Thyroid carcinoma is one of the malignant tumors with rapidly increasing incidence rates. Some refractory patients face challenges from drug toxicity and resistance, urgently requiring the discovery of new therapeutic pathways to improve prognosis. Regulatory cell death（RCD）is a highly regulated orderly death mode, including apoptosis, necroptosis, pyroptosis, ferroptosis, and cuproptosis. Recent studies have found that RCD is closely associated with tumor progression, invasion, and resistance. This article systematically reviewed various death modes in thyroid cancer, including the core signaling nodes of each death pathway, and explored their specific functions in tumor progression. It also summarized potential therapeutic strategies targeting these death pathways. However, the complexity of RCD mechanisms and the sensitivity of treatments remain controversial. Future efforts should focus on screening broad-spectrum targets and developing synergistic therapies to ultimately achieve precise treatment based on cell death, thereby improving the prognosis of refractory thyroid cancer.

BACKGROUND:For the replacement treatment of long-segment tracheal defects,although tissue engineering research has made some progress in recent years,it is still not perfect,and one of the biggest difficulties is that the hemodynamic reconstruction of the tracheal replacement cannot be achieved rapidly. OBJECTIVE:To preliminarily explore the potential of polycaprolactone scaffolds modified with exosome-loaded hydrogels to construct a rapidly vascularized tracheal substitute. METHODS:Exosomes were extracted from bone marrow mesenchymal stem cells of SD rats.After preparation of hyaluronic acid methacrylate solution,the exosome solution was mixed with hyaluronic acid methacrylate solution at a volume ratio of 1:1.Hyaluronic acid methacrylate hydrogels loaded with exosomes were prepared under ultraviolet irradiation for 5 minutes.The degradation of exosome-unloaded hydrogels and the controlled release of exosome-loaded hydrogels were detected.Polycaprolactone scaffolds were prepared by 3D printing.The pure hyaluronic acid methacrylate solution and the exosome-loaded hyaluronic acid methacrylate solution were respectively added to the surface of the scaffold.Hydrogel-modified scaffolds and exosome-modified scaffolds were obtained after ultraviolet irradiation.Thirty SD rats were randomly divided into three groups with 10 rats in each group and subcutaneously implanted with simple scaffolds,hydrogel-modified scaffolds and exosome-modified scaffolds,respectively.At 30 days after surgery,the scaffolds and surrounding tissues of each group were removed.Neovascularization was observed by hematoxylin-eosin staining and Masson staining and the expression of CD31 was detected by immunofluorescence. RESULTS AND CONCLUSION:(1)As time went by,the hydrogel degraded gradually,and the exosomes enclosed in the hydrogel were gradually released,which could be sustained for more than 30 days.The exosome release rate was faster than the degradation rate of the hydrogel itself,and nearly 20%of the exosomes were still not released after 30 days of soaking.(2)Under a scanning electron microscope,the surface of the simple polycaprolactone scaffold was rough.After hydrogel modification,a layer of gel was covered between the pores of the scaffold,and the scaffold surface became smooth and dense.(3)After 30 days of subcutaneous embedding,hematoxylin-eosin staining and Masson staining showed that more neovascularization was observed inside the scaffolds of the exosome-modified scaffold group compared with the hydrogel-modified scaffold group.The hydrogels on the scaffolds of the two groups were not completely degraded.Immunofluorescence staining showed that CD31 expression in the exosome-modified scaffold group was higher than that in the hydrogel-modified scaffold group(P<0.000 1).(4)These results indicate that hyaluronic acid methacrylate hydrogels can be used as controlled-release carriers for exosomes.The 3D-printed polycaprolactone scaffold modified by hyaluronic acid methacrylate hydrogel loaded with exosomes has good biocompatibility and has the potential to promote the formation of neovascularization.

【Objective】 To evaluate the expression of GAB1 in ER-positive breast cancer and its effect on MCF-7 cells’ metastasis. 【Methods】 The expression of GAB1 in ER-positive breast cancer tissues was detected by immunohistochemistry. We analyzed the relationship of GAB1 expression with the patients’ clinicopathological features and prognosis. The invasion and metastasis abilities of MCF-7 cells after silencing GAB1 expression were observed by Transwell assay. The effect of GAB1 expression on the EMT of breast cancer cells was analyzed by Western blotting. 【Results】 Immunohistochemical staining showed that GAB1 expression had significant correlation with lymph node metastasis(P=0.014) and stage(P=0.011). Transwell results showed that shGAB1 significantly inhibited the migration and invasion of human breast cancer MCF-7 cells. Western blotting results showed that shGAB1 significantly increased E-cadherin expression and decreased Vimentin expression. Kaplan-Meier analysis revealed that ER-positive breast cancer patients with high GAB1 expression tumors had a significantly worse relapse-free survival rate than those with low GAB1 expression tumors(P<0.001). Multivariate analysis showed that stage and GAB1 expression were independent predictors of survival. 【Conclusion】 GAB1 is highly expressed in ER-positive breast cancer. ShGAB1 expression can inhibit the migration, invasion and EMT of breast cancer cells. GAB1 might be used as one of the valuable markers for prognosis in patients with ER-positive breast cancer.

