Objective To explore the associations between risk factors for cardiovascular disease and breast cancer. Methods A total of 300 patients with breast cancer and 300 with benign breast diseases diagnosed by postoperative pathology were included in the Department of Breast Surgery, Huangpu Branch of the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine from January 2023 to June 2023. The main cardiovascular risk factors in patients between the two groups were compared. Stratification was performed according to menstrual status, and the main cardiovascular risk factors in patients with different menstrual status between the two groups were compared. The logistic regression correlation analysis was used to analyze the risk factors related to cardiovascular disease for breast cancer. Results There were statistically significant differences in clinical data and laboratory indicators between the two groups (P＜0.01) . Multivariate logistic regression analysis showed that age (OR=1.03, P=0.029), triglyceride (TG; OR=1.94, P=0.025), C-reactive protein (CRP; OR=2.73, P＜0.001), D-dimer (OR=61.19, P＜0.001), and homocysteine (Hcy; OR=2.10, P＜0.001) were independently associated with breast cancer. The stratified analysis showed age, TG, CRP, D-dimer, and Hcy were independently associated with breast cancer in both premenopausal and postmenopausal patients (P＜0.05). Conclusions Among risk factors for cardiovascular disease, advanced age, increased TG, CRP, D-dimer, and Hcy might increase breast cancer risk, which are helpful of screening high-risk individuals for breast cancer.

Objective:This study aims to explore the impact of various clinical factors on the risk of polymyxin B induced DKI in patients.Methods:This is a single-center retrospective case-control study. A total of 139 patients receiving polymyxin B intravenous treatment in our hospital from January 1 to December 31, 2020 were collected. Baseline variables between polymyxin B induced DKI group and non-DKI group were compared using the Chi-square test or Fisher's exact test for categorical variables and the T-test or Wilcoxon rank sum test for continuous variables, as appropriate. Statistical analysis was performed using univariate and multivariate Logistic regression models, Logistic regression models, multivariate Logistic regression models, Kaplan Meier curve, as well as Log-Rank test.Results:Among a total of 139 patients receiving polymyxin B treatment, 49 cases have experienced DKI, 90 cases did not. The incidence of DKI was 35.25%. There was no statistical difference in general information of age, gender, and proportion of standard weight between the two groups. Among the related indexes of polycolistin B administration, the proportion of high daily dose [>25 000 U/(kg·d)] and the total dosage of medication in the DKI group were both significantly higher than that in the non-DKI group ( P< 0.05, respectively). Among the organ function indexes, there were significant differences in initial serum creatinine, blood urea nitrogen, uric acid, urinary occult blood and urinary specific gravity between DKI group and non-DKI group 48 hours before polymyxin B administration ( P< 0.05). Binary Logistic regression analysis suggested that daily dose and initial creatinine before medication were independent risk factors for DKI caused by polymyxin B ( P< 0.05). Kaplan-meier survival analysis showed that with the accumulation of Polymyxin B administration, the higher the daily dose of Polymyxin B was, the faster the DKI occurred (Log-Rank P= 0.0194). Conclusions:Using intravenous polymyxin B is associated with the risk of DKI, among which higher initial blood creatinine values and higher daily doses are independent risk factors for DKI.

Objective:To explore the clinical value of urine semi-quantitative colorimetry by sodium dithionite reduction method in the diagnosis and treatment of diquat poisoning.Methods:The data of 49 patients with acute diquat poisoning treated in the First Affiliated Hospital of Nanjing Medical University from December 3, 2020 to November 23, 2022 were retrospectively analyzed, the correlation between urine colorimetric results and plasma diquat concentration was observed, and the predictive value of urine colorimetric results for target organ damage and prognosis were evaluated.Results:There was a significant correlation between urine colorimetric results and plasma diquat concentration, the correlation coefficient was r=0.89, P <0.01. The cut-off value of urine colorimetry for the predicting the damage of gastrointestinal tract, liver, kidney, and central nervous system injury were 2.5, 3.5, 3.5, 5.5, respectively; in which the urine colorimetric results showed the highest sensitivity in predicting digestive tract injury [ AUC 0.93 (95% CI:0.89-1.00)]. The cut-off value of urine colorimetry for the prognosis of death was 4.5, the positive predictive value was 64.2%, and the negative predictive value was 95.2%. Conclusions:The urine semi-quantitative method can be used for rapid prediction of the plasma diquat concentration range on admission. The urine colorimetry results can also effectively predict the occurrence of organ injury and clinical outcome related to diquat poisoning, which provides evidence for the clinical diagnosis and therapy.

