Objective:To investigate the accurate diagnosis and differential diagnosis of non-primary solid malignant tumors in breast needle core biopsy.Methods:Twenty-three cases of breast, axilla or neck lymph nodes pathologically diagnosed as non-primary solid malignant tumors were collected at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from January 2013 to March 2023. The differential diagnoses and diagnostic features were analyzed, based on combining clinical data, histology, and expression characteristics of biomarkers.Results:All patients were female, with age ranging from 29 to 75 years (average 56 years). The average time from the diagnosis of primary tumor to the current diagnosis was 21 months (0 to 204 months).The primary sites included the ovary (9 cases), the lung (5 cases), the gastrointestinal tract (4 cases), the pancreas, intrahepatic bile duct, thyroid gland, nasal cavity and forearm skin (1 case each). No carcinoma in situ was found in any of the cases. The morphological differences were significant among the tumors, but similar to the primary tumors. The tumors of neuroendocrine and female reproductive tract had great morphological and immunophenotypic overlaps with breast cancer. Metastatic lung cancer cells showed obvious atypia and tumor giant cells. The morphology and immunophenotype of metastatic serous carcinoma of female reproductive system might resemble invasive micropapillary carcinoma of the breast. Metastatic adenocarcinoma of the gastrointestinal tract often had features of mucous secretion. Metastatic neuroendocrine tumors were bland in appearance and morphologically similar to solid papillary carcinoma of breast, but negative for ER. TRPS1 was mostly negative (18/23) and variably positive in ovarian (4/9) and intrahepatic bile duct (1/1) tumors.Conclusions:The diagnosis of breast needle core biopsy specimen should be combined with clinical history, imaging study, and careful examination of histological features, such as presence of in situ component, morphological similarity between the primary and metastatic tumors, and using appropriate markers to differentiate the primary from metastatic tumors.

OBJECTIVE To evaluate the cost-effectiveness of denosumab and teriparatide in the treatment of postmenopausal osteoporosis in Chinese women， and provide reference for relevant decision-making. METHODS From the perspective of health system in China， Excel 2003 was used to establish Markov model， and cost-utility analysis was used to evaluate the cost- effectiveness of denosumab or teriparatide combined with Calcium carbonate D3 tablets in the treatment of postmenopausal osteoporosis in Chinese women. Pharmacotherapy effects were obtained with network meta-analysis， and cost and health utility value data were obtained from published literature. The model cycle was 1 year， and the simulation time limit was the patient’s lifetime. Univariate sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the effects of model parameter changes on the robustness of the results. Through scenario analysis， the cost-effectiveness of domestic drug cost used as drug cost of terlipatide group was discussed； the influence of residual effects of teriparatide on the results and the cost-effectiveness of sequential use of desumamab after terlipatide withdrawal were also discussed. RESULTS The effect of denosumab regimen was better than that of terlipatide regimen [13.24 quality-adjusted life years （QALYs） vs. 12.96 QALYs]， with lower cost （51 224.64 yuan vs. 167 102.67 yuan）， denosumab regimen was the absolutely superior regimen. The results of single factor sensitivity analysis showed that the cost and discount rate of Terlipatide injection had greater impact on the results. The results of probability sensitivity analysis showed that when three times of China’s per capita gross domestic product （GDP） in 2021 was used as the threshold of willingness to pay， the probability of cost-effectiveness of denosumab regimen was 93.5%. The results of scenario analysis showed that， whether the drug cost of terlipatide regimen which was replaced by domestic drugs， or the residual effect of terlipatide was considered， or desulmonab was used sequentially after two years of terlipide treatment， denosumab regimen was always the absolute advantage regimen. CONCLUSIONS Denosumab combined with Calcium carbonate D3 tablets is more cost-effective than teriparatide combined with Calcium carbonate D3 tablets in the treatment of postmenopausal osteoporosis in Chinese women.

BACKGROUND: Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated. METHODS: The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry. RESULTS: ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 . CONCLUSION ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.
Animals ; Mice ; Carcinoma in Situ ; Chalcones/pharmacology* ; Ferroptosis ; Gallbladder Neoplasms/genetics* ; Glutathione Disulfide ; Kelch-Like ECH-Associated Protein 1 ; Mice, Nude ; NF-E2-Related Factor 2/genetics* ; Reactive Oxygen Species ; Humans

Autophagy is a highly conservative cellular self-protective behavior dependent on lysosomes, and can be used as an important factor in promoting or preventing cancer, and its effect is related to the type and development of tumors. A full understanding of autophagy pathway is helpful to improve the diagnosis and treatment of tumors. Studies have shown that autophagy is closely related to the occurrence and development of oral tumors. Autophagy-related genes and signal pathways play a dual regulatory role on oral tumors. This article reviews the latest progress in the regulatory mechanism and therapeutic effect of autophagy on oral tumors.

