Application of quality control circle in the management of early ambulation after cesarean section: An observational study.

BACKGROUND: The quality control circle (QCC) model has achieved good results in clinical applications in many hospitals in China and has gained popularity. This study aims to explore the application of QCC activities on early ambulation after cesarean section. METHODS: A QCC management group was established following standardized methods and techniques. The theme of the group was identified as "to enhance the implementation rate of the patient early ambulation after the cesarean section" through a matrix graph. The early ambulation rates after surgery of patients who received cesarean section were compared before and after QCC managements. RESULTS: Our data suggested that the early ambulation rates after cesarean section increased from 37.5% to 81.25% after applying QCC management. The biggest factor influencing the ambulation activities 24 ±â€…4 hours after the surgery was patients and family members do not cooperate. In addition, outstanding improvements in terms of nurses' sense of responsibility and self-confidence, communication and teamwork capacity in the problem-solving process were observed after the establishment of QCC. CONCLUSION: The application of QCC management had not only increase the early ambulation rates after cesarean section but also improved the quality of nursery care in general.

Rapamycin protects mouse skin from ultraviolet B-induced photodamage by modulating Hspb2-mediated autophagy and apoptosis.

BACKGROUND: Continuous exposure to UVB is the main extrinsic cause of skin photodamage, which is associated with oxidative stress, DNA damage, apoptosis and degradation of collagen. Rapamycin, a mechanistic target inhibitor of rapamycin complex 1 (mTORC1), has been shown to play a crucial role anti-tumor and aging retardation, but its mechanism of action in UVB-induced photodamage still remains unknown. In this study, we investigated the role of rapamycin and Hspb2 (also known as Hsp27) in UVB-induced photodamage in mice. METHODS AND RESULTS: We constructed skin acute photodamage models on the ears of WT and Hspb2 KO mice, respectively, and administered rapamycin treatment. Histological results showed that knockout of the hspb2 exacerbated the skin damage, as evidenced by thickening of the epidermis, breakage and disruption of collagen fibers and reduction in their number, which is reversed by rapamycin treatment. In addition, hspb2 knockout promoted UVB-induced apoptosis and reduced autophagy levels, with a significant increase in p53 levels and Bax/Bcl-2 ratio, a reduction in LC3II/I ratio and an increase in p62 levels in the KO mice compared to those in WT mice after the same dose of UVB irradiation. Rapamycin was also found to inhibit collagen degradation induced by hspb2 knockdown through activation of the TGF-ß/Smad signaling pathway. CONCLUSIONS: Rapamycin can alleviate skin photodamage from Hspb2 knockout to some extent. It may be a potential therapeutic drug for skin photodamage. In this study, we investigated the role of rapamycin and Hspb2 in UVB-induced photodamage in mice. Histological results showed that knockout of the hspb2 exacerbated the skin damage, as evidenced by thickening of the epidermis, breakage and disruption of collagen fibers and reduction in their number, which is reversed by rapamycin treatment. In addition, hspb2 knockout promoted UVB-induced apoptosis and reduced autophagy levels. Rapamycin was also found to inhibit collagen degradation induced by hspb2 knockdown through activation of the TGF-ß/Smad signaling pathway. We conclude that rapamycin and Hspb2 exert a synergistic protective effect in skin photodamage.

Localization of Ectopic Hyperparathyroidism: Ultrasound Versus 99mTc-sestamibi, 4-Dimensional Computed Tomography, and 11C-choline Positron Emission Tomography/Computed Tomography.

OBJECTIVE: To investigate the usefulness of ultrasound (US) for the localization of ectopic hyperparathyroidism and compare it with 99mTc-sestamibi (99mTc-MIBI), 4-dimensional computed tomography (4D-CT), and 11C-choline positron emission tomography/ computed tomography (PET/CT). METHODS: Of the 527 patients with surgically confirmed primary hyperparathyroidism, 79 patients with ectopic hyperparathyroidism were enrolled. The diagnostic performance of US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT was calculated, and the factors affecting the sensitivity of US and 99mTc-MIBI were analyzed. RESULTS: Eighty-three ectopic parathyroid lesions were found in 79 patients. The sensitivity was 75.9%, 81.7%, 95.1%, 83.3%, and 100% for US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT, respectively. The difference in sensitivity among these different modalities did not achieve statistical significance (P > .05). The US sensitivity was significantly higher for ectopic lesions in the neck region than for those in the anterior mediastinum/chest wall (85.9% vs. 42.1%, P < .001). The 99mTc-MIBI and 4D-CT sensitivity was not significantly different between these two groups (84.1% vs. 94.6%, P = .193 and 81.3% vs. 85.7%, P = 1). The 11C-choline PET/CT sensitivity was 100% in both groups. CONCLUSIONS: US is a valuable tool for the localization of ectopic hyperparathyroidism, especially for ectopic lesions in the neck region.

