The individual variability should be considered in precision medicine-prevention and treatment strategies.Medical research using genomics, proteomics, metabolomics, systems analyses, and other modern tools has made big progress.In 2002, the members of the Complex-Trait Consortium proposed to develop a new mouse genetics resource called the Collaborative Cross (CC).The CC is a genetic reference panel of recombinant inbred lines of mice, designed for the dissection of complex traits and gene networks.It will provide a powerful measure for functional studies of biological networks, which will be essential to understand the intricacies of disease processes.

Objective To assess the prevalence and binocular dysfunctional risk factors associated with asthenopia among adult myopes.Methods The study population included 800 adult myopes,a cross-sectional visual parameters that characterize the accommodative:accommodation amplitude (AA),accommodative facility,and accommodative response (fused crossed cylinder-FCC) and binocular function (near and distant horizontal and vertical associated phorias,near and distance negative and positive fusional vergence,near point of convergence,negative and positive relative accommodation (NRA/PRA),stimulus AC/A ratio and stereoacuity) were evaluated when these subjects wore adequate spectacle correction.Results Asthenopia was reported in 24.2％ (194/800) of myopes.The incidence of asthenopia in female (27.8％,128/460) was more than that in male (19.4％,66/340),and there was significant difference (P =0.006).In univariate analysis,the monocular AA,binocular AA,NRA and PRA were significantly associated with asthenopia (P =0.000).In multivariate analysis,low NRA (≤1.25 D),low NRA (≤1.50 D) were significant risk factors for asthenopia (P =0.000,OR =7.644 ;95％ CI 2.913-17.580;P =0.000,OR =5.303;95％ CI 2.822-16.205).Conclusion Preventive measures directed against the binocular dysfunctional risks factors associated with asthenopia may help reduce the prevalence and provide a positive impact on asthenopia.

Objective:To explore the clinical pathological characteristics and initial 131I curative responses of familial differentiated thyroid cancer (FDTC) and sporadic differentiated thyroid cancer (SDTC). Methods:A total of 66 FDTC patients (19 males, 47 females, age (39.8±11.7) years) and 1 701 SDTC patients (442 males, 1 259 females, age (40.9±11.3) years) who underwent 131I therapy in Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2010 and August 2018 were retrospectively enrolled. The clinical pathological characteristics, preablative stimulated thyroglobulin (ps-Tg), preablative stimulated thyroglobulin antibody (ps-TgAb) and response to initial therapy (excellent response, indeterminate response, biochemical incomplete response, structural incomplete response) of two groups were analyzed and compared. The clinical pathological parameters included age, gender, pathological type, tumour maximum diameter, bilateral, multifoci, nodules goiter, thyroiditis, thyroid membrane invasion, lymph node metastasis (LNM), invasion of the surrounding soft tissues, distant metastasis, TNM staging and American Thyroid Association (ATA) risk stratification (low-risk, intermediate-risk, high-risk). χ2 test or Fisher exact test and independent-sample t test were used to compare the data between two groups. Results:Comparing with SDTC group, FDTC group showed higher proportion of bilateral foci (45.5%(30/66) vs 31.2%(530/1 701); χ2=5.999, P=0.010), thyroid membrane invasion (43.9%(29/66) vs 26.6%(452/1 701); χ2=9.672, P=0.002) and distant metastasis (15.2%(10/66) vs 6.2%(105/1 701); χ2=8.418, P=0.004). There was a statistical difference in risk stratification between two groups (high-risk: 18.2%(12/66) vs 9.2%(156/1 701); intermediate-risk: 68.2%(45/66) vs 72.7%(1 237/1 701); low-risk: 13.6%(9/66) vs 18.1%(308/1 701); χ2=6.898, P=0.030). But the tumor maximum diameter of FDTC group was smaller than that of SDTC group ((1.24±0.74) vs (1.50±0.92) cm; t=-2.275, P=0.020). There were no significant differences in other clinical pathological parameters between FDTC group and SDTC group ( t=-0.804, χ2 values: 0.101-5.359, all P>0.05). There were no significant differences between two groups in the postoperation ps-Tg, ps-TgAb levels and the response to initial therapy after 131I treatment ( χ2 values: 0.059-1.915, all P>0.05). Conclusions:The FDTC group displays distinct characteristics as increased aggressiveness at diagnosis. But after accurately treatment, there is no significant difference in the response to therapy between two groups.