The standardized training system for physicians has been implemented for many years in China. Based on the current situation of neurosurgery specialist training and the sub-professional development, the study discusses the specific plan and direction of glioma sub-professional physicians training from the aspects of glioma sub-professional physicians training outline, training content, requirements of glioma sub-professional training base, training assessment methods and training management. It provided reference for the training of neurosurgical glioma professionals in China, so as to make glioma receive comprehensive and standardized treatment.

Purpose: Isocitrate dehydrogenase 1 (IDH1) mutations are the most common genetic abnormalities in low-grade gliomas and secondary glioblastomas. Glioma patients with these mutations had better clinical outcomes. However, the effect of IDH1 mutation on drug sensitivity is still under debate. Materials and Methods: IDH1-R132H mutant cells were established by lentivirus. IDH1-R132H protein expression was confirmed by western blot. The expression of ataxia telangiectasia mutated (ATM) signaling pathway and apoptosis-related proteins were detected by immunofluorescence and western blot. Temozolomide (TMZ) induced cell apoptosis was detected by flow cytometry. Tumor cell proliferation was detected by Cell Counting Kit-8. In vivo nude mice were used to confirm the in vitro roles of IDH1 mutation. Results: We established glioma cell lines that expressed IDH1-R132H mutation stably. We found that TMZ inhibited glioma cells proliferation more significantly in IDH1 mutant cells compared to wild type. The IC50 of TMZ in IDH1-R132H mutant group was less than half that of wild-type group (p < 0.01). TMZ significantly induced more DNA damage (quantification of γH2AX expression in IDH1 mutation vs. wild type, p < 0.05) and apoptosis (quantification of AnnexinV+propidium iodide–cells in IDH1 mutation versus wild type, p < 0.01) in IDH1 mutant gliomas compared to wild-type gliomas. The ATM-associated DNA repair signal was impaired in IDH1 mutant cells. Inhibiting the ATM/checkpoint kinase 2DNA repair pathway further sensitized IDH1 mutant glioma cells to chemotherapy. We found that IDH1 mutation significantly inhibited tumor growth in vivo (the tumor size was analyzed statistically, p < 0.05). Moreover, we confirmed that gliomas with IDH1 mutation were more sensitive to TMZ in vivo compared to wild type significantly and the results were consistent with the in vitro experiment. Conclusion These results provide evidence that combination of TMZ and ATM inhibitor enhances the antitumor effect in IDH1 mutant gliomas.

Purpose: Isocitrate dehydrogenase 1 (IDH1) mutations are the most common genetic abnormalities in low-grade gliomas and secondary glioblastomas. Glioma patients with these mutations had better clinical outcomes. However, the effect of IDH1 mutation on drug sensitivity is still under debate. Materials and Methods: IDH1-R132H mutant cells were established by lentivirus. IDH1-R132H protein expression was confirmed by western blot. The expression of ataxia telangiectasia mutated (ATM) signaling pathway and apoptosis-related proteins were detected by immunofluorescence and western blot. Temozolomide (TMZ) induced cell apoptosis was detected by flow cytometry. Tumor cell proliferation was detected by Cell Counting Kit-8. In vivo nude mice were used to confirm the in vitro roles of IDH1 mutation. Results: We established glioma cell lines that expressed IDH1-R132H mutation stably. We found that TMZ inhibited glioma cells proliferation more significantly in IDH1 mutant cells compared to wild type. The IC50 of TMZ in IDH1-R132H mutant group was less than half that of wild-type group (p < 0.01). TMZ significantly induced more DNA damage (quantification of γH2AX expression in IDH1 mutation vs. wild type, p < 0.05) and apoptosis (quantification of AnnexinV+propidium iodide–cells in IDH1 mutation versus wild type, p < 0.01) in IDH1 mutant gliomas compared to wild-type gliomas. The ATM-associated DNA repair signal was impaired in IDH1 mutant cells. Inhibiting the ATM/checkpoint kinase 2DNA repair pathway further sensitized IDH1 mutant glioma cells to chemotherapy. We found that IDH1 mutation significantly inhibited tumor growth in vivo (the tumor size was analyzed statistically, p < 0.05). Moreover, we confirmed that gliomas with IDH1 mutation were more sensitive to TMZ in vivo compared to wild type significantly and the results were consistent with the in vitro experiment. Conclusion These results provide evidence that combination of TMZ and ATM inhibitor enhances the antitumor effect in IDH1 mutant gliomas.

