Objective To predict the lymphovascular invasion(LVI)status of breast cancer patients based on digital breast tomo-synthesis(DBT)intratumoral and peritumoral radiomics nomogram.Methods A total of 192 breast cancer patients from 2 institu-tions were retrospectively selected,in which institution 1 was used for train(n=113)and test(n=49),while institution 2 was used for external validation(n=30).Radiomics features were extracted and selected based on intratumoral and peritumoral 1 mm regions from DBT images.Different machine learning algorithms were used to construct intratumoral,peritumoral,and combined intratumoral and peritumoral models,respectively.Patient clinical data were analyzed by both univariate and multivariate logistic regression analy-ses to identify independent risk factors for the clinical imaging model.The performance of the models was evaluated using the receiver operating characteristic(ROC)curve.The radiomics features with the optimal diagnostic performance and the selected clinical imaging features were combined to construct a comprehensive clinical-radiomics model,and a nomogram was drawn.Results The combined intratumoral and peritumoral model was the optimal radiomics model.Maximum tumor diameter[odds ratio(OR)=1.486,P=0.014],suspicious malignant calcifications(OR=2.898,P=0.015),and axillary lymph node(ALN)metastasis(OR=3.615,P<0.001)were independent risk factors for LVI positive.Furthermore,the area under the curve(AUC)of the comprehensive clinical-radiomics model in the training set,test set and external valida-tion set was 0.889,0.916,and 0.862,respectively,which was higher than those of the combined intratumoral and peritumoral model(0.858,0.849,0.844)and the clinical imaging model(0.743,0.759,0.732).Conclusion The predictive nomogram,derived from both radiomics and clinical imaging features,is relatively accurate in identifying future LVI occurrence in breast cancer,demonstra-ting its potential as an assistive tool for clinicians to devise individualized treatment regimes.

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective To predict the lymphovascular invasion(LVI)status of breast cancer patients based on digital breast tomo-synthesis(DBT)intratumoral and peritumoral radiomics nomogram.Methods A total of 192 breast cancer patients from 2 institu-tions were retrospectively selected,in which institution 1 was used for train(n=113)and test(n=49),while institution 2 was used for external validation(n=30).Radiomics features were extracted and selected based on intratumoral and peritumoral 1 mm regions from DBT images.Different machine learning algorithms were used to construct intratumoral,peritumoral,and combined intratumoral and peritumoral models,respectively.Patient clinical data were analyzed by both univariate and multivariate logistic regression analy-ses to identify independent risk factors for the clinical imaging model.The performance of the models was evaluated using the receiver operating characteristic(ROC)curve.The radiomics features with the optimal diagnostic performance and the selected clinical imaging features were combined to construct a comprehensive clinical-radiomics model,and a nomogram was drawn.Results The combined intratumoral and peritumoral model was the optimal radiomics model.Maximum tumor diameter[odds ratio(OR)=1.486,P=0.014],suspicious malignant calcifications(OR=2.898,P=0.015),and axillary lymph node(ALN)metastasis(OR=3.615,P<0.001)were independent risk factors for LVI positive.Furthermore,the area under the curve(AUC)of the comprehensive clinical-radiomics model in the training set,test set and external valida-tion set was 0.889,0.916,and 0.862,respectively,which was higher than those of the combined intratumoral and peritumoral model(0.858,0.849,0.844)and the clinical imaging model(0.743,0.759,0.732).Conclusion The predictive nomogram,derived from both radiomics and clinical imaging features,is relatively accurate in identifying future LVI occurrence in breast cancer,demonstra-ting its potential as an assistive tool for clinicians to devise individualized treatment regimes.

