Objective To compare the efficacy and safety between hypofractionated radiotherapy(HyRt)and conventional radiotherapy after breast-conserving surgery.Methods This study was a single-center,prospective,randomized controlled study.Eighty-three patients with pTis-T2N0M0 breast cancer admitted to Tangshan People's Hospital from May 2017 to May 2019 were included.The patients received breast-conserving surgery+sentinel lymph node biopsy(SLNB).After surgery,they were treated with intensity modulated radiation therapy(IMRT).According to random table method,patients were divided into HyRt group(n=41)and conventional radiotherapy group(n=42).The dose of organs at risk,treatment efficacy,treatment failure modes,and radiotherapy related adverse reactions were analyzed in the two groups.The radiotherapy-related adverse reactions were evaluated according to NCI CTC AE Version 3.0,including radiation dermatitis,radiation pneumonia,breast/skin fibrosis,pulmonary fibrosis,etc.Results Eighty-three patients with breast cancer were included,with a median age of 44(26-67)years.There was no statistically significant difference in clinical parameters such as age(P=0.443),TNM stage(P=0.335),molecular typing(P=0.333),degree of differentiation(P=0.617),and pathological type(P=0.127)between the two groups of patients.Compared with conventional radiotherapy group,the V5(25.6％vs.33.8％,P=0.015),V20(13.3％vs.17.2％,P=0.042),and the mean radiation dose(MLD;7.4 Gy vs.10.4 Gy,P=0.020)of the affected lung of HyRt group significantly decreased.Only 3 patients in this study experienced distant metastasis,and no regional lymph node metastasis or local recurrence was observed.There was no significant difference in PFS rate at 2 years between HyRt group and conventional radiotherapy group(94.4％vs.85.2％,P=0.818).Compared with conventional radiotherapy group,the incidence of≥grade Ⅱ irradiation dermatitis in HyRt group was significantly reduced(2.4％vs.21.4％,P=0.015).There was no difference in the incidence of grade Ⅰ breast/skin fibrosis(19.5％vs.14.3％,P=0.570)between the two groups,and no grade Ⅲ radiotherapy-related side effects were observed in the two groups.Conclusions Compared with conventional radiotherapy with simultaneously integrated boosting-intensity modulated radiotherapy,the patients who received HyRt after breast-conserving surgery for early-stage breast cancer have good tolerance and low incidence of adverse reactions.HyRt can be used as the first option of radiation therapy.

ObjectiveTo investigate the effect of myosin heavy chain 7 gene-derived miRNA-208b-3p on the fibrotic phenotype of cardiac fibroblasts. MethodsmiRNA chip array was performed to detect the dysregulated miRNAs in the myocardium of diabetic db/db mice and db/m control mice. Neonatal mouse ventricular cardiomyocytes （NMVCs） and cardiac fibroblasts （CFs） were isolated from C57BL/6 mice and cultured. Real-time quantitative PCR （RT-qPCR） was conducted to determine the expression of miR-208b-3p in mouse CFs and NMVCs subjected to angiotensinⅡ（AngⅡ） and high glucose plus glucose oxidase （G/Go） treatment， respectively. Cell counting kit 8（CCk8） assay， flow cytometry and determination of fibrosis-related protein， including COL1A1， COL3A1and α-SMA， were performed in mCFs transfected with miR-208b-3p. Dual luciferase reporter assay was performed to confirm the interaction between miR-208b-3p and the 3'-UTR of metal response element binding transcription factor 2 （Mtf2） and progesterone receptor membrane component 1（Pgrmc1）， respectively. The expressions of Mtf2 and Pgrmc1 at the mRNA and protein levels in mCFs after miR-208b-3p mimic transfection were determined using RT-qPCR and Western blot assay， respectively. The small interfering RNA （siRNA） was used to inhibit Mtf2 and Pgrmc1 expression in mCFs， and the effects of Mtf2 siRNA， Pgrmc1 siRNA and miR-208b-3p on fibrosis-related protein expression in mCFs were investigated. ResultsResults of miRNA chip array and RT-qPCR assay showed that miR-208b-3p was up-regulated in the myocardium of the diabetic db/db mice. miR-208b precursor and the host gene of Myh7 were consistently increased in db/db mice. miR-208b-3p and Myh7 mRNA were expressed in mCFs and NMVCs， but the levels of miR-208b-3p and Myh7 mRNA in NMVCs were much higher than those in mCFs. miR-208b-3p was up-regulated in mCFs and NMVCs subjected to Ang Ⅱ and G/Go treatment， respectively. miR-208b-3p could significantly enhance fibrosis-related protein， including COL1A1， COL3A1 and α-SMA， in mCFs， without affecting the proliferation activity and cell cycle distribution of mCFs. Dual luciferase reporter assay revealed the interactions of miR-208b-3p with the 3'-UTR of Mtf2 and Pgrmc1. The results of RT-qPCR and Western blotting confirmed that miR-208b-3p inhibited Mtf2 and Pgrmc1 expression at the post- transcriptional level. Transfection with miR-208b-3p mimic， Mtf2 siRNA and Pgrmc1 siRNA could consistently enhance the fibrosis-related protein expression in the cardiac fibroblasts. ConclusionsmiR-208b-3p enhances fibrosis-related gene expression by targeting Mtf2 and Pgrmc1in mCFs.