Mycoplasma pneumoniae pneumonia (MPP) complicated with cerebral venous sinus thrombosis (CVST) is rare.We retrospectively analyzed the clinical data of two patients with refractory mycoplasma pneumoniae pneumonia (RMPP) complicated with CVST who were hospitalized in Xi′an children′s Hospital from December 2018 to April 2019, inquired the relevant literature, analyzed the clinical diagnosis and treatment characteristics, and discussed the diagnosis and treatment measures of RMPP complicated with CVST.Two cases were 6-year-old girls with fever and cough as the main symptoms.After physical examination, the respiratory sounds of the affected lung decreased, and the sounds of phlegm and dampness could be heard in both lungs.Mycoplasma pneumoniae (MP) antibody and RNA were positive.Chest CT showed lobar pneumonia with a large number of pleural effusion.The effect of macrolide antibiotics anti infection treatment was not good.Headache symptoms occurred during the course of the disease, and serum D-dimer increased significantly.Brain MRI showed CVST, including 1 case with lower extremity pain, and B-ultrasound showed right lower extremity arterial embolism.After anti infection, thrombectomy, anticoagulation and symptomatic treatment, 2 cases were discharged.When children with MPP, especially those with RMPP, have extracranial thrombosis and/or neurological symptoms, accompanied by elevated serum D-dimer, the possibility of CVST should be considered, and brain MRI examination should be performed in time to confirm and actively treat, which can reduce or avoid the occurrence of sequelae.Thrombosis may be related to excessive inflammatory reaction and vascular endothelial injury caused by MP infection.

Objective To observe the incidence,clinical characteristics,related factors,adverse events during hospitalization and short-term prognosis of postprandial hypotension (PPH) in elderly patients with coronary heart disease.Methods One hundred and sixty-eight elderly patients with coronary heart disease hospitalized in the Department of Cardiology,Second Hospital of Hebei Medical University from January 2014 to January 2015 were selected as the research subjects.They were monitored by 24 h ambulatory blood pressure monitoring.According to the diagnostic criteria of PPH,they were divided into postprandial hypotension group (PPH group) 34 cases and non-postprandial hypotension group (NPPH group) 134 cases.The clinical characteristics,risk factors related to PPH,occurrence of adverse events and prognosis of all-cause death,cardiovascular and cerebrovascular adverse events were compared between the two groups.Results Among 168 elderly patients with coronary heart disease,thirty-four patients had PPH,and the incidence rate was 20.2％ (34/168).The average systolic blood pressure before meals in PPH group was (139.8± 18.6) mmHg (1 mmHg =0.133 kPa).The proportion of taking calcium antagonists was 50.0％ (17/34) higher than that in NPPH group (127.4± 13.2) mmHg,27.6％ (37/134).The difference between the two groups was statistically significant (t =6.463,x2=6.232,P＜ 0.05).PPH was higher in breakfast and dinner than in lunch;the higher the basal systolic blood pressure level,the higher the incidence of PPH.Logistic regression analysis showed that the basal systolic blood pressure level and age were positively correlated with the occurrence of PPH (r =0.301,r =0.208,P＜ 0.05).Follow-up for 26 months showed that the incidence of all-cause death and cerebrovascular events in PPH group was higher than that in NPPH group (x2 =5.800,11.560,P＜ 0.05).Conclusion The incidence of PPH in elderly patients with coronary heart disease during hospitalization is 20.2％.Breakfast and dinner at three meals are prone to PPH.Older age and high systolic blood pressure level will increase the incidence of PPH.PPH will increase the incidence of mid-term all-cause death and cerebrovascular events.

Objective To investigate the diagnostic value of serum human epididymis protein 4 (HE4) ,carbohydrate antigen 125 (CA125) ,carbohydrate antigen antigen (CA199) ,carbohydrate antigen 153 (CA153) and alpha fetoprotein (AFP) in the early di-agnosis of ovarian cancer .Methods From February 2014 to October 2016 ,117 patients with ovarian cancers who were treated in this hospital were selected ,including 69 cases of ovarian cancer and 48 cases of benign ovarian lesions ,and 70 healthy volunteers were selected as control group .The serum levels of HE4 ,CA125 ,CA199 ,CA153 and AFP were measured in all subjects . Results The positive rates of HE4 ,CA125 ,CA199 ,CA153 and AFP in the ovarian cancer group were 59 .42% ,68 .12% ,33 .33% , 46 .38% and 39 .13% ,respectively ,which were significantly higher than those in the benign ovarian lesion group and the control group (P<0 .05) .The sensitivity of CA125 in the diagnosis of ovarian cancer was 68 .11% ,the specificity was 88 .98% ,the nega-tive predictive value was 78 .33% ,the positive predictive value was 82 .68% ,Youden index was 0 .571 .The diagnostic efficiency was better than that of other tumor markers .Pathological examination revealed 34 cases of serous adenocarcinoma ,18 cases of mucinous adenocarcinoma and 17 cases of endometrioid carcinoma in 69 cases of ovarian cancer .The positive rate of serous adenocarcinoma CA125 was 85 .29% ,significantly higher than mucinous carcinoma and endometrioid carcinoma (χ2 =9 .398 ,P<0 .05) .Conclusion CA125 has a good application value in the early diagnosis of ovarian cancer ,the positive rate is higher in serous adenocarcinoma .