Objective:To analyze the relationship between maternal mutations in basal core promoter region of hepatitis B virus (HBV) genotype C and intrauterine transmission.Methods:We collected information on general demographic characteristics and process of delivery among 399 pairs of consecutive HBsAg-positive mothers and their neonates, from the Third People’s Hospital of Taiyuan in Shanxi province, China. Fluorescence quantitative polymerase chain reaction (FQ-PCR) and Electro-chemiluminescence immuno-assay (ECLIA) kits were used to detect both maternal and neonatal HBV DNA and serological markers in the peripheral blood. From 113 mothers with HBV DNA load ≥10 6 IU/ml, we selected 22 mothers whose neonates were with intrauterine transmission and randomly selected the same number of mothers whose neonates were without intrauterine transmission, as controls. The whole-length HBV DNA were extracted, amplified, cloned, sequenced and genotyped. Finally, a total of 39 mothers with genotype C of HBV were selected for mutation analysis. Results:Thirty-nine cases of genotype C (88.63 %) were finally included in the study, with 19 cases in the intrauterine transmission group and 20 cases as controls. Rates of A1762T/G1764A double mutations were significantly different between the intrauterine transmission group and the control group (7.53 % vs. 27.72 %, P<0.001). Results from the multivariate analysis showed that the A1762T/G1764A double mutations had reduced the risk of intrauterine transmission (a OR=0.065, 95 %CI: 0.006-0.746, P=0.028). Maternal A1762T/G1764A double mutations appeared to be possibly associated with neonatal HBeAg ( P=0.050). Conclusion:A1762T/G1764A double mutations of HBV DNA from the genotype C of those HBsAg-positive mothers could reduced the risk of HBV intrauterine transmission during pregnancy.

OBJECTIVE： To investigate the effects of Dendrobium officinale polysaccharides on gene expression profile of HUVEC. METHODS： HUVEC was selected as objects. MTS method was used to detect the effects of different doses of D. officinale polysaccharides （50， 100， 200， 400， 800 μg/mL） on the proliferation activity of HUVEC. The growth inhibitory concentration of 30％ cells （IC30） was calculated to screen the dose of follow-up tests. cDNA microarray assay was used to detect the changes of gene expression profile for HUVEC after treated with D. officinale polysaccharides for 24 h， so as to screen differentially expressed genes. GO enrichment analysis and KEGG pathway enrichment analysis were performed for top 5 differentially expressed genes by using DAVID bioinformatics resource database. Real-time fluorescence quantitative polymerase chain reaction （qRT-PCR） was used to validate the results of microarray detection with immunity-related differentially expressed genes as objects. RESULTS： After treated with 100， 200， 400， 800 μg/mL D. officinale polysaccharides， survival rate of HUVEC  were decreased significantly （P＜0.05 or P＜0.01）. IC30 value was 408 μg/mL. After treated with 400 μg/mL （by IC30） D. officinale polysaccharides， there were 91 differentially expressed genes in HUVEC cells， of which 84 were up-regulated and 7 were down-regulated. Top 5 genes of up-regulated and down- regulated expression were SELE， CCL2， CXCL6， IL8， ICAM1 as well as VWCE， CPT1A， CLU， CCL14， CINS4， which may be mainly associated with immune conditions and inflammatory responses. The differentially expressed genes mainly distributed in extracellular domain， and were enriched in biological processes such as production and response of cytokines and stimulus response， and played molecular functions such as chemokine and its receptor activity. The up-regulated genes as SELE， ICAM1 and CXCL2 were mainly enriched in TNF signaling pathway， influenza A （H1N1）， herpes simplex virus infection and other pathways. The down-regulated gene CCL14 was mainly enriched in chemokine signaling pathway. Results of qRT-PCR validation tests showed that relative expression of ICAM1 was increased significantly， while that of CCL14 was decreased significantly （P＜0.05）， which was in agreement with microarray detection results. CONCLUSIONS： After treated with D. officinale polysaccharides， the expression of 91 genes in HUVEC cells are different significantly， mainly being up-regulated. The differentially expressed genes may participate in immune regulation through TNF signaling pathway， influenza A （H1N1） and herpes simplex virus infection.