The multiple reference range of mean uterine artery pulsatility index for natural and in vitro fertilization singletons during 11-14 gestational weeks.

Background: Ultrasonography of the uterine artery (UtA) in the first and second trimesters of pregnancy can assess uterine-placental blood perfusion and guide early clinical prevention. Establishing normal ranges of the UtA pulsatility index (UtA-PI) at 11-14 weeks of pregnancy is helpful for the early identification of high-risk pregnant women and improving the prognosis. This study aimed to establish a reference range of UtA-PI based on crown-rump length (CRL) for spontaneous and in vitro fertilization (IVF) singleton pregnancy during 11-14 weeks, respectively. Methods: A prospective study was performed at Peking Union Medical College Hospital. Healthy, low-risk women with a singleton pregnancy at 11-14 gestational weeks were consecutively recruited for this study from December 2017 to December 2020. All participants underwent routine prenatal ultrasound examination. The CRL of the fetus and the UtA-PI were measured in both uterine arteries, and average values were calculated. The LMS method was used to fit the percentile (P)5, P10, P25, P50, P75, P90, and P95 curves of the UtA-PI value of spontaneous and IVF singleton pregnancy with CRL changes, respectively. Results: A total of 1,962 pregnant women with normal fetuses were included in this study, including 1,792 pregnancies conceived naturally and 170 IVF fetuses. The UtA-PI reference range in the spontaneous pregnancy group was consistently higher than that in the IVF group during 11-14 weeks, and showed a statistically significant difference in UtA-PI for spontaneous and IVF pregnancies (P<0.001). According to the LMS method, each percentile curve of UtA-PI decreased with the increase of CRL in both the natural pregnancy group and the IVF group. The P95 range of UtA-PI for pregnant women with naturally conceived and IVF pregnancy was 2.74 to 2.11 and 2.50 to 1.94, respectively. The overall change of UtA-PI differentials of the two groups showed a downward trend and decreased slightly with the increase of CRL. Conclusions: This study provided a single-center, large sample of data and constructed a CRL-based reference value of UtA-PI for spontaneous and IVF singleton pregnancy, which provides a reliable basis for early UtA evaluation and early clinical decision-making during 11-14 gestational weeks.

Regioselective synthesis of 3-nitroindoles under non-acidic and non-metallic conditions.

An electrophilic substitution reaction, without acid and metal, of indole with ammonium tetramethylnitrate for accessing 3-nitroindole has been developed. In this protocol, trifluoroacetyl nitrate (CF3COONO2) was produced by metathesis of ammonium tetramethyl nitrate and trifluoroacetic anhydride at sub-room temperature. Trifluoroacetyl nitrate (CF3COONO2) is an electrophilic nitrating agent for a variety of indoles, aromatic and heterocyclic aromaticity. Meanwhile, this strategy could be applied to construct the skeleton structure of many kinds of bioactive molecules. Interestingly, 3-nitroindole can be further derivatived as a pyrrolo[2,3-b]indole.

[Evaluation of Extrathyroidal Extension of Papillary Thyroid Microcarcinoma With Three-Dimensional Tomographic Ultrasound Imaging].

Objective To evaluate extrathyroidal extension (ETE) in papillary thyroid microcarcinoma (PTMC) with three-dimensional tomographic ultrasound imaging (3D-TUI). Methods A total of 97 thyroid nodules of 79 patients with PTMC treated in PUMC Hospital from February 2016 to January 2018 were included in this study.Two ultrasound experts performed independent blinded assessment of the relationship between thyroid nodules and thyroid capsule by two-dimensional ultrasound (2D-US) and 3D-TUI.The results of 2D-US and 3D-TUI in evaluating ETE were compared with intraoperative findings and postoperative histological and pathological results. Results Among the 97 nodules,54 (55.7%) nodules had ETE.The diagnostic sensitivity (68.5% vs.37.0%;χ2=10.737,P=0.002),accuracy (74.5% vs.56.7%;χ2=6.686,P=0.015),and area under the receiver operating characteristic curve[0.761 (95%CI=0.677-0.845) vs.0.592 (95%CI=0.504-0.680);Z=3.500,P<0.001] of 3D-TUI were higher than those of 2D-US.However,3D-TUI and 2D-US showed no significant difference in the specificity (84.1% vs.81.4%;χ2=0.081,P=0.776),negative predictive value (67.9% vs.50.7%;χ2=3.645,P=0.066),or positive predictive value (84.1% vs.71.4%;χ2=1.663,P=0.240). Conclusion Compared with 2D-US,3D-TUI demonstrates increased diagnostic efficiency for ETE of PTMC.