Objective:To produce the solid target nuclide 89Zr , and prepare the probe 89Zr-desferrioxamine (DFO)-Trastuzumab. Methods:The 89Y(p, n) 89Zr nuclear reaction was used for 89Zr production. 89Y target was irradiated by 20 μA proton in a medical cyclotron ( E=12.5 MeV) for about 1-2 h. 89Zr was purified from hydroxamate resin using 1 mol/L oxalic acid solution. The characteristic peak, radionuclide purity and radiochemical purity of 89Zr were determined by γ-ray spectroscopy. 89Zr-DFO-Trastuzumab probe was synthesized by the reaction of 89Zr-oxalate and DFO-Trastuzumab at room temperature, and the radiochemical purity was measured. Results:89Zr was prepared successfully for 11 times, and the production of 89Zr was 555-1 506 MBq, with production rate of (34.8±5.2) MBq·μA -1·h -1. After the purification (purification rate: 42%-87%), 227.2-991.6 MBq 89Zr was obtained, with the concentration of 1.0×10 6 MBq/L. The γ spectrum showed that the characteristic peak of 89Zr were 511 and 909 keV, and no impurities were found. The radionuclide purity and radiochemical purity were both close to 100%. 89Zr-DFO-Trastuzumab was successfully labeled with radiochemical purity more than 95%, and it was above 90% within 72 h in human serum albumin (HSA) solution. Conclusion:Through the self-designed target assembling, the solid target PET nuclide 89Zr with high quality and labeling are successfully achieved, which provides guarantee for the clinical application of the 89Zr drug.

Objective: To optimize the radiolabeling of prostate specific membrane antigen (PSMA)-targeted probe Al¹⁸F-PSMA-BCH (Beijing Cancer Hospital) and to evaluate its potential for clinical trial and translation. Methods: The mixture of PSMA-BCH, AlCl₃, potassium biphthalate and no-carrier loaded ¹⁸F^- was reacted at 110 ℃ for 15 min, then purified by Sep-Pak Light C18 column and filtered through 0.22 μm sterile filter to obtain Al¹⁸F-PSMA-BCH. The radiolabeled yield and radiochemical purity were determined. Al¹⁸F-PSMA-BCH PET/CT imaging was performed on 5 healthy volunteers (age: (68±7) years) for biodistribution and radiation dosimetry estimate and on 1 patient (65 years) with recurrent prostate cancer. Results: The non-decay-corrected radiochemical yield of Al¹⁸F-PSMA-BCH was (38.0±3.5)% with the radiochemical purity >99% and the specific activity of (16.4±4.4) MBq/nmol. Al¹⁸F-PSMA-BCH was stable in saline at room temperature. In healthy volunteers, radioactivity was mainly accumulated in the bladder, kidneys, lacrimal glands, parotid glands and submandibular glands, of which kidneys were the most critical organs with the dosimetry of (152.89±33.43) μGy/MBq, while bones showed lower uptake ((11.10±1.23) μGy/MBq) than most organs. The effective dose of whole body was (0.013 5 ±0.002 5) mSv/MBq. Multiple bone metastases were observed by Al¹⁸F-PSMA-BCH PET/CT imaging in a patient with recurrent prostate cancer. Conclusions Al¹⁸F-PSMA-BCH prepared with the pH controller of potassium biphthalate holds the potential for the diagnosis, staging and monitoring recurrence of prostate cancer.