Objective To explore the value of integrin αvβ3 micro positron emission tomography (microPET)/CT imaging with 68Ga-DOTA-RGD2 in diagnosis of breast cancer osteolytic bone metastases.Methods MDA-MB-231 was injected in left ventricle of hairless mice at the density of 1.0×10 7/mL.Animal model with parathyroid hormone(PTH)-induced osteolysis in the calvarium was established.Animals were randomly divided into RGD group (n=10) and FDG group (n=10), and were detected by 68Ga-DOTA-RGD2microPET/CT and 18F-NaFmicroPET/CT respectively.Animals were sacrificed and bone lesions were collected for pathological examination.Results Bone radiotracer uptake ratio of osteolytie lesion to normal calvrium (O/N) was (4.18±0.570) by 68Ga-DOTA-RGD2, which was significantly higher than (1.24±0.28) in group FDG by 18F-NaFmicroPET/CT imaging (P<0.05).Conclusion 68Ga-DOTA-RGD2 integrin receptor αvβ3 imaging can effectively detect breast cancer bone metastases and locate osteolytic lesions.

Objective To explore the value of integrin αvβ3 micro positron emission tomography (microPET)/CT imaging with 68Ga-DOTA-RGD2 in diagnosis of breast cancer osteolytic bone metastases.Methods MDA-MB-231 was injected in left ventricle of hairless mice at the density of 1.0×10 7/mL.Animal model with parathyroid hormone(PTH)-induced osteolysis in the calvarium was established.Animals were randomly divided into RGD group (n=10) and FDG group (n=10), and were detected by 68Ga-DOTA-RGD2microPET/CT and 18F-NaFmicroPET/CT respectively.Animals were sacrificed and bone lesions were collected for pathological examination.Results Bone radiotracer uptake ratio of osteolytie lesion to normal calvrium (O/N) was (4.18±0.570) by 68Ga-DOTA-RGD2, which was significantly higher than (1.24±0.28) in group FDG by 18F-NaFmicroPET/CT imaging (P<0.05).Conclusion 68Ga-DOTA-RGD2 integrin receptor αvβ3 imaging can effectively detect breast cancer bone metastases and locate osteolytic lesions.

AIM:To study the role of amifostine on the formation of benzo [a]pyrene (BaP)-induced abdomi-nal aortic aneurysm ( AAA) in C57BL/6J mice and the underlying mechanism .METHODS: RAW246.7 mononuclear macrophage in vitro were divided into control group , DMSO group, BaP group, low dose (1 μmol/L) amfostine treated group, middle dose (5 μmol/L) amfostine treated group and high dose (25μmol/L) amfostine treated group .The influ-ence of BaP on the expression of matrix metalloproteinase (MMP)-9, MMP-12, TNF-α, NF-κB in the RAW246.7 mono-nuclear macrophages in vitro was determined by Western blot .Male C57BL/6J mice (8 months old) were divided into con-trol group, model group (AngII+BaP group), low dose (50 mg/kg) amfostine treated group and high dose (100 mg/kg) amfostine treated group.After 6 weeks, the abdominal aorta were isolated .The aortic tissues were subjected to HE and Masson staining.The vascular wall structure , infiltration of macrophage , the expression of MMP-9, MMP-12, TNF-α, NF-κB were evaluated by Western blot and immunochemistry staining .RESULTS:Amifostine attenuated BaP-induced expres-sion of TNF-α, MMP-9, MMP-12, NF-κB in the RAW246.7 mononuclear macrophages (P<0.05).The results of animal experiments showed that the incidence of AAA in high dose amifostine treated group were significantly lower than that in low dose amifostine treated group and model group (P<0.05).Immunohistochemistry staining observation showed that amifos-tine inhibited the aortic macrophage infiltration more obviously in high amifostine treated group compared with model group and low dose amifostine treated group (P<0.05).Compared with model group and low dose amifostine treated group , the MMP-9, MMP-12, TNF-αand NF-κB expression of abdominal aorta in high amifostine treated group was reduced signifi -cantly ( P<0.05 ) .CONCLUSION: Amifostine inhibits BaP-induced activation of macrophages , and also prevents the formation of abdominal aortic aneurysm in C 57BL/6J mice induced by BaP by inhibition of the NF-κB pathway, macro-phage infiltration and the expression of TNF-αand MMPs.