【Objective】 To reveal the integral in vivo polypharmacokinetics (PPK) similarity or difference between Jinyinhua (Lonicerae Japonicae Flos, LJF) and Shanyinhua (Lonicerae Flos, LF), and provide reference for their clinical application. 【Methods】 The PPK model and its total quantum statistical moment similarity (TQSMS) method were used to compare the integral PPK profiles of nine components with anti-inflammatory efficacy (rutin, caffeic acid, chlorogenic acid, cryptochlorogenic acid, dispsacoside B, macranthoidin B, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C) of LJF and LF. A total of 54 Specific Pathogen Free (SPF) grade Kunming (KM) mice were randomized into LJF group and LF group (n = 27), and each group was divided into nine subgroups (n = 3) according to different time points. Subsequently, mice model of p-xylene-induced ear edema was constructed by oral administration of LJF and LF. The concentrations of the nine anti-inflammatory components in plasma samples of the mice were determined by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). And the pharmacokinetics (PK) parameters of single component and the integral PPK parameters [total quantum statistical moment (TQSM) and TQSMS] of multiple components were calculated by Drug And Statistics (DAS) software and home-brew programs with Excel, respectively. 【Results】 There were significant differences in single-component PK parameters between LJF and LF (P < 0.05). Whereas, no significant differences were found in multi-component TQSM parameters, including total quantum zero moment (AUCT0-t, AUCT0-∞) and total quantum first moment (MRTT0-t, MRTT0-∞) for the total quanta (P > 0.05). Accordingly, single-component TQSMS varied from 0.220 4 to 0.968 9, and that for the total quanta was 0.828 4, suggesting no significant differences in the speed and extent of bioavailability between LJF and LF. Furthermore, in light of high TQSMS (0.828 4), the integral PPK profiles of the nine anti-inflammatory components of LJF and LF were similar under 90% confidence intervals. 【Conclusion】 The PPK model and its TQSMS method are appropriate and efficient to compare the similarity or difference of integral PPK profiles of multi-component herbal medicines. It is suggested in this research that LJF can be replaced with LF or vice versa for anti-inflammatory treatment.

Ganjiang (Zingiberis Rhizoma, ZR) and Jiangtan (Carbonized Zingiberis Rhizoma, CZR) have long been used in traditional Chinese medicine (TCM) with a rich history in the treatment of various ailments. While ZR and CZR obviously stem from the same botanical source, their attributes, chemical compositions, pharmacological behaviors, and clinical applications are different owing to variations in the extent of drying and processing they undergo. In this paper, data pertaining to ZR and CZR were retrieved from databases including China National Knowledge Infrastructure (CNKI), PubMed, Web of Science, and Google Scholar. These sources were scrutinized to elucidate the distinctions between ZR and CZR arising from carbonization processing in terms of their ethnopharmacology, quality control, chemical compositions, biological activities, pharmacological mechanisms, and clinical uses. In this study, a total of 56 chemical constituents were identified and isolated from ZR and CZR, which primarily encompassed volatile oils, gingerols, and diphenylheptane compounds. CZR's pharmacological effects include hemostatic, anti-oxidant, analgesic, antibacterial, anti-cancer, and other biological activities. ZR has pungent and warm properties. It is a Yang-supplementing herbal medicine for ailments exacerbated by cold or damp climatic influences. CZR is a product of ZR after undergoing high temperature, with diminished intensity of its pungent and warm attributes. This change leads to a more gradual treatment efficacy, renowned hemostatic effects and its ability to gently invigorate the spleen and effectively alleviate diarrhea. Currently, research on the pharmacological mechanism of CZR is mainly focused on the effects of CZR on coagulation and fibrinolysis. Although the healing effect of CZR has long been known, and some correlation has been found between the changing composition and the changing color of the decoctions, people still lack relatively clear processing mechanisms to reflect the characteristics and specific quality standards of the ingredients of CZR's hemostatic effect. This review provides a systematic summary on quality control, chemical composition, ethnopharmacology, and pharmacology of CZR, offering novel perspectives for advancing the exploration of additional carbonized herbal medicine and fostering their application in clinical settings

Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations.

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis and high mortality. In this study, we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine α-1,3-galactose epitopes (αGal) and endorphin extracellular domains (END) with dendritic cells (DCs) from healthy volunteers. END⁺/Gal⁺-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes (CTLs) and secretion of interferon-gamma (IFN-γ). CTLs targeted cells expressing αGal and END and tumor angiogenesis. The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice, indicating the high clinical potential of this new cell based vaccine.

