Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

OBJECTIVES: To investigate the association between methylation levels of tumor suppressing subtransferable candidate 1 (TSSC1) and melanophilin (MLPH) genes in peripheral blood and coronary heart disease (CHD) in Chinese population. METHODS: This case-control study was conducted in 86 CHD patients and 95 healthy individuals, whose methylation levels of TSSC1 and MLPH genes in peripheral blood were determined using mass spectrometry. Mann-Whitney U test was used to compare the methylation levels in different subgroups. The correlation of TSSC1 and MLPH gene methylation levels with age and gender were evaluated using Spearman correlation coefficient and contingency coefficient, respectively. RESULTS: Compared with the healthy individuals, the CHD patients showed a significant correlation between MLPH hypermethylation and myocardial infarction (MI) (MLPH_CpG_2.7: P=0.045; MLPH_CpG_3/cg06639874: P=0.049; MLPH_CpG_5: P=0.019), and this correlation was even stronger in individuals below 65 years of age (MLPH_CpG_2.7: P=0.014; MLPH_CpG_4: P=0.001) and in male subjects (MLPH_CpG_2.7: P=0.004; MLPH_CpG_3/cg06639874: P=0.044). The methylation level of TSSC1 gene in peripheral blood was not found to correlate with CHD or its subtypes. CONCLUSIONS Our findings suggest a correlation of MLPH hypermethylation in peripheral blood with CHD and MI in Chinese population, especially in individuals below 65 years and in male individuals.
Humans ; DNA Methylation ; Male ; Female ; Middle Aged ; Case-Control Studies ; Aged ; Coronary Disease/blood* ; Adult ; CpG Islands

The gastrin-releasing peptide receptor(GRPR)is highly expressed in various malignant tumors(e.g.,glioblastoma,prostate cancer,and breast cancer)and has emerged as an important molecular target for precision cancer diagnosis and therapy.In recent years,the combined application of radionuclide-la-beled GRPR ligands with positron emission tomography/computed tomography(PET/CT)has achieved ground-breaking progress in noninvasive diagnosis,accurate staging,and therapeutic monitoring of GRPR-positive tumors.Meanwhile,GRPR-targeted radionuclide therapeutics have demonstrated significant therapeutic potential and promising clinical applications in trials.This GRPR-based theranostic strategy pioneers a novel ap-proach for precision medicine in GRPR-overexpressing tumors.

The gastrin-releasing peptide receptor(GRPR)is highly expressed in various malignant tumors(e.g.,glioblastoma,prostate cancer,and breast cancer)and has emerged as an important molecular target for precision cancer diagnosis and therapy.In recent years,the combined application of radionuclide-la-beled GRPR ligands with positron emission tomography/computed tomography(PET/CT)has achieved ground-breaking progress in noninvasive diagnosis,accurate staging,and therapeutic monitoring of GRPR-positive tumors.Meanwhile,GRPR-targeted radionuclide therapeutics have demonstrated significant therapeutic potential and promising clinical applications in trials.This GRPR-based theranostic strategy pioneers a novel ap-proach for precision medicine in GRPR-overexpressing tumors.

Background: This study aimed to explore relationships between job stress and psychological adaptation and how they related to interpersonal needs through mood states among female migrant manufacturing workers. Methods: A cross-sectional survey was conducted in 16 factories in Shenzhen, China. Sociodemographic, job stress, psychological adaptation and other psychological information of was collected. Structural equation modeling was performed to delineate the internal relationship between variables. Results: The hypothetical structural equation model exhibited acceptable model fit among female migrant manufacturing workers (χ2 = 11.635, df = 2, χ2/df = 5.82, p = 0.003, RMSEA = 0.090, CFI = 0.972, SRMR = 0.020). Job stress was directly associated with mood states and interpersonal needs; Psychological adaptation was directly associated with mood states and indirectly associated with interpersonal needs; Bootstrapping tests demonstrated mediation effect of mood states in the way from psychological adaptation to interpersonal needs. Conclusion Female migrant manufacturing workers who suffered stress from job and the process of psychological adaptation may have worse mood states and workers with worse mood states are more likely to develop unmet interpersonal needs, a proximal factor of suicidal ideation.

Objective:To investigate the value of three-dimensional transvaginal sonography(3D-TVS) in the diagnosis of intrauterine adhesions(IUA) and to analyze the