The poor prognosis of refractory thyroid cancer is the critical factor affecting the survival of patients with thyroid cancer. At present, multi-kinase inhibitors, surgery, particle implantation and other therapeutic methods are commonly used in clinical practice, which can improve the prognosis of patients to some extent, but the overall efficacy is still unsatisfactory. In recent years, immunotherapy has shown high efficacy, safety and reliability in the treatment of many tumors. In this article, the mechanism, current situation, method and prospect of immunotherapy in patients with refractory thyroid cancer are presented.

Atherosclerosis (AS) is a chronic and progressive arterial disease. It is an important cause of the occurrence and development of cardiovascular and cerebrovascular diseases. With the development of Traditional Chinese Medicine (TCM), TCM has many advantages in the therapy of AS, with less adverse reactions. Studies have shown that TCM can resist AS, and the mechanism mainly belongs to regulating lipid metabolism, anti-lipid peroxidation, anti-inflammation, anticoagulation, and protecting the structure and function of vascular endothelial cells. The mechanism of TCM for AS is warranted to be studied systematically, and the chemical components need to be further clarified.

Objective:The differentially expressed genes were screened from microarray data in the patients with non-syndromic craniosynostosis, and a protein interaction network was established to screen and predict hub genes related to the disease.Methods:The data set of GSE50796 were downloaded from the GEO database, which included seven samples of the closed cranial suture tissues from the non-syndromic craniosynostosis patients, and seven samples of the unclosed cranial suture tissues from the non-syndromic craniosynostosis patients. Analyze the differentially expressed genes were collected and analyzed with GEO2R, a GEO database online tool. P<0.05 and |logFC|> 2 were set as filter criteria. The ggplot2 of R package was applied for GO enrichment analysis, and the KEGG pathway analysis was completed with Enrichr. Gene set enrichment analysis (GSEA) was performed via GSEA 3.0 to analyze the correlation between gene sets and phenotypes. Secondly, the STRING database was used to analyze the interaction relationships between differentially expressed proteins in different tissues, and then Cytoscape and related plug-ins were used to establish the differentially expressed protein interaction network and screen the hub genes. Meanwhile, the key modules, important biological processes, and multiple co-expression relationships were analyzed. Results:A total of 255 differentially expressed genes based on the above screening conditions were obtained. The regulation of neural development screened by GO enrichment analysis, the PI3K-Akt signaling pathway screened by KEGG enrichment analysis, the important biological pathways (DNA replication, cell cycle, cytokine and receptor interaction) screened by GSEA enrichment analysis, and the positive regulation of osteoblast differentiation screened by ClueGO analysis, might be closely related to the etiology of non-syndromic craniosynostosis. The up-regulated hub genes such as CLEC12A, MS4A3 and DNTT in the group with closed sutures were screened by protein-protein interaction network and literature analysis, which might play a vital role in the pathogenic processes of non-syndromic craniosynostosis.Conclusions:With the multi-dimensional enrichment analysis of the differentially expressed genes and the establishment of protein interaction networks, we have deepened our understanding of differentially expressed genes, important biological processes and signaling pathways involved in the pathogenesis of non-syndromic craniosynostosis. The selected hub genes may become early diagnostic markers and potential molecular therapeutic targets.