ObjectiveTo explore the effect of Jinshui Xiangsheng prescription on the five-year clinical survival outcome of patients with advanced prostate cancer. MethodFrom May 1, 2014 to May 1, 2016, patients with advanced prostate cancer from Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine and the Urology Department of the Second Affiliated Hospital of Nanjing University of Chinese Medicine were collected and treated with Jinshui Xiangsheng prescription (155 cases in the observation group). According to age and Gleason score, the patients without Jinshui Xiangsheng prescription were matched in a ratio of 1∶1 (155 cases in the control group). The androgen resistance rate, survival rate, median survival time, and median progress free survival time in 1, 3, 5 years were observed. The prognostic factors of advanced prostate cancer were analyzed and screened out by Chi-square test, t test, Kaplan-Meier and Cox survival analysis. ResultThe androgen resistance rates in the observation group in 1， 3， 5 years were 9.0% （14/155）， 72.3% （112/155）， and 92.9% （144/155）， respectively， and those in the control group were 20.6% （32/155）， 87.7% （136/155）， and 97.4% （151/155）. The 1-year （χ²=8.271，P<0.01）and 3-year （χ²=11.613，P<0.01） androgen resistance rates in the observation group were significantly lower than those in the control group. The median survival time and median progress free survival time in the observation group were （26.35±9.01） months and （11.02±4.40） months， respectively， and in the control group were （22.31±9.21） months and （9.87±5.12） months， respectively. The median survival time and median progress free survival time in the observation group were significantly longer than those in the control group （P<0.05， P<0.01）. The cumulative survival rates in 1， 3， 5 years in the observation group were 96.1% （149/155）， 80.6% （125/155）， and 39.4% （61/155）， respectively， and those in the control group were 94.2% （146/155）， 60.0% （93/155）， and 22.6% （35/155）， respectively. The 3-year （χ²=15.828，P<0.01） and 5-year （χ²=10.201，P<0.01） cumulative survival rates in the observation group were significantly higher than those in the control group. The monofactor analysis showed that the prognostic factors involved in Gleason score， initial prostate specific antigen （PSA）， tumor location， tumor stage， castration regimen， radiotherapy， chemotherapy， complete androgen blockade （CAB）， and Jinshui Xiangsheng prescription （P<0.05， P<0.01）. The multivariate analysis showed that initial PSA， tumor location， and tumor stage were the risk factors affecting the survival time of patients with advanced prostate cancer， whereas Jinshui Xiangsheng prescription， castration regimen， chemotherapy， radiotherapy， and CAB were the independent protective factors affecting the prognosis of advanced prostate cancer. ConclusionJinshui Xiangsheng prescription has a protective effect on the survival of patients with advanced prostate cancer， which reduces the androgen resistance rate and death risk of advanced prostate cancer， thus benefiting the survival of patients. Therefore， it deserves further promotion.

Objective:To investigate the short-term clinical efficacy of laparo-gastroscopic esophagectomy (LGE).Methods:The retrospective and descriptive study was conducted. The clini-copathological data of 11 patients with esophageal cancer who underwent LGE in the Zhongshan Hospital of Fudan University from June 2020 to October 2021 were collected. There were 8 males and 3 females, aged (68±4)years. Sorted by operation time, the sentinel lymph nodes navigation (SLN) was performed since the sixth patient in the cohort, and abdominal surgery and neck surgery were performed simultaneously to complete LGE. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted using outpatient examination or telephone interview to detect death of patients during postoperative 30 days. Patients were followed up during postoperative 30 days. Measurement data with normal distribution were represented as Mean± SD, and count data were described as absolute numbers. Results:(1) Surgical situations. Of the 11 patients, 5 cases received SLN with satisfactory visualization, 6 cases did not receive SLN, 1 case terminated the operation as sentinel lymph nodes biopsy showing positive results and the rest of 10 cases completed LGE successfully without conversion to thoracotomy. The operation time and tumor diameter of the 10 patients completing LGE was (204±27)minutes and (2.5±1.0)cm, respec-tively. (2) Postoperative situations. Of the 10 patients completing LGE, 2 cases had pulmonary complications after surgery and recovered well with symptomatic treatment, and none of patient had anastomotic leakage or other serious complication. Results of postoperative histopathological examination showed squamous cell carcinoma in the 10 patients completing LGE. Nine patients were classified as T1b?3N0M0 stage and 1 patient was classified as T1bN1M0 stage. Ten patients completing LGE had R 0 resection and the number of lymph nodes dissected was 14±4. There were 3 cases with nerve bundle invasion, 2 cases with vascular invasion and 5 cases without nerve bundle and vascular invasion. The postoperative treatment time at intensive care unit and duration of hospital stay of the 10 patients completing LGE were (4.0±2.4)days and (7.2±1.5)days. (3) Follow-up. The 10 patients completing LGE were followed up and none of them died during the postoperative 30 days. Conclusions:LGE is safe and feasible. Combined with SLN can guarantee the oncology effect of surgery.