progression-free survival (PFS BM) time of all patients was 4.3 months (95% CI 3.4-5.2 months), and the median overall survival (OS BM) time of brain metastases was 6.7 months (95% CI 4.6-8.8 months). There was no difference in PFS BM and OS BM between patients with synchronous and metachronous brain metastases ( P = 0.446, P = 0.080). Receiving anti-tumor therapy, especially combining targeted therapy could improve median OS BM. Low Karnofsky score ( RR = 1.698, 95% CI 1.238-2.329, P = 0.001) and bone metastasis ( RR = 1.505, 95%CI 1.089-2.081, P = 0.013) were independent risk factors for the OS BM of NSCLC patients with brain metastases, and chemotherapy ( RR = 0.460, 95% CI 0.289-0.731, P = 0.001) and brain radiotherapy ( RR = 0.541, 95% CI 0.391-0.749, P < 0.01) were independent protective factors for the OS BM of NSCLC patients with brain metastases. The OS BM difference between patients grouped by DS-GPA and Lung-molGPA models was statistically significant (median OS BM time of patients with DS-GPA model 0.0-1.0, 1.5-2.0 and 2.5-3.0 points were 4.2, 9.4 and 10.9 months, respectively, P = 0.015; median OS BM time of patients with Lung-molGPA model 0.0-1.0, 1.5-2.0 and 2.5-3.0 points were 4.1, 8.7 and 13.0 months, respectively, P < 0.01). Conclusions:The prognosis of NSCLC patients with brain metastases is poor, and anti-tumor therapy can prolong their survival. High Karnofsky score, without bone metastasis, receiving chemotherapy or brain radiotherapy are independent good prognostic factors for NSCLC patients with brain metastases. Both DS-GPA and Lung-molGPA models can predict the survival of NSCLC patients with brain metastases.

PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. MATERIALS AND METHODS: Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP-14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. RESULTS: Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. CONCLUSION: R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.
Asian Continental Ancestry Group ; B-Lymphocytes ; Cyclophosphamide ; Disease-Free Survival ; Doxorubicin ; Follow-Up Studies ; Humans ; Lymphoma, B-Cell ; Prednisone ; Prognosis ; Rituximab ; Vincristine

Objective: To investigate the health of gypsum miners in Hubei province and analyze the health effects of occupational disease hazards exposure on gypsum miners. Methods: In April 2017, occupational disease hazard factors were tested on the site of a gypsum mine, and 500 workers were selected by random sampling to conduct questionnaires, relevant data such as occupational health examination was collected, and descriptive statistical analysis was performed. Results: The main occupational hazards of gypsum miners were gypsum dust and noise. The time-weighted average concentration of 8 h in the workplace was 4.32 to 9.34 mg/m³, and the post pass rate was 69.2% (9/13) ; Respiratory dust 0.13-5.15 mg/m³, post pass rate 75.0% (3/4). Gypsum miners had finger dysfunction and muscle numbness, joint pain (29.2%, 88/301) and chest pain and breathing difficulties (17.6%, 53/301). Followed by tinnitus, auricle pus, running water (4.7%, 14/301), abnormal muscle tension (2.7%, 8/301). The exposure of occupational disease hazards was associated with respiratory, auditory and neurological symptoms of gypsum miners. Conclusion The long-term exposure of gypsum workers to gypsum dust, noise and other harmful factors may result in obvious symptoms of respiratory system and other health damage.

Desmoplastic small round cell tumor (DSRCT) is a rare and high malignant soft tissue tumor with very poor prognosis.It usually occurs in the abdominopelvic cavity of adolescents and young males.DSRCT is prone to occur distant metastasis,mainly in the liver and lung.The histopathological manifestation is featured with nests of small round blue cells separated by desmoplastic stroma.DSRCT can co-express epithelial,neural and mesenchymal markers.The molecular characteristic of DSRCT is the production of EWSWT1 fusion protein via the translocation of chromosome t (11;22) (p13;q12).Treatments of DSRCT include radical resection or cytoreductive surgery,high intensity systemic chemotherapy,local radiotherapy and hyperthermic intraperitoneal chemotherapy.