Development of a Risk Model and Genotyping Patterns Based on Disulfidptosis-Related lncRNAs to Predict Prognosis and Immune Landscape in Osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most prevalent orthopedic malignancy with a dismal prognosis. Disulfidptosis-related lncRNAs (DRLncs) may be related to the progression of OS, but their potential molecular regulatory role is still unclear. METHODS: Based on the data collected from The Cancer Genome Atlas (TCGA), we conducted correlation analysis and the univariate Cox analysis to screen prognosis-related DRLncs, followed by developing genotyping patterns and corresponding classifier. Subsequently, the survival analysis, enrichment analysis, drug sensitivity analysis and immune infiltration analysis were performed. Afterward, multivariate Cox regression was used to construct a risk model, which was further validated by the receiver operating characteristic (ROC) curve. The aberrant expression of hub DRLncs in OS was validated using the Reverse Transcription Polymerase Chain Reaction (RT-qPCR) assay. RESULTS: We identified 262 DRLncs and eleven prognosis-related DRLncs through filtering. We then constructed two distinct expression patterns of prognosis-related DRLncs and developed a classifier. We obtained 393 differentially expressed genes (DEGs) between different subtypes, which were significantly enriched in biological processes related to the extracellular matrix, integrin binding, focal adhesion, and Wnt signaling pathways. Through immune infiltration analysis, the activated CD4 memory T cells, resting natural killer (NK) cells, M1 macrophages, and resting dendritic cells (DC) were observed to exhibit different abundance in distinct subtypes. In the drug sensitivity analysis, tamoxifen showed a promising effect for drug-resistant OS. Furthermore, we identified five hub DRLncs and constructed a risk model. The RT-qPCR confirmed the aberrant expression of five hub DRLncs in OS. CONCLUSIONS: The present study identified DRLncs in OS, and conducted a comprehensive investigation of DRLncs-related expression patterns, survival status, immune landscape and drug sensitivity to reveal the difference in prognostic, pharmacological and immunological phenotype characteristics between distinct subtypes. Additionally, we developed a risk model to predict the prognosis, and constructed a genotyping classifier to predict the above phenotype characteristics in OS.

Radiotherapy dosimetry and radiotherapy related complications of immediate implant-based reconstruction after breast cancer surgery.

Backgrounds: The impact of immediate implant-based breast reconstruction (IBBR) on the delivery of radiotherapy plans remains controversial. This study aimed to compare the differences in radiotherapy dosimetry, complications of radiotherapy, and quality of life in patients who underwent modified radical mastectomy combined with or without IBBR. Methods: We retrospectively collected 104 patients with breast cancer who underwent intensity-modulated radiation therapy after modified radical mastectomy with IBBR (n =46) or not (n =58) from January 2017 to December 2021. The dosimetric differences in radiotherapy of planning target volume (PTV) and organs at risk and the differences in complications of radiotherapy between the two groups were compared. We also applied the functional assessment of cancer therapy-breast cancer (FACT-B) score to compare the difference in quality of life. The chi-square test and independent samples t-test were used to analyze the above data. Results: IBBR group was associated with higher PTV volumes, PTV D98, V95, and lower PTV Dmean, D2 compared with the non-reconstruction group (P<0.05). IBBR group also had lower radiotherapy dosimetric parameters in the ipsilateral lung and the heart of left breast cancer patients. The differences in the rates of radiation pneumonia (RP) and radiation dermatitis (RD) between the two groups were not statistically significant (P > 0.05). Moreover, FACT-B scores at 6 months after radiotherapy in patients with IBBR were higher than those without reconstruction (P < 0.05). Conclusion: Patients with IBBR achieved better radiation dosimetry distribution and higher quality of life without more complications of radiotherapy.

Sensitization of cervical cancer cells to radiation by the cyclin-dependent kinase inhibitor dinaciclib.