Pancreatic ductal adenocarcinoma with synchronous and metachronous hepatic metastasis predicted by contrast-enhanced ultrasound.

Background: Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods: This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results: The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions: CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

miR-449a ameliorates acute rejection after liver transplantation via targeting procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 in macrophages.

Acute rejection (AR) is an important factor that leads to poor prognosis after liver transplantation (LT). Macrophage M1-polarization is an important mechanism in AR development. MicroRNAs play vital roles in disease regulation; however, their effects on macrophages and AR remain unclear. In this study, rat models of AR were established following LT, and macrophages and peripheral blood mononuclear cells were isolated from rats and humans, respectively. We found miR-449a expression to be significantly reduced in macrophages and peripheral blood mononuclear cells. Overexpression of miR-449a not only inhibited the M1-polarization of macrophages in vitro but also improved the AR of transplant in vivo. The mechanism involved inhibiting the noncanonical nuclear factor-kappaB (NF-κB) pathway. We identified procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 (PLOD1) as a target gene of miR-449a, which could reverse miR-449a's inhibition of macrophage M1-polarization, amelioration of AR, and inhibition of the NF-κB pathway. Overall, miR-449a inhibited the NF-κB pathway in macrophages through PLOD1 and also inhibited the M1-polarization of macrophages, thus attenuating AR after LT. In conclusion, miR-449a and PLOD1 may be new targets for the prevention and mitigation of AR.

Gail model and fifth edition of ultrasound BI-RADS help predict axillary lymph node metastasis in breast cancer-A multicenter prospective study.

RATIONALE AND OBJECTIVES: We aim to assess the performance of the Gail model and the fifth edition of ultrasound BI-RADS (Breast Imaging Reporting and Data System) in breast cancer for predicting axillary lymph node metastasis (ALNM). MATERIALS AND METHODS: We prospectively studied 958 female patients with breast cancer between 2018 and 2019 from 35 hospitals in China. Based on B-mode, color Doppler, and elastography, radiologists classified the degree of suspicion based on the fifth edition of BI-RADS. Individual breast cancer risk was assessed with the Gail model. The association between the US BI-RADS category and the Gail model in terms of ALNM was analyzed. RESULTS: We found that US BI-RADS category was significantly and independently associated with ALNM (P < 0.001). The sensitivity, specificity, and accuracy of BI-RADS category 5 for predicting ALNM were 63.6%, 71.6%, and 68.6%, respectively. Combining the Gail model with the BI-RADS category showed a significantly higher sensitivity than using the BI-RADS category alone (67.8% vs. 63.6%, P < 0.001). The diagnostic accuracy of the BI-RADS category combined with the Gail model was better than that of the Gail model alone (area under the curve: 0.71 vs. 0.50, P < 0.001). CONCLUSION: Based on the conventional ultrasound and elastography, the fifth edition of ultrasound BI-RADS category could be used to predict the ALNM of breast cancer. ALNM was likely to occur in patients with BI-RADS category 5. The Gail model could improve the diagnostic sensitivity of the US BI-RADS category for predicting ALNM in breast cancer.

CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription.

