Zoledronic acid (ZA), a nitrogen-containing bisphosphonate with established clinical utility in osteoporosis management, exhibits emerging antitumor potential in estrogen receptor-positive breast cancer. However, the molecular mechanisms underlying its nonapoptotic anticancer effects remain poorly characterized. This study revealed that ZA induced ferroptosis in ER+ breast cancer cells through dual suppression of cystine-glutamate antiporter SLC7A11 and glutathione peroxidase 4 (GPX4), key repressors of ferroptosis. Pharmacological inhibition of ferroptosis using Ferrostatin-1 significantly attenuated ZA-induced cytotoxicity, while combinatorial treatment with the GPX4 inhibitor RSL3 synergistically enhanced lipid peroxidation and cell death. Mechanistically, ZA activated the Hippo-YAP signaling pathway, promoting YAP phosphorylation, proteasomal degradation, and cytoplasmic retention, thereby silencing SLC7A11 and GPX4. We established a novel metabolic vulnerability in hormone-responsive malignancies.These findings position ZA as a bifunctional ferroptosis inducer in ER+ breast cancer, offering a promising strategy to overcome endocrine resistance.

A 36-year-old healthy male served as an allogeneic hematopoietic stem cell donor was given recombinant human granulocyte colony-stimulating factor injection (rhG-CSF) 300 μg by subcutaneous injection once daily for 5 consecutive days. On day 4 of stem cell mobilization, peripheral stem cell collection was performed and rhG-CSF 250 μg was given in addition. The donor experienced dry cough, dyspnea, and difficulty breathing on the next day. Chest CT scan showed diffuse patchy and nodular shadows in both lungs, and relevant tests excluded bacterial/viral infection of the lungs and heart failure. It was considered to be acute lung injury caused by rhG-CSF. After giving glucocorticoids and symptomatic treatments, the symptoms gradually subsided, and the peripheral blood stem cell collection was successful. In the continuing treatment of glucocorticoids, the symptoms of the donor were further improved, and chest CT scan showed marked improvement. At a 3 years of follow-up, the donor' work and life were normal, and no lung discomfort symptoms recurred.

A 36-year-old healthy male served as an allogeneic hematopoietic stem cell donor was given recombinant human granulocyte colony-stimulating factor injection (rhG-CSF) 300 μg by subcutaneous injection once daily for 5 consecutive days. On day 4 of stem cell mobilization, peripheral stem cell collection was performed and rhG-CSF 250 μg was given in addition. The donor experienced dry cough, dyspnea, and difficulty breathing on the next day. Chest CT scan showed diffuse patchy and nodular shadows in both lungs, and relevant tests excluded bacterial/viral infection of the lungs and heart failure. It was considered to be acute lung injury caused by rhG-CSF. After giving glucocorticoids and symptomatic treatments, the symptoms gradually subsided, and the peripheral blood stem cell collection was successful. In the continuing treatment of glucocorticoids, the symptoms of the donor were further improved, and chest CT scan showed marked improvement. At a 3 years of follow-up, the donor' work and life were normal, and no lung discomfort symptoms recurred.

Objective:To establish a simplified anatomical model with the selected rabbits widely distributed in China′s dry region as the reference species and compare the result of internal exposure dose coefficients based on the present mode and ERICA.Methods:A simplified anatomical model based on anatomy and geometry was established for rabbits. Combined with Monte Carlo program, the deposited energy of radionuclide particles in rabbit tissues/organs was obtained, and the internal and external exposure dose coefficient for rabbits was calculated following the empirical formula.Results:Simplified anatomy model-based dose coefficients were 129I 4.81 × 10 -6, 137Cs 4.34 × 10 -5, and 134Cs 3.81 × 10 -5(μGy·h -1)/(Bq·kg -1) for internal exposure and 129I 3.16 × 10 -7, 137Cs 2.39 × 10 -4 and 134Cs 6.22 × 10 -4(μGy·h -1)/(Bq· kg -1) for external exposure. respectively. ERICA-based dose coefficients were 129I 4.44 × 10 -5, 137Cs 1.94 × 10 -4 and 134Cs 2.34 × 10 -4(μGy·h -1)/(Bq·kg -1) for internal exposure and 129I 2.19 × 10 -6, 137Cs 2.52 × 10 -4 and 134Cs 6.95 × 10 -4(μGy·h -1)/(Bq·kg -1) for external exposure, respectively. Conclusions:The simplified anatomical model established is based on the measured data and focuses on the radiation doses to biological tissues/organs, and the calculated result based on the present model are closer to the actual situation, and can provide reference values for the reference biological evaluation of non-human species.