Objective:To examine the ultrasound images, clinical features, intraoperative conditions, and pathological features of ovarian clear cell carcinoma(OCCC)during perimenopause, in order to improve the early diagnosis of OCCC via ultrasound examination.Methods:A retrospective analysis of 29 patients, aged 42-72(56.8±7.4)years, who were surgically treated and pathologically diagnosed with OCCC at our hospital between 1 September 2015 and 31 December 2022, including 10 in the non-menopausal phase, 3(10.3%)in early menopausal transition, 7(24.1%)in late menopausal transition, and 19(65.5%)in the post-menopausal phase.The number of pregnancies(1.86±1.04)and the number of births(0.97±0.56)were also recorded.Results:In 29 cases, the masses contained solid components, and the ultrasound manifestations were as follows: (1)single-compartment cystic masses(solid components accounted for <50% of the total volume)were found in 11 cases, with clear borders, regular morphology, ground-glass echoes inside the cystic cavity, multiple solid protrusions inside the cystic cavity, and blood flow signals inside the solid components on color Doppler flow imaging(CDFI); (2)multi-compartment cystic masses(solid components accounted for <50% of the total volume)occurred in 8 cases, with largely clear borders, ground-glass echoes inside the cystic cavity, multiple solid protrusions inside the cavity, thick walls where the protrusions were attached, varying thickness of walls separating the cystic cavities, and blood flow signals inside the solid components, walls where there were solid attachments and thicker parts of the separating walls on CDFI; (3)there were 7 cases with predominantly solid cystic masses(the solid components accounted for >50% of the total volume), unclear borders, poor translucency, irregular morphology of the solid components, uneven internal echoes, and blood flow signals in the solid component on CDFI; (4)solid masses(the solid components accounted for >95%of the total volume)were seen in 3 cases with unclear borders, irregular morphology, uneven internal echoes, and a small number of cystic cavities(cystic portion <5%), with poor translucency in the cystic cavities and blood flow signals in the solid components on CDFI.Intraoperative exploration of ascites was performed in 17 cases, and adhesion between the mass and surrounding organs was found in 27 cases.Postoperative pathological results revealed 26 cases with high grade tumors and 3 cases with intermediate grade tumors.There were 3 cases with bilateral OCCC, 13 with left side OCCC and 13 with right side OCCC.According to the FIGO pathological staging system, 12 cases were in stage Ⅰ, 10 in stage Ⅱ, 5 in stage Ⅲ and 2 in stage Ⅳ.Comparison of different pathological stages(early stages Ⅰ and Ⅱ versus late stages Ⅲ and Ⅳ)showed statistically significant differences in the ratio of pathological stages between patients with different ultrasonographic manifestations( χ2=11.163, P<0.05), and the results of two-by-two comparisons showed that OCCC patients with ultrasonographic manifestations of solid masses(solid component accounting for >95%of the total volume)were more often in the late stage at the time of onset, while OCCC patients with a high number of cystic components within the lesions were more likely to be in the early stage at the time of onset.OCCC patients with more cystic components in the lesions tended to have an earlier onset and a better prognosis. Conclusions:When ultrasound imaging shows primarily a single chamber cystic solid mass in a patient in the perimenopausal phase with an endometriosis history, together with signs of specialized examination and pelvic adhesion during transvaginal sonography, a diagnosis of OCCC should be suspected.It is of great significance to pay attention to transvaginal sonography examination, ultrasound image features and clinical symptoms in perimenopausal women for the early diagnosis of OCCC.