Dinaciclib is a selective cyclin-dependent kinase inhibitor, but its radiosensitizing effect remains unclear. The aim of this study is to investigate the radiosensitizing effect of Dinaciclib on cervical cancer cells. Two cervical cancer cell lines, Hela and Siha, were selected, and the IC50 was determined by CCK8. The radiosensitizing effect of Dinaciclib was verified by plate cloning assay, and the G2/M phase arrest and apoptosis of IR cells were verified by flow cytometry. Immunofluorescence assay was used to verify the formation of γH2AX foci following DNA damage. Western blot was performed to detect cell cycle, apoptosis, autophagy, and DNA damage-related pathways. Dinaciclib increased the cell sensitivity to IR. IR induced G2/M phase arrest and apoptosis, and Dinaciclib enhanced this effect. Further, Dinaciclib delayed DNA repair, including non-homologous end joining repair and homologous recombination repair, and reduced the expression of DNA repair proteins Ku80 (SiHa cells), Ku70, and RAD51, as well as the expression of apoptotic marker Bcl-2. The expression of autophagy marker Beclin1 induced tumor cell death and increased the formation of DNA damage marker γH2AX foci. Dinaciclib improves the sensitivity of cervical cancer cells to IR by inducing cell cycle arrest, delaying DNA repair, and increasing apoptosis. However, further research is needed to unravel the complexity of DNA repair pathways.

Study on the effect of CYP2C19 genetic polymorphism and plasma concentration on clopidogrel resistance.

At present, the mechanism for clopidogrel resistance (CR) is incompletely understood. Here, we aimed to analyze of the association of plasma concentration of clopidogrel active metabolites (CAM) and CYP2C19 genetic polymorphism with CR. We assigned 77 patients to receive CLP at a loading dose of 300mg on day 1, followed by 75mg per day from day 2 to day 6. Three peripheral venous blood samples were collected for analysis. Our results showed that plasma concentration of CAM in extensive metabolizers (EMs) group (2.48(1.31, 5.67) ng/mL) was higher than that in intermediate metabolizers (IMs) group (1.44(1.18,3.55) ng/mL) and that in poor metabolizers (PMs) (1.18(1.12,1.33) ng/mL) group was the lowest (H=14.58, P=0.001). Besides, the incidence of CR in EMs group(11.1%) was lower than that in IMs group (20.0%) and that in IMs group was lower than that in PMs group (45.5%) (χ2=6.344, P=0.042). In addition, our findings confirmed that the incidence of chest tightness in IMs group (40.0%) and PMs group (50.0%) was higher than that in EMs group (9.1%) (P=0.015). Over the follow-up period, it was found that CYP2C19 and plasma concentration of CAM were related to the incidence of chest tightness. Our findings indicated that in addition to CYP2C19, plasma concentration of CAM may be an important factor in predicting CR.

[Outcomes and prognostic factors of distant metastasis in patients with advanced cervical squamous cell carcinoma treated with concurrent chemoradiotherapy].

OBJECTIVE: To evaluate the outcomes and prognostic factors of distant metastasis in patients with advanced cervical squamous cell carcinoma treated with concurrent chemoradiotherapy (CCRT). METHODS: A total of 118 patients with International Federation of Gynecology and Obstetrics (FIGO, 2009 version) stage II b-IVa cervical squamous cell carcinoma treated with CCRT between 2006 and 2010 in the Second Affiliated Hospital of Dalian Medical University were analyzed. Their median age was 48 years (range, 23-70 years). FIGO stages were as follows: IIb stage 56 cases, IIIa stage 6 cases, IIIb stage 52 cases, and IVa stage 4 cases. Of the all patients, 55 cases showed bulkly tumor (tumor size >4 cm) and 35 cases were pelvic lymph node positive. Forty patients had pretreatment hemoglobin (Hb) levels no greater than 110 g/L. Patients with elevated squamous cell carcinoma antigen (SCC- Ag) >1.5 µg/L before CCRT and at one month after CCRT were 91 cases and 34 cases, respectively. Kaplan-Meier method was used to estimate survival. For the analysis of prognostic factors affecting distant metastasis, log- rank test was used for univariate analysis, and Cox proportional hazard model was used for multivariate analysis. RESULTS: Thirty- seven patients were diagnosed with recurrence, 19 cases of whom developed distant metastasis, 13 cases developed loco-regional recurrence and 5 cases had both distant and loco-regional recurrence. The 5- year overall survival rates and distant disease- free survival of all patients were 64.0% and 78.8% , respectively. Two patients had grade 3 acute gastrointestinal toxicity (mainly diarrhea) and 20 cases had grade 3 to 4 hematologic toxicity. Seven patients experienced grade 3 to 4 late toxicity, 5 cases of them were gastrointestinal and 2 cases were genitourinary toxicity. Univariate analysis showed that FIGO stages, SCC-Ag level at one month after treatment, pretreatment hemoglobin level, and pelvic lymph node metastasis were significantly correlated with distant metastasis (all P < 0.05). Multivariate analysis showed that FIGO stage, SCC- Ag level at one month after treatment, and pelvic lymph node metastasis were independent prognostic factors for distant metastasis (all P < 0.05). CONCLUSIONS: For stage IIb-IVa cervical squamous cell carcinoma, the regimen of CCRT was efficacious and safe. The predictive factors for distant metastasis in patients with IIb-IVa stage squamous cell carcinoma of cervix treated with CCRT included FIGO stage, SCC- Ag level at one month after treatment, and pelvic lymph node metastasis. New treatment strategies should be considered to control distant metastasis for these patients.