Epigenetic alterations have been functionally linked to ovarian cancer development and occurrence. The CXXC zinc finger protein 1 (CFP1) is an epigenetic regulator involved in DNA methylation and histone modification in mammalian cells. However, its role in ovarian cancer cells is unknown. Here, we show that CFP1 protein is highly expressed in human ovarian cancer tissues. Loss of CFP1 inhibited the growth of human ovarian cancer cells, promoted apoptosis, and increased senescence. CFP1 knockdown resulted in reduced levels of SETD1 (a CFP1 partner) and histone H3 trimethylation at the fourth lysine residue (H3K4me3). RNA-sequencing revealed that deletion of CFP1 resulted in mRNA reduction of bone marrow stromal cell antigen 2 (BST2). Bioinformatics analysis and chromatin immunoprecipitation showed that CFP1 binds to the promoter of BST2 and regulates its transcription directly. Overexpression of BST2 rescued the growth inhibitory effect of CFP1 loss. Furthermore, depletion of cullin-RING ubiquitin ligases 4 (CRL4) components ROC1 or CUL4A had significantly inhibited the expression of CFP1 and BST2 similar to MLN4924 treatment that blocked cullin neddylation and inactivated CRL4s. In conclusion, CFP1 promotes ovarian cancer cell proliferation and apoptosis by regulating the transcription of BST2, and the expression of CFP1 was affected by CRL4 ubiquitin ligase complex.

Evaluation of the diagnostic performance of the EFSUMB CEUS Pancreatic Applications guidelines (2017 version): a retrospective single-center analysis of 455 solid pancreatic masses.

OBJECTIVES: To explore the diagnostic performance of EFSUMB CEUS Pancreatic Applications guidelines (version 2017) before and after the addition of iso-enhancement and very fast/fast washout as supplementary diagnostic criteria for PDAC. METHODS: In this retrospective study, patients diagnosed with solid pancreatic lesions from January 2017 to December 2020 were evaluated. Pancreatic ductal adenocarcinoma (PDAC) is reported to show hypo-enhancement in all phases according to the EFSUMB guidelines. First, based on this definition, all lesions were categorized as PDAC and non-PDAC. Then, iso-enhancement and very fast/fast washout were added as supplementary diagnostic criteria, and all lesions were recategorized. The diagnostic performance was assessed in terms of the accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV). The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings. RESULTS: A total of 455 nodules in 450 patients (median age, 58.37 years; 250 men) were included. The diagnostic performance using the EFSUMB CEUS guidelines for PDAC had an ACC of 69.5%, SEN of 65.4%, SPE of 84%, PPV of 93.5%, NPV of 40.6%, and ROC of 0.747. After recategorization according to the supplementary diagnostic criteria, the diagnostic performance for PDAC had an ACC of 95.8%, SEN of 99.2%, SPE of 84%, PPV of 95.7%, NPV of 96.6%, and ROC of 0.916. CONCLUSION: The EFSUMB guidelines and recommendations for pancreatic lesions can effectively identify PDAC via hypo-enhancement on CEUS. However, the diagnostic performance may be further improved by the reclassification of PDAC lesions after adding iso-enhancement and very fast/fast washout mode. KEY POINTS: • In the EFSUMB guidelines, the only diagnostic criterion for PDAC is hypo-enhancement, to which iso-enhancement and very fast/fast washout mode were added in our research. • Using hypo-enhancement/iso-enhancement with very fast/fast washout patterns as the diagnostic criteria for PDAC for solid pancreatic masses on CEUS has high diagnostic accuracy. • The blood supply pattern of PDAC can provide important information, and CEUS has unique advantages in this respect due to its real-time dynamic attenuation ability.

HSP27 Protects Skin From Ultraviolet B -Induced Photodamage by Regulating Autophagy and Reactive Oxygen Species Production.

Ultraviolet (UV) irradiation has been well documented to be linked with almost all skin problems we know, and both dermis and epidermis may be affected to varying degrees by UV irradiation. Every time when exposed to sunlight without protection, our skin will step closer to photoaging, leading to irreversible consequences ultimately. Heat shock protein 27 (HSP27) is a vital protein involved in cell growth, autophagy, apoptosis, drug resistance, tumor genesis and metastasis. Evidence suggests that the organism is subjected to various internal and external environmental stresses (heat, oxidative stress, organic toxicants, etc.), and HSP27 with high expression has protective function. However, the expression of HSP27 in coping with UV irradiation have not been examined thoroughly. In this study, photodamage models were developed through different doses of UVB irradiation in human epidermal keratinocytes (HEKs) (30 mJ/cm2), human dermal fibroblasts (HDFs) (150 mJ/cm2) and mouse skin (2,700 mJ/cm2). HSP27 knockdown decreased cell viability and increased the incidence of UVB-induced reactive oxygen species (ROS) production. We got consistent results in vivo and vitro. Compared with that in the UVB group, the expression of LC3B was significantly lower, while the expression of p62 was significantly higher in the UVB + si-HSP27 group. It was also revealed that HSP27 knockdown reduced the expressions of some antioxidants, such as superoxide dismutase (SOD) and catalase (CAT), which accelerated UVB-induced ROS release. Moreover, histological results showed that epidermis was thickened and collagen fibers were disorganized in the UVB + si-HSP27 group. These findings have demonstrated that HSP27 might play a photoprotective role in the UVB-induced skin damage process by maintaining the normal autophagy and antioxidant level. It is implied that HSP27 could be a potential therapeutic target of photodamage. However, determination of the definitive mechanism requires further exploration.

