Cancer is one of the major diseases of high morbidity and mortality worldwide,and its therapeutic approaches are facing great challenges.Immunotherapy,especially the activation of innate immunity represented by the cGAS-STING signaling pathway,is the current research hotspot in tumor immunotherapy.Activation of innate immune response by gas therapy is the latest development in tumor therapeutic approaches,especially the use of gas signaling molecules(NOx CO,H2S and SO2)to activate the cGAS-STING signaling pathway to induce intrinsic immunity of the organism,which leads to anti-tumor immunotherapy.Although intrinsic immunity activated by gas signaling molecules plays an important role in tumor immunotherapy,few reviews have been reported on its association with the cGAS-STING signaling mechanism.In this paper,we will comprehensively describe how gas signaling molecules damage the mitochondrial matrix and DNA damage through oxidative/nitrosative stress,thereby activating the cGAS-STING signaling pathway and triggering the innate immune cascade,aiming to summarize the process of activation of anti-tumor immune effects by gas signaling molecules,and to provide more references for the gas therapies in the future anti-tumor immunity research.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Cancer is one of the major diseases of high morbidity and mortality worldwide,and its therapeutic approaches are facing great challenges.Immunotherapy,especially the activation of innate immunity represented by the cGAS-STING signaling pathway,is the current research hotspot in tumor immunotherapy.Activation of innate immune response by gas therapy is the latest development in tumor therapeutic approaches,especially the use of gas signaling molecules(NOx CO,H2S and SO2)to activate the cGAS-STING signaling pathway to induce intrinsic immunity of the organism,which leads to anti-tumor immunotherapy.Although intrinsic immunity activated by gas signaling molecules plays an important role in tumor immunotherapy,few reviews have been reported on its association with the cGAS-STING signaling mechanism.In this paper,we will comprehensively describe how gas signaling molecules damage the mitochondrial matrix and DNA damage through oxidative/nitrosative stress,thereby activating the cGAS-STING signaling pathway and triggering the innate immune cascade,aiming to summarize the process of activation of anti-tumor immune effects by gas signaling molecules,and to provide more references for the gas therapies in the future anti-tumor immunity research.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Objective To investigate the effects of metformin on cell proliferation in differentiation degree of endometrial carcinoma cells and related mechanisms. Methods The endometrial cancer cell lines Ishikawa and AN3CA were used. Cell proliferation was assessed after exposure to metformin with or without epithelial growth factor receptor (EGFR) inhibitor AG1478 by cell counting kit-8 (CCK-8) method. EGFR mRNA was determined by reverse transcription (RT)-PCR. The expression of phosphorylation EGFR (p-EGFR) and total EGFR (t-EGFR) and phosphorylation extracellular signal-regulated kinase 1/2 (p-ERK1/2) and total ERK1/2 (t-ERK1/2) were examined by western blot. Results (1)CCK-8 experiment showed that metformin could inhibit the proliferation of endometrial cancer cells in a time-dependent manner and a dose-dependent manner (P<0.05), but the inhibition of well differentiated cell line Ishikawa was lower than that in poorly differentiated cells AN3CA (P<0.05). AG1478 also could inhibit the proliferation of endometrial cancer cells in a time-dependent manner and in a dose-dependent manner (P<0.05), but the inhibition rate of well differentiated cell line Ishikawa was higher than that in poorly differentiated cells AN3CA (P<0.05). Metformin+AG1478 also could inhibit the proliferation of endometrial cancer cells in a time-dependent manner and in a dose-dependent manner (P<0.05), and the inhibition of combined with metformin and AG1478 was stronger than that with a single application of drugs, but the inhibition rate of Ishikawa was higher than that in AN3CA (P<0.05).(2)RT-PCR method showed that different concentrations of metformin (0.01, 0.1, 1, 5, 10 mmol/L, respectively) for 24 hours, the expression level of EGFR mRNA in Ishikawa cells were respectively 0.74±0.03, 0.61±0.04, 0.46±0.03, 0.31±0.03 and 0.23±0.03, the expression level of EGFR mRNA in AN3CA cells were respectively 0.79±0.20, 0.61±0.03, 0.50±0.05, 0.32±0.03 and 0.26 ± 0.04, the inhibition effect showed a significant concentration-dependent manner (all P<0.01). (3) Western blot method displayed that the effect of metformin treated respectively 2, 4, 6 or 8 hours, there were not significant difference in the expression levels of t-EGFR protein and t-ERK1/2 between Ishikawa and AN3CA cells (all P>0.05). But the expression levels of p-EGFR and p-ERK1/2 protein were significantly lower between two groups (P<0.01), which showed a time-dependent manner(P<0.01). Conclusion Metformin could inhibit the proliferation of endometrial cancer cells, the inhibition is associated with the differentiation degree of cancer cells. Metformin could enhance the EGFR signaling pathway inhibitor AG1478 inhibition of endometrial cancer cells, which may inhibit EGFR expression of phosphorylated proteins to inhibit the phosphorylation of ERK1/2 proteins and then inhibit proliferation of endometrial cancer cells.