Immunosuppressant targeting programmed death protein-1 and its ligand (PD-1/PD-L1) is a hot topic in solid tumor immunotherapy.Detection of PD-1/PD-L1 expression in solid tumor patients by molecular imaging can predict whether tumor patients can benefit from immunotherapy.Small molecular polypeptide inhibitors have the advantages of low molecular weight,fast diffusion in tumor microenvironment,uniform distribution and easy access to the deep part of solid tumor.Non-invasive,real-time and quantitative detection of PD-1/PD-L1 expression in tumor patients can be performed by radionuclide labeled small molecular polypeptide inhibitor molecular probe PET imaging.It is expected to provide new detection methods for patient screening,efficacy monitoring,treatment plan optimization and prognosis evaluation.

Objective To explore the role of σ1 receptor (σ1R) in the clinical prognosis of cervical cancer,and provide a theoretical basis for σ1R targeted molecular therapy through observing the inhibition of synthetic σ1R-specific ligand compounds on the growth of cervical cancer cells. Methods (1) Immunohistochemical or immunocytochemistry staining were respectively used to detect the expression and localization of σ1R protein.(2)The Cancer Genome Atlas (TCGA) data set was used to validate our results. (3)Two series of 4 novel σ1R ligand compounds were synthesized by altering the N-terminal substituents on the piperidine ring of the prezamicol analogue, named as 14a, 14e, 15c and 15f. Methyl thiazolyl-tetrazolium (MTT) assay was detect the anti-proliferative effect of the four compounds on HeLa and SiHa cells. Compound 14a with potent inhibitory activity and the highest specificity of σ1R was selected for further experiments. Scratch test was observed the migration effect of compound 14a on HeLa and SiHa cells. Flow cytometry was determined cell cycles and apoptosis. Results (1) Immunostaining of σ1R protein was located in the cytoplasm and nucleus of cervical epithelium. The expression of cervical squamous cell carcinoma (SCC) was significantly higher than those of high-grade squamous intraepithelial lesion (HSIL) or normal cervical tissues. There was no significant difference in the expression of σ1R between HSIL and normal cervical tissues. σ1R expression in cervical adenocarcinoma (AC) was higher than that in SCC (P=0.020). The nuclear expression rate of σ1R in AC (10/18) was higher than that of SCC (27.1%, 19/70; P=0.024). The median overall survival (MOS) of σ1R-positive SCC patients was lower than that of σ1R-negative patients [(45.8±3.1) vs (51.7±2.9) months, P=0.045]. MOS of the patients with σ1R nuclear positive SCC was lower than that of non-nuclear staining [(38.9±3.8) vs (48.7±2.1) months, P=0.022]. MOS of the patients with σ1R nuclear positive AC was lower than that of non-nuclear staining [(35.0± 6.3) vs (44.2±4.2) months, P=0.034]. (2) Analysis of TCGA data showed that σ1R expression of in SCC was correlated with age (P=0.005). σ1R expression in AC was significantly associated with advanced stage, lymphnode metastasis and vascular invasion (all P<0.05). MOS of AC patients with σ1R overexpression was significantly lower than that of the patients with low expression (P=0.034). There was no significant difference in the MOS of different expression of σ1R mRNA in SCC patients(P=0.930). (3) MTT assay showed that these four compounds could suppressed the growth of HeLa and SiHa cells in time- and dose-dependent manner. The growth inhibition rates of HeLa and SiHa cells at 48 hours treated by combination of different concentrations of nedaplatin (NDP) with compound 14a (6 μmol/L) were significantly higher than those treated by NDP alone. Compound 14a (30 μmol/L) significantly inhibited the migration (both P<0.01) and induced the apoptosis of HeLa or SiHa cells (both P<0.01). Conclusions σ1R is over-expressed in cervical cancer and HSIL. σ1R nuclear expression is an important marker of AC. σ1R over-expression, especially σ1R nuclear expression is associated with the poor prognosis of cervical cancer. Our study is mostly consistent with cervical cancer data of TCGA. These results suggest that the novel synthetic prezamicol analogues 14a for σ1R could inhibit the growth of cervical cancer cells and cell migration through inducing apoptosis and arresting cell cycle in G0/G1 period, enhance NDP-induced cytotoxicity.