Objective To explore the value of diffused optical tomography(DOT)with ultrasonography (US)in differential diagnosis of breast benign from malignant neoplasms.Methods One hundred ard twenty-three breast neoplasms from 113 patients were checked use the optical tomography image ultrasonography(OPTIMUS).The diagnosis results of the system were compared with pathological study.Two-dimensional ultrasound features in breast neoplasms were digitalizated,and HBT and SO_2 were detected by DOT.At last,synthesis diagnostic index(SDI)was obtained by both US and DOT.Statistic process was carried out in sensitivity,specificity,and the rate of accuracy respectively by US,DOT and OPTIMUS system.Results Among breast neoplasms of 123 mass studied pathologically,78 of them were benign and the rest were malignant.HBT in benign lesions(153.02±105.78)was significantly less than malignant lesions(232.95±78.22),SO_2 in benign lesions(1.0332±0.1641)was significantly elevated compared with malignant lesions(0.8794±0.1814),SDI in benign lesions(147.26±53.76)was significantly less than malignant lesions(243.98±57.27),significant differences were found between the two groups(P＜0.05).The sensitivity of differential diagnosis of breast neoplasms by the OPTIMUS system was 93.33%,the specificity was 83.33%,and the rate of accuracy was 86.99%.Conclusions OPTIMUS can improve the specificity and the rate of early diagnosis.

Objective:To investigate the correlation of centromere protein K (CENPK) expression in triple-negative breast cancer (TNBC) with epithelial-mesenchymal transformation (EMT) and its clinical significance.Methods:Immunohisochemical SABC method was used to detect the expressions of CENPK and EMT-related proteins (E-cadherin, Vimentin and N-cadherin) in 69 specimens of TNBC and cancer-adjacent tissues collected from patients in Binzhou People's Hospital Affiliated to Shandong First Medical University from January 2015 to December 2018. The correlations of CENPK expression with clinicopathological characteristics of patients and expressions of EMT-related proteins were analyzed.Results:The positive expression rates of CENPK in TNBC and cancer-adjacent tissues were 72.46% (50/69) and 14.49% (10/69), respectively, and the difference was statistically significant ( χ2 = 47.18, P<0.001). The CENPK expression in TNBC was related to pathological grade, clinical stage and lymphatic metastasis (all P<0.05). The CENPK expression in TNBC was negatively correlated with E-cadherin expression ( r = -0.447, P<0.01), but positively correlated with Vimentin and N-cadherin expressions ( r values were 0.503 and 0.415, both P<0.01). The median overall survival time of CENPK high-expression group was 24 months (95% CI 10-39 months), while that of CENPK low-expression group was 42 months (95% CI 19-50 months). The difference in overall survival between the two groups was statistically significant ( χ2 = 7.36, P = 0.016). Conclusions:CENPK may be involved in the occurrence and development of TNBC through EMT, and the expression of CENPK may be related to the prognosis of patients.

Objective:To investigate the expressions of tissue inhibitor of matrix metalloproteinase-1 (TIMP1) and fibronectin 1 (FN1) in pregnancy associated breast cancer (PABC) and their correlations with expression of E-cadherin (E-cad).Methods:The clinicopathological data of 55 PABC patients in Binzhou People's Hospital Affiliated to Shandong First Medical University from January 2011 to December 2020 were retrospectively analyzed. Immunohistochemistry was used to detect expressions of TIMP1, FN1 and E-cad in cancer tissues and corresponding paracancerous tissues (>3 cm from the edge of the tumor foci). The expressions of TIMP1 and FN1 proteins in fresh intraoperative frozen cancer tissues and paracancerous tissues of 10 PABC patients were detected by Western blotting. The correlations of TIMP1 and FN1 expressions with clinicopathological characteristics of patients were analyzed by χ2 test, the correlation of TIMP1 and FN1 expressions with E-cad expression was analyzed by Spearman method, and the correlation of TIMP1 and FN1 expressions with survival was analyzed by Kaplan-Meier method. Results:The positive rates of TIMP1 and FN1 in PABC tissues were 72.7% (40/55) and 58.2% (32/55), and 25.5% (14/55) and 18.2% (10/55) in paracancerous tissues, and the differences were statistically significant ( χ2 values were 24.59 and 18.64, both P < 0.001). The results of Western blotting showed that the relative expressions of TIMP1 and FN1 proteins in the fresh cancer tissues of 10 PABC patients was higher than those in the corresponding paracancerous tissues (1.60±0.76 vs. 0.62±0.29, 1.31±0.62 vs. 0.44±0.15), and the differences were statistically significant ( t values were 5.92 and 4.86, both P < 0.001). The expressions of TIMP1 and FN1 in PABC tissues were correlated with estrogen receptor expression, Ki-67 positivity index, TNM stage and lymph node metastasis (all P < 0.05). The expressions of TIMP1 and FN1 were negatively correlated with expression of E-cad in PABC ( r values were -0.471 and -0.432, both P < 0.001). Five cases were lost to follow-up, and the remaining 50 cases had a median follow-up time of 43 months (12-90 months). Among the 50 cases, 36 cases were TMP1-positive and 29 cases were FN1-positive. The overall survival of TIMP1-negative group and FN1-negative group were better than those of the corresponding positive group ( χ2 values were 4.49 and 6.06, both P < 0.05); the median overall survival time of TIMP1-positive group and FN1-positive group were 51 months (95% CI 37-65 months) and 43 months (95% CI 32-53 months), while that of TIMP1-negative group and FN1-negative group were 89 months (95% CI 84-93 months) and 87 months (95% CI 85-92 months). Conclusions:TIMP1 and FN1 expressions are elevated in PABC tissues and negatively correlated with E-cad expression, TIMP1 and FN1 may be involved in PABC invasion through epithelial-mesenchymal transition and affect the prognosis of patients.

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.