Objective: To investigate the expression of VISTA and PD-L1 in triple-negative breast cancer (TNBC) and to explore its relationship with clinicopathologic features and prognosis. Methods: Ninety TNBC patients who underwent surgical resections between 2016 to 2018 in Jiangsu Province Hospital were selected. The expression of VISTA and PD-L1 in both tumor cells and immune cells was evaluated by immunohistochemistry, and the relationship with clinicopathologic parameters and prognosis was analyzed. Results: VISTA was expressed in 17.8% (16/90) of the tumors. The expression of VISTA in tumor cells was related to a higher Ki-67 proliferation index (P=0.02) and higher number of tumor-infiltrating lymphocytes (TIL, P<0.01). VISTA was expressed in 71.1% (64/90) of the immune cells and the expression correlated with smaller tumor size (P=0.02), lower T stage (P=0.04), higher number of TIL (P<0.01), higher number of CD8⁺T cells (P=0.03) and higher Ki-67 proliferation index (P=0.02). PD-L1 was expressed in 17.8% (16/90) of the immune cells and the expression correlated with higher histologic grade (P=0.04), higher Ki-67 proliferation index (P=0.02) and higher number of TIL (P<0.01). VISTA expression was higher in immune cells within TNBC patients than PD-L1 (P<0.01). Among 90 TNBC patients, complete follow-up was obtained in 85 patients, 8 of whom had recurrences or metastasis after surgery, and two patients cases died of recurrences or metastasis. Conclusions: The expression rate of VISTA is higher than that of PD-L1 in TNBC. The expression of VISTA in immune cells predicts a lower T stage. VISTA may act as an effective immunotherapy target.
B7-H1 Antigen/metabolism* ; Humans ; Ki-67 Antigen ; Prognosis ; Recurrence ; Triple Negative Breast Neoplasms/surgery*

Objective:To examine the ultrasonographic and clinical features of post-menopausal struma ovarii(PMOS).Methods:Clinical presentations and transvaginal sonography(TVS)data of 7 PMOS patients diagnosed during surgery were retrospectively analyzed and compared with histopathological results.Results:The ages of 7 patients ranged from 52 to 77 years(60.1±8.0 years, median age: 59 years, natural menopause age: 49.9±1.8 years). Ultrasound imaging data showed all adnexal masses were unilateral(1 on the left side, 6 on the right side). The focal lesions were irregular, round or elliptic in shape, measuring 2.8-9.5 cm, with either clear or unclear margins.Two PMSO cases were diagnose as teratoma on ultrasound, showing mixed echogenic patterns, with echoless interior regions and poor sound transmission.Color doppler flow imaging found no blood flow signal inside and around the mixed echogenic areas.Five cases were misdiagnosed on ultrasound, with 2 as postmenopausal ovarian endometrial cyst and 3 as ovarian cystadenocarcinoma.All patients recovered well after surgery.By the end of the follow-up, no recurrence of struma ovarii was found in the 7 cases.Conclusions:PMSO is a rare monodermal teratoma, can be easily misdiagnosed and needs to be differentiated from postmenopausal ovarian endometrial cyst, mature teratoma, ovarian cystadenocarcinoma and other types of lesions.A mass >5 cm may exhibit characteristic ultrasonographic manifestations, including protruding thyroid nodules, cyst wall calcification, etc.A solid portion of the cystic mass with blood flow may suggest a diagnosis of struma ovarii.

Objective:Nivolumab is one of the most common programmed death 1 （PD-1） inhibitors used as an immune checkpoint inhibitor （ICI）. It brings significant therapeutic effects but often accompanied by serious drug toxicity. The pulmonary toxicities of nivolumab are not clear. This study aims to systematically explore the nivolumab-associated pulmonary toxicities and provide reference for clinical treatment. Methods:Data were extracted from US Food and Drug Administration （FDA） Adverse Event Reporting System （FAERS） database from January 1， 2016 to September 30， 2019. Two types of disproportionality analysis， information component （IC） and reporting odds ratio （ROR）， were applied in nivolumab-associated pulmonary adverse events （AEs） signal detection. Results:A total of 28 489 309 records were extracted from FAERS database and 8 181 records were associated with nivolumab. Analysis was conducted in 179 AEs and 86 signals were detected. Notably， potent signals were detected in radiation pneumonitis （IC₀₂₅： 3.99， ROR₀₂₅： 17.25）， pneumonitis （IC₀₂₅： 3.34， ROR₀₂₅： 10.64） and bronchial fistula （IC₀₂₅： 2.94， ROR₀₂₅： 8.78）. Nivolumab-associated pulmonary toxicities were more frequently reported in dyspnoea （IC₀₂₅： 0.50， ROR₀₂₅： 1.44）， pneumonia （IC₀₂₅： 0.08， ROR₀₂₅： 1.07） and pneumonitis （IC₀₂₅： 3.34， ROR₀₂₅： 10.64）. Results of IC and ROR methods were similar to each other. Most pulmonary toxicities were observed in patients with non-small cell lung cancer （N=3 711， 32.13%）， malignant melanoma （N=1 658， 14.36%） and renal cell carcinoma （N=731， 6.33%）. Conclusion:Significant pulmonary toxicities were detected in patients treated with nivolumab. Thus， it is highly important for clinicians to be vigilant about nivolumab-associated pulmonary AEs and be prepared to take immediate action for patient safety.