ObjectiveTo observe the effect of rapamycin on the proliferation and cell cycle of prostate cancer cell lines PC3,and to investigate the mechanism that it inhibits the growth and metastasis of prostate cancer cells.MethodsPC3 cells were cultured in vitro,and treated with different concentrations (10,25ng/ml) of cycle raparnycine.MTT was used to measure the change of proliferation of PC3 cells.Flow cytometry was used to measure the changes of cell cycle and apoptosis of PC3 cells.Nude mice were used to detect the effect of rapamycin on metastasis.ResultsThe proliferation of PC3 cells was significantly inhibited by rapamycin,and a time- and concentration-dependent relationship was shown,the inhibited rate was(42.23 ± 0.78 ) ％ after 36 h in the group of 25 ng/ml ( P ＜ 0.05 ).Flow cytometry analysis showed rapamycin significantly inhibited the cell cycle,prompted the apoptosis,and increased the number of cells in G0/G1 phase at 36 h with a rate of cell staying at Go/G1 [ (92.17 ± 0.69 ) ％ ] ( P ＜ 0.05 ).The weight of tumors in nude mice in the control group was significantly greater than that in RPM group[ (3.41± 0.28)g vs ( 1.19 ± 0.23 )g] ( P＜ 0.05 ),and metastatic sites of the lung and liver in the control group were significantly mote than the RPM group [ 100％ (7/7) vs 14.29％ ( 1/7 ) ] ( P ＜ 0.05 ).Conclusions Rapamycin significantly inhibits the proliferation and metastasis of osteosarcoma.The rapamycin-based regimen is valuable for clinical application.

ObjectiveReport an operation of off-pump occlusion of trans-thoracic minimal invasive surgery (OPOTTMIS) adopted on the therapy of 92 patients suffered with simple congenital heart diseases (CHD) of atrial septal defect ( ASD),ventricular septal defect ( VSD ) and patent ductus arteriosus (PDA) and summarize the experiences.Methods The clinical data of 92 CHD patients administrated with OPOTTMIS in our hospital during the time of July 2008 and July 2011 were analyzed retrospectively.Moreover,the relevant literatures were reviewed and the different kinds of treatments and their outcomes of CHD were compared.These patients were 3-56 years old and weighed 8.0-54.5 kg,with male and female 38 and 54 cases,including ASD 52 cases,VSD 26 cases and PDA 14 cases,respectively.Within the initial 3 months of postoperation,all the patients were followed up and managed to take the re-examination with electrocardiogram and echocardiogram one time for each month,and 3 months later,at least one time for every 3-6 months.Results91 cases were performed the OPTTMIS procedure successfully,1 child with sieve-like ASD transferred to open-heart surgery and 1 adult( 1.1％ ) PDA died on the second day after operation for the pulmonary hypertension crisis.4 cases appeared mild residual shunt including 2 of ASD,1 of VSD and 1 of PDA.2 cases showed Ⅱ stage atrial ventricular block ( AVB ) within ASD and VSD,respectively.Also,post-operation hemothorax happened to 1 case ASD and 1 case VSD for the active bleeding of cardiac puncture site and the exploration and hemostatic operation were performed.91 (98.9％) patients were performed the OPOTTMIS operation successfully,the total complications within 72 hours was 6.5％ (6/92),respectively.There were no heavy complications happened during peri-operation such as cardiac rupture,infective endocarditis,stroke,hemolytic and thrombus formation.90 patients outcomes of 3 months to 4 years follow-up with the ECG and UCG examination showed that there were no Ⅲ stage atrioventricular block,no obvious occluder shift and broken and no moderate cardiac valve regurgitation,no evident blood flow restriction of left ventricular outflow tract and descending aorta,only found mild residual shunt within 2 cases ( VSD and PDA each) and heart expansion compared to pre-operation within 2 PDA patients.However,all the patients'heart functions were in grade Ⅰ to grade Ⅱ according to NYHA standard.ConclusionOPOTTMIS is a safe,feasible and effective option on simple congenital heart diseases.

Objective To observe the hemostatic effect of emergent hemostasis patch (EHP). Methods The coagulation time was studied with tube method in vitro. Hemostasis was studied with femoral artery hemorrhage models of rats and dogs as well as rabbit hepatorrhexis model in vivo. Results The clotting time of EHP of high, medium and low concentrations was (4.9±1.3)min, (5.7±1.8)min and (5.8±1.3)min, respectively, which was significantly lower than that of control (14.4±1.6)min in vitro. In femoral hemorrhage models of rats and dogs, the duration and amount of bleeding in EHP of high, medium and low doses were significantly decreased compared with those in the PVF sponge group (P<0.01 or P<0.05). The results of rabbit hepatorrhexis experiment showed that EHP of three doses obviously decreased the hemostatic time and blood loss compared with PVF sponge group (P<0.01). Conclusion EHP can shorten coagulation time and bleeding time, and reduce bleeding amount.