Objective:The differentially expressed genes were screened from microarray data in the patients with non-syndromic craniosynostosis, and a protein interaction network was established to screen and predict hub genes related to the disease.Methods:The data set of GSE50796 were downloaded from the GEO database, which included seven samples of the closed cranial suture tissues from the non-syndromic craniosynostosis patients, and seven samples of the unclosed cranial suture tissues from the non-syndromic craniosynostosis patients. Analyze the differentially expressed genes were collected and analyzed with GEO2R, a GEO database online tool. P<0.05 and |logFC|> 2 were set as filter criteria. The ggplot2 of R package was applied for GO enrichment analysis, and the KEGG pathway analysis was completed with Enrichr. Gene set enrichment analysis (GSEA) was performed via GSEA 3.0 to analyze the correlation between gene sets and phenotypes. Secondly, the STRING database was used to analyze the interaction relationships between differentially expressed proteins in different tissues, and then Cytoscape and related plug-ins were used to establish the differentially expressed protein interaction network and screen the hub genes. Meanwhile, the key modules, important biological processes, and multiple co-expression relationships were analyzed. Results:A total of 255 differentially expressed genes based on the above screening conditions were obtained. The regulation of neural development screened by GO enrichment analysis, the PI3K-Akt signaling pathway screened by KEGG enrichment analysis, the important biological pathways (DNA replication, cell cycle, cytokine and receptor interaction) screened by GSEA enrichment analysis, and the positive regulation of osteoblast differentiation screened by ClueGO analysis, might be closely related to the etiology of non-syndromic craniosynostosis. The up-regulated hub genes such as CLEC12A, MS4A3 and DNTT in the group with closed sutures were screened by protein-protein interaction network and literature analysis, which might play a vital role in the pathogenic processes of non-syndromic craniosynostosis.Conclusions:With the multi-dimensional enrichment analysis of the differentially expressed genes and the establishment of protein interaction networks, we have deepened our understanding of differentially expressed genes, important biological processes and signaling pathways involved in the pathogenesis of non-syndromic craniosynostosis. The selected hub genes may become early diagnostic markers and potential molecular therapeutic targets.

Objective To study the pharmacological function of the aconitine in treating adjuvant arthritis(AA).Methods Fifty rats were randomly divided into the control group, AA model group, methotrexate group(0.5 mg/kg), and aconitine groups of different dosages (25, 100μg/kg). Except the control group, each group was injection of intradermal Freund's complete adjuvant (0.1 ml) into right hindpaw of rats to establish adjuvant arthritis model. On the 10th day after model onset, the aconitine were administered by gavage with 25, 100μg/kg once daily, and the methotrexate group was administered with 0.5 mg/kg methotrexate twice per week, and all groups were treated for 19 days. After the last administration, the foot swelling was measured by toe volume meter, arthritis index was calculated by 5-grade scoring method, spleen and thymus index were calculated, and the pathological changes of right ankle joint were observed by HE staining.Results After the model establishment, compared with the model group, the degree of swelling of the ankle at 20 days (668.7 ± 144.5μl, 566.9 ± 179.3μl vs. 912.1 ± 200.5μl), 24 days (833.1 ± 144.0μl, 803.9 ± 213.4μlvs.1069.5 ± 164.6μl) and 28 days (736.4 ± 115.0μl, 835.7 ± 170.1μlvs. 1107.2 ± 215.8μl) in the aconitine groups significantly decreased (P<0.05 orP<0.01). After the model establishment, compared with the model group, arthritic index scores at 18 days (3.1 ± 0.7, 3.2 ± 0.4vs. 3.8 ± 0.6), 24 days (3.1 ± 0.5, 3.4 ± 0.5vs.3.9 ± 0.3), 28 days (2.7 ± 0.6, 3.2 ± 0.9 vs. 4.0 ± 0.0) in the aconitine groups significantly decreased (P<0.05). Compared with the model group, the spleen index (3.5 ± 0.4, 3.3 ± 0.4, 4.0 ± 0.6vs.4.9 ± 0.5) respectively in the low and high dose group of aconitine and methotrexate group (P<0.01).Conclusion Aconitine has a certain degree therapeutic effect on AA rats.

Objective: To investigate the satisfaction and well-being of Chinese women with breast deficiency, and to analyze the relevant influencing factors. Methods: A cross-sectional study was conducted using a self-designed questionnaire to investigate the women with breast deficiency, visiting the Plastic Surgery Hospital of Chinese Academy of Medical Sciences from November 2013 to August 2018. The BREAST-Q BR (breast reconstruction) pre-operation and post-operation modules were used to assess the quality of life. Results: A total of 139 effective questionnaires were collected, including 83 patients before BR surgery and 56 post. There was no difference in quality of life in different ages, marital status, education levels, working status, and causes of breast deficiency. Mean scores of satisfaction with breasts, psychosocial well-being and sexual well-being of patients after breast reconstruction were significantly higher than those of patients without reconstruction (P=0.000), but there was no statistical difference in physical well-being-chest score. The physical well-being abdomen scores of patients with abdominal flap reconstruction was lower than that of the patients without reconstruction (P=0.007). With regard to analysis of specific items, compared with preoperative patients, patients with abdominal flap reconstruction reported lower scores in the items related to abdominal muscle weakness (P<0.05). Conclusions The breast deficiency resulting from Poland syndrome, breast cancer and other causes, can lead to a significant decrease in quality of life. Breast reconstruction can improve satisfaction with breast, psychosocial and sexual well-being in women with breast deficiency. The abdomen well-being of patients with abdominal flap reconstruction is decreased. Therefore, more attention should be paid to retain abdominal muscles to maintain abdominal shape and motor function during operation.

Objective:Tumor-treating fields (TTFields) is a kind of non-invasive anti-mitotic tumor therapy, which has been approved for patients with newly diagnosed and recurrent glioblastoma. This study aims to explore the efficacy and safety of TTFields in high-grade gliomas in clinical practice settings.Methods:The clinical data of 15 patients with recurrent glioma and 9 patients with newly diagnosed high-grade glioma admitted to our center from April 2019 to January 2021 were retrospectively analyzed. All patients accepted TTFields≥1 month. Follow-up was performed for 5.3 months (ranged from 2.3 to 10.7 months); Response Assessment in Neuro-Oncology Working Group (RANO) criteria was used to evaluate the glioma responses. The progression-free survival (PFS) and overall survival (OS) were calculated according to Kaplan-Meier method. Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0) and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Quality of life questionnaire-core 30 (QLQ-C30) and QLQ-brain cancer module (QLQ-BN20) questionnaires were used to evaluate the health-related quality of life (HRQoL). Treatment compliance was evaluated by data on the use of NovoTTF-200A devices, and calculated as a percentage of daily TTFields usage.Results:The median duration of TTFields was 4.2 months (ranged from 1.0 to 10.7 months), with a median compliance rate of 91.5% (67.0%-97.0%). TTFields was used alone in 2 patients and used with combination of chemotherapy in 22 patients. From follow-up to April 2021, 14 patients had stable symptoms and 10 had disease progression (8 died). The median PFS and OS of recurrent patients were 5.9 months ( 95%CI: 3.3-8.6 months) and 8.5 months ( 95%CI: 3.2-13.8 months), respectively; and the median PFS and OS of newly diagnosed patients were both 10.7 months (without 95%CI). The common adverse events included grading 1 dAE (58.3%) and grading 2 dAE (12.5%), without grading 3 or 4 dAE, manifested as contact or allergic dermatitis, erosion, folliculitis and ulcers. And 87.5% patients had stable HRQoL. Conclusions:The preliminary results showed that the survival of recurrent high-grade glioma patients treated by TTFields is similar to that reported in foreign literature; and the newly diagnosed patients need further survival follow-up. The patients' treatment compliance and safety are good. The dAE incidence (grading 1-2) is higher than that reported in the literature, and the toxicity was acceptable.