Objective To explore the relation between the behavior psychology analysis of partial me-chanical injuries and the nature of death in high-falling cases, and provide reference, for such cases. Methods Of 311 death victims of high-falling injuries collected from 2008 to 2013, 205 cases were as-sociated with partial mechanical injuries. The characteristics of injury formation, preliminary crime scene traces, fatal injury of high-falling, and text messages were all retrospectively analyzed. Results Accord-ing to the investigation of preliminary crime scene traces, fatal injury of high-falling and text message, there were 86 suicide, 24 accident and 95 uncertainty in the 205 cases. According to the behavior psy-chology analysis of partial mechanical injuries, there were 80 suicide, 11 accident, and 4 homicide in the 95 uncertainty cases. Conclusion The partial mechanical injuries uncertainly caused by high-falling correlate with the manner of high-falling death. According to the behavior psychology analysis of the partial mechanical injuries in high-falling death cases, the presumption of high-falling death is usually accurate.

Objective To evaluate vitamin D status of the middle and old aged women in the urban area of Guiyang,and to explore the impact of vitamin D status on the bone mineral density.Methods A total of 511 healthy women,aged 40 to 79 years old,living in one of the urban communities in Guiyang,were selected by means of stratified cluster sampling.The levels of serum 25-hydroxyvitamin D [25 (OH) D] and intact parathyroid hormone (iPTH) were detected by radioimmunoassay.In addition,the bone mineral density (BMD) of hip,lumbar vertebrae 1-4 (L1-4),and neck of left femur were detected by Dual energy X ray absorptiometry.Results The average serum level of 25(OH)D in all subjects was (21.3 ± 7.9) ng/ml and that of iPFH was (29.3 ± 16.5) pg/ml.Severe deficiency [25 (OH) D＜ 10 ng/ml],deficiency [10 ≤ 25 (OH) D＜20 ng/ml],insufficiency [20 ≤ 25 (OH) D ≤ 30ng/ml],and sufficiency [25 (OH) D＞ 30 ng/ml] of vitamin D were ascertained in 5.3％,42.3％,37.9％,and 14.5％ of the total cases respectively.The morbidity of secondary hyperparathyroidism was 4.7％.The level of 25 (OH) D was positively correlated with the BMD of L1-4 and neck of left femur (both P＜0.01).The level of iPTH was negatively correlated with BMD of neck of left femur and L1-4 (both P＜0.05).Conclusion The majority of middle and old aged women in the urban area of Guiyang city were found to be of vitamin D deficiency and insufficiency.Vitamin D status is positively correlated with BMD at lumbar spine and proximal femur.Serum 25 (OH) level below 20 ng/ml is associated with raised parathyroid hormone,which increases the risk of osteoporosis.

Objective To evaluate vitamin D status in healthy adults living in Guiyang. Method 1 500 healthy volunteers aged 20-79 years ( mean 45.2 years ) were recruited from a community in Guiyang by cluster sampling method. Questionnaires for living habits and fasting blood samples were collected from November, 2009 to February, 2010. Serum 25 ( OH ) D concentrations were measured by radioimmunoassay, using the DiaSorin kit,USA. Results The average serum 25 ( OH ) D level was ( 20. 4±9.0 ) ng/ml. The percentages of vitamin D deficiency [25 ( OH ) D ＜ 20 ng/ml], insufficiency [20 ng/ml ≤ 25 ( OH ) D ＜ 30 ng/ml], and sufficiency [25 ( OH ) D ≥ 30ng/ml] were 52. 3% , 32. 3% , and 15.4% , respectively. The 25 (OH) D concentrations in the young, middle-aged,and elderly were ( 18. 2±9. 2), (22. 8±8. 7), and ( 19. 9±7.8) ng/ml, respectively. The percentages of vitamin D deficiency in these groups were 62. 8%, 40. 2%, and 55.4%, being 61.6% in higher educational group ( ≥ 13 years) and 64. 4% in the group with lower body mass index ( ＜ 18.5 kg/m2 ). Conclusion Vitamin D deficiency is common in Guiyang including all age groups, especially among the youth and the elderly. Serum 25-hydroxyvitamin D level is also influenced by education, age, smoking, and other factors.