The radiation-sensitizing effect of flavopiridol in the esophageal cancer cell line Eca109.

Flavopiridol is a cyclin-dependent kinase inhibitor. It has shown an antitumor effect against several cancers. In the present study, the radiation-sensitizing effect of flavopiridol was investigated in an esophageal squamous carcinoma cell line, Eca109. The growth inhibitory rate of Eca109 with flavopiridol was determined using the MTT and the radio-sensitizing rate using clonogenic survival assays. The cell cycle distribution and the rate of apoptosis were measured using flow cytometry. The proteins cyclin D1, ERK/pERK, caspase-3, Bax and Bcl-2 were detected using western blot analysis to elucidate the mechanism of the radiosensitization effect. MTT assay showed that flavopiridol inhibited the survival rate of Eca109 cells and the effect was dose-dependent. Its IC50 was 193.3 nmol/l. The result of the clonogenic survival revealed that flavopiridol enhanced the radiosensitivity of Eca109 cells and the sensitization enhancement ratio (SER) was 1.194 at 0.2×IC50. Moreover, we detected that the cells treated with flavorpiridol were arrested at the G2/M phase and the apoptosis caused by radiation was increased. In addition, the proteins caspase-3 and Bax in cells treated with flavopiridol were upregulated, while cyclin D1 and Bcl-2 were downregulated. In conclusion, flavopiridol may enhance the radiosensitivity of Eca109 cells and the radiosensitizing effect of flavopiridol may be mediated by decreasing the levels of the cyclin D1 protein, thus increasing the percentage of cells at G2/M phase.

[Present situation of congenital defects in five counties (cities) of Gansu province in 2009 - 2010].

OBJECTIVE: To understand the situation of congenital defects' in five counties/cities in Gansu province so as to provide scientific evidence for the development of effective interventions. METHODS: General information was collected on all the neonates who were born in Dunhuang city, Jingchuan county, Hui county, Weiyuan county and Yongjing county in Gansu province between Oct. 1(st), 2009 to Sep. 30(th), 2010, with all of their gestational age above 28 weeks. Neonates would include live birth, dead fetus and still birth. RESULTS: The overall incidence of congenital defects was 7.49‰ in the five counties/cities in Gansu province in 2009. Ranking order in the top three showed as congenital heart disease, pigmented nevus and limb deformity. Disease with the highest mortality was congenital heart disease (0.79‰). The incidence of congenital defects was 8.35‰ in 2010 with the ranking order of the top three as congenital heart disease, neural tube defects/pigmented nevus and hydrocephalus. Diseases having the highest mortality was congenital heart disease (1.10‰). Different incidence rates on congenital defects were seen in related areas, with the highest incidence as 14.65‰ in Dunhuang city. Hui county had the lowest incidence-3.28‰. CONCLUSION: Different incidence of congenital defects were seen in respective areas in Gansu province, with the change of ranking orders. Different strategies should be developed differently depending on the current states of congenital defects in respective areas, according to the three-grade prevention model, to reduce the occurrence of congenital defects.