Association Between Vascular Index Measured via Superb Microvascular Imaging and Molecular Subtype of Breast Cancer.

Background: To determine whether vascular index (VI; defined as the ratio of Doppler signal pixels to pixels in the total lesion) measured via superb microvascular imaging in breast cancer correlates with immunohistochemically defined subtype and is able to predict molecular subtypes. Methods: This prospective study involved 225 patients with 225 mass-type invasive breast cancers (mean size 2.6 ± 1.4 cm, range 0.4~5.9 cm) who underwent ultrasound and superb microvascular imaging (SMI) at Peking Union Medical College Hospital before breast surgery from December 2016 to June 2018. The correlations between primary tumor VI measured via SMI, clinicopathological findings, and molecular subtype were analyzed. The performance of VI for prediction of molecular subtypes in invasive breast cancer was investigated. Results: The median VI of the 225 tumors was 7.3% (4.2%~11.8%) (range 0%~54.4%). Among the subtypes of the 225 tumors, 41 (18.2%) were luminal A, 91 (40.4%) were luminal B human epidermal growth factor receptor-2 (HER-2)-negative, 26 (11.6%) were luminal B HER-2-positive, 17 (7.6%) were HER-2-positive, and 50 (22.2%) were triple-negative, and the corresponding median VI values were 5.9% (2.6%~11.6%) (range 0%~47.1%), 7.3 (4.4%~10.5%) (range 0%~29.5%), 6.3% (3.9%~11.3%) (range 0.6%~22.2%), 8.2% (4.9%~15.6%) (range 0.9%~54.4%), and 9.2% (5.1%~15.3%) (range 0.7%~32.9%), respectively. Estrogen receptor (ER) negativity, higher tumor grade, and higher Ki-67 index (≥20%) were significantly associated with a higher VI value. Tumor size, ER status, and Ki-67 index were shown to independently influence VI. A cutoff value of 4.1% yielded 79.9% sensitivity and 41.5% specificity with an area under the receiver operating characteristic curve (AUC) of 0.58 for predicting that a tumor was of the luminal A subtype. A cutoff value of 16.4% yielded 30.0% sensitivity and 90.3% specificity with an AUC of 0.60 for predicting a triple-negative subtype. Conclusions: VI, as a quantitative index obtained by SMI examination, could reflect histologic vascular changes in invasive breast cancer and was found to be higher in more biologically aggressive breast tumors. VI shows a certain degree of correlation with the molecular subtype of invasive breast cancer and plays a limited role in predicting the luminal A with high sensitivity and triple-negative subtype with high specificity.

[Research Progress of Targeted Ultrasound Contrast Agent BR55].

BR55 is an ultrasound contrast agent targeting vascular endothelial growth factor receptor 2,which can be used to detect tumor neovascularization and improve the diagnostic accuracy.Overseas researchers have used BR55 for human ultrasound molecular imaging,which showed good safety and tolerance.We reviewed the research progress on BR55 applied in the evaluation of tumor neovascularization from the composition,characteristics,animal experiments,and clinical studies of BR55.

PFKFB3 Regulates Chemoresistance, Metastasis and Stemness via IAP Proteins and the NF-κB Signaling Pathway in Ovarian Cancer.