[Abstract] Objective: To investigate the relationship between expression of MICA/B (MHC class I chain-related proteinA/B) and disease-free survival (DFS) of patients with HER2+(human epidermal growth factor receptor 2) breast cancer tissue. Methods: Twenty six cases of corresponding para-cancerous tissue and 100 cases of HER2+ breast cancer tissue that preserved in wax at Zhengzhou People’ s Hospital Affiliated to Southern Medical University from January 2009 to June 2010 were collected for this study. Expression of MICA/ B in these tissue samples was detected by immunohistochemistry; and the relationship between MICA/B expression with clinicopathologic features as well as DFS was analyzed with Kaplan-Meier survival curve. Results: The expression of MICA/B in adjacent paracancerous tissues was negative (0/26), however, it was highly positive in cancer tissues (92/100), and the percentage with high expression was 65%(65/100), the difference was significant (P<0.05). High MICA/B expression rate in stage I was significantly higher than that in stage Ⅱ-Ⅲ (77.55% vs 52.94%， P<0.05), and the high expression rate in stage T1 was also significantly higher than that in stage T2-T4 (75.00% vs 52.27%， P<0.05). High MICA/B expression rate in ER+, PR+ group (with positive number≥1%) was significantly lower than that in ER- , PR-group (ER： 52.38% vs 74.14%，PR： 51.35% vs 73.02%， all P<0.05). MICA/B expression was correlated with clinical stages, the expression of ER, PR and tumor size (all P<0.05), but not associated with menopausal status, histological grade and lymph node metastasis (all P>0.05). Over-expression of MICA/B was closely associated with much better 6-year DFS rate in patients no matter with or without targeted therapy (the targeted group: 90.6% vs 72.2%; the untargeted group: 78.4% vs 58.8%, all P<0.05). Conclusion: Over-expression of MICA/B in HER2+ breast cancer tissue is closely related to DFS, which may be served as a potential prognosis indicator for patients with HER2+ breast cancer.

Objective To explore the clinical value of transvaginal color Doppler ultrasound in the differential diagnosis of rupture of ectopic pregnancy and rupture of corpus luteum.Methods A total of 42 patients with rupture of ectopic pregnancy and 42 patients with rupture of corpus luteum were selected and treated with transvaginal color Doppler ultrasound and two-dimensional ultrasound examination respectively.Results Two-dimensional ultrasound showed no significant value in differential diagnosis of rupture of ectopic pregnancy and rupture of corpus luteum,but transvaginal color Doppler ultrasound showed a definite value in diagnosis rupture of ectopic pregnancy and rupture of corpus luteum.There were significant differences in blood flow performance,blood flow spectrum and blood flow parameters by transvaginal color Doppler ultrasound between rupture of ectopic pregnancy and rupture of corpus luteum (P ＜ 0.05).Conclusion Application of transvaginal color Doppler ultrasound can be used for the diagnosis of rupture of ectopic pregnancy and rupture of corpus luteum.

Objective To explore the clinical value of transvaginal color Doppler ultrasound in the differential diagnosis of rupture of ectopic pregnancy and rupture of corpus luteum.Methods A total of 42 patients with rupture of ectopic pregnancy and 42 patients with rupture of corpus luteum were selected and treated with transvaginal color Doppler ultrasound and two-dimensional ultrasound examination respectively.Results Two-dimensional ultrasound showed no significant value in differential diagnosis of rupture of ectopic pregnancy and rupture of corpus luteum,but transvaginal color Doppler ultrasound showed a definite value in diagnosis rupture of ectopic pregnancy and rupture of corpus luteum.There were significant differences in blood flow performance,blood flow spectrum and blood flow parameters by transvaginal color Doppler ultrasound between rupture of ectopic pregnancy and rupture of corpus luteum (P ＜ 0.05).Conclusion Application of transvaginal color Doppler ultrasound can be used for the diagnosis of rupture of ectopic pregnancy and rupture of corpus luteum.

Objective To evaluate the clinical value of Chinese Multi-Dimensional Health Assessment Questionnaire (MDHAQ-C) in patients with rheumatoid arthritis (RA). Methods From December 2015 to October 2016,four hundred and twelve RA patients were recruited in this study and completed the MDHAQ-C independently and routine assessment of patient index data 3 (RAPID3) was calculated. Then correlations were assessed by Spearman correlation coefficient of RAPID3 with indices of clinical relevance and disease activity to evaluate its clinical values. Results MDHAQ-C is moderately correlated with ESR (r=0.399), CRP (r=0.381), SJC (r=0.499), TJC (r=0.558) (P<0.01), but highly correlation with VAS of pain (r=0.836), VAS of global status (r=0.915) and overall assessment of physician (r=0.784)(P<0.01), and highly correlated with a Spearman's coefficient of 0.784 for DAS 28-ESR, 0.734 for CDAI and 0.682 for SDAI (P<0.001). Conclusion MDHAQ is a reliable, valid instrument for disease activity assessment and a feasible index for clinical settings in Chinese RA patients.