Glycolysis has been reported to be critical for cancer stem cells (CSCs), which are associated with tumor chemoresistance, metastasis and recurrence. Thus, selectively targeting glycolytic enzymes may be a potential therapy for ovarian cancer. 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), the main source of fructose-2,6-bisphosphate, controls the first committed step in glycolysis. We investigate the clinical significance and roles of PFKFB3 in ovarian cancer using in vitro and in vivo experiments. We demonstrate that PFKFB3 is widely overexpressed in ovarian cancer and correlates with advanced stage/grade and poor outcomes. Significant up-regulation of PFKFB3 was found in ascites and metastatic foci, as well as CSC-enriched tumorspheres and ALDH+CD44+ cells. 3PO, a PFKFB3 inhibitor, reduced lactate level and sensitized A2780CP cells to cisplatin treatment, along with the modulation of inhibitors of apoptosis proteins (c-IAP1, c-IAP2 and survivin) and an immune modulator CD70. Blockade of PFKFB3 by siRNA approach in the CSC-enriched subset led to decreases in glycolysis and CSC properties, and activation of the NF-κB cascade. PFK158, another potent inhibitor of PFKFB3, impaired the stemness of ALDH+CD44+ cells in vitro and in vivo, whereas ectopic expression of PFKFB3 had the opposite results. Overall, PFKFB3 was found to mediate metabolic reprogramming, chemoresistance, metastasis and stemness in ovarian cancer, possibly via the modulation of inhibitors of apoptosis proteins and the NF-κB signaling pathway; thus, suggesting that PFKFB3 may be a potential therapeutic target for ovarian cancer.

The Utility of the Fifth Edition of the BI-RADS Ultrasound Lexicon in Category 4 Breast Lesions: A Prospective Multicenter Study in China.

RATIONALE AND OBJECTIVES: The objective of this study was to evaluate the utility of the fifth edition of the Breast Imaging-Reporting and Data System (BI-RADS) in clinical breast radiology by using prospective multicenter real-time analyses of ultrasound (US) images. MATERIALS AND METHODS: We prospectively studied 2049 female patients (age range, 19-86 years; mean age 46.88 years) with BI-RADS category 4 breast masses in 32 tertiary hospitals. All the patients underwent B-mode, color Doppler US, and US elastography examination. US features of the mass and associated features were described and categorized according to the fifth edition of the BI-RADS US lexicon. The pathological results were used as the reference standard. The positive predictive values (PPVs) of subcategories 4a-4c were calculated. RESULTS: A total of 2094 masses were obtained, including 1124 benign masses (54.9%) and 925 malignant masses (45.1%). For BI-RADS US features of mass shape, orientation, margin, posterior features, calcifications, architectural distortion, edema, skin changes, vascularity, and elasticity assessment were significantly different for benign and malignant masses (p< 0.05). Typical signs of malignancy were irregular shape (PPV, 57.2%), spiculated margin (PPV, 83.7%), nonparallel orientation (PPV, 63.9%), and combined pattern of posterior features (PPV, 60.6%). For the changed or newly added US features, the PPVs for intraductal calcifications were 80%, 56.4% for internal vascularity, and 80% for a hard pattern on elastography. The associated features such as architectural distortion (PPV, 89.3%), edema (PPV, 69.2%), and skin changes (PPV, 76.2%) displayed high predictive value for malignancy. The rate of malignant was 7.4% (72/975) in category 4a, 61.4% (283/461) in category 4b, and 93.0% (570/613) in category 4c. The PPV for category 4b was higher than the likelihood ranges specified in BI-RADS and the PPVs for categories 4a and 4c were within the acceptable performance ranges specified in the fifth edition of BI-RADS in our study. CONCLUSION: Not only the US features of the breast mass, but also associated features, including vascularity and elasticity assessment, have become an indispensable part of the fifth edition of BI-RADS US lexicon to distinguish benign and malignant breast lesions. The subdivision of category 4 lesions into categories 4a, 4b, and 4c for US findings is helpful for further assessment of the likelihood of malignancy of breast lesions.

Gail Model Improves the Diagnostic Performance of the Fifth Edition of Ultrasound BI-RADS for Predicting Breast Cancer: A Multicenter Prospective Study.

RATIONALE AND OBJECTIVES: The sonographic appearance of benign and malignant breast nodules overlaps to some extent, and we aimed to assess the performance of the Gail model as an adjunctive tool to ultrasound (US) Breast Imaging Reporting and Data System (BI-RADS) for predicting the malignancy of nodules. MATERIALS AND METHODS: From 2018 to 2019, 2607 patients were prospectively enrolled by 35 health care facilities. An individual breast cancer risk was assessed by the Gail model. Based on B-mode US, color Doppler, and elastography, all nodules were evaluated according to the fifth edition of BI-RADS, and these nodules were all confirmed later by pathology. RESULTS: We demonstrated that the Gail model, age, tumor size, tumor shape, growth orientation, margin, contour, acoustic shadowing, microcalcification, presence of duct ectasia, presence of architectural distortion, color Doppler flow, BI-RADS, and elastography score were significantly related to breast cancer (all p < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the curve (AUC) for combining the Gail model with the BI-RADS category were 95.6%, 91.3%, 85.0%, 97.6%, 92.8%, and 0.98, respectively. Combining the Gail model with the BI-RADS showed better diagnostic efficiency than the BI-RADS and Gail model alone (AUC 0.98 vs 0.80, p < 0.001; AUC 0.98 vs 0.55, p < 0.001) and demonstrated a higher specificity than the BI-RADS (91.3% vs 59.4%, p < 0.001). CONCLUSION: The Gail model could be used to differentiate malignant and benign breast lesions. Combined with the BI-RADS category, the Gail model was adjunctive to US for predicting breast lesions for malignancy. For the diagnosis of malignancy, more attention should be paid to high-risk patients with breast lesions.

A Combination of Glutaminase Inhibitor 968 and PD-L1 Blockade Boosts the Immune Response against Ovarian Cancer.

Programmed cell death 1 ligand (PD-L1) blockade has been used therapeutically in the treatment of ovarian cancer, and potential combination treatment approaches are under investigation to improve the treatment response rate. The increased dependence on glutamine is widely observed in various type of tumors, including ovarian cancer. Kidney-type glutaminase (GLS), as one of the isotypes of glutaminase, is found to promote tumorigenesis. Here, we have demonstrated that the combined treatment with GLS inhibitor 968 and PD-L1 blockade enhances the immune response against ovarian cancer. Survival analysis using the Kaplan-Meier plotter dataset from ovarian cancer patients revealed that the expression level of GLS predicts poor survival and correlates with the immunosuppressive microenvironment of ovarian cancer. 968 inhibits the proliferation of ovarian cancer cells and enhances granzyme B secretion by CD8+ T cells as detected by XTT assay and flow cytometry, respectively. Furthermore, 968 enhances the apoptosis-inducing ability of CD8+ T cells toward cancer cells and improves the treatment effect of anti-PD-L1 in treating ovarian cancer as assessed by Annexin V apoptosis assay. In vivo studies demonstrated the prolonged overall survival upon combined treatment of 968 with anti-PD-L1 accompanied by increased granzyme B secretion by CD4+ and CD8+ T cells isolated from ovarian tumor xenografts. Additionally, 968 increases the infiltration of CD3+ T cells into tumors, possibly through enhancing the secretion of CXCL10 and CXCL11 by tumor cells. In conclusion, our findings provide a novel insight into ovarian cancer cells influence the immune system in the tumor microenvironment and highlight the potential clinical implication of combination of immune checkpoints with GLS inhibitor 968 in treating ovarian cancer.

Parathyroid disorder and concomitant thyroid cancer in patients with multiple endocrine neoplasia type 1: A retrospective cohort study.

ABSTRACT: This study aimed to determine the rates and characteristics of parathyroid disorder and thyroid cancer in patients with multiple endocrine neoplasia type 1 vs sporadic primary hyperparathyroidism (SPHP) undergoing parathyroidectomy.Patients with multiple endocrine neoplasia type 1-associated primary hyperparathyroidism (MPHP) or SPHP who underwent initial or reoperative parathyroid exploration from 1999 to 2019 were identified via a clinical database. The data for MPHP patients (n = 15) were compared to those of a selected 2:1 age- and sex-matched SPHP cohort (n = 30) who all underwent thyroidectomy for concurrent thyroid nodules.Compared with that of the SPHP group, the parathyroid hormone level of the MPHP group was much higher (470.67 ±â€Š490.74 pg/mL vs 217.77 ±â€Š165.60 pg/mL, P = .001). Multiglandular parathyroid disease (6/15 [40%] vs 3/30 [10%], P = .026) and more hyperplasia (7/15 [46.7%] vs 5/30 [16.7%], P = .039) were found in the MPHP group, and more parathyroid lesions presented as a round shape (long/short meridian < 2) by ultrasound (16/20 [80%] vs 8/31 [25.8%], P < .001). Regarding thyroid nodules, there was no difference in the rate of histologic thyroid cancer, but more thyroid cancer was found in the last 5 years among the MPHP cases (5/9 [55.6%] vs 3/18 [16.7%], P = .052).Multiglandular parathyroid disease and hyperplasia were more frequent in the MPHP cohort than in the SPHP cohort, and the parathyroid lesions usually presented with a round shape on ultrasonography. More concurrent thyroid cancer was found in MPHP than SPHP patients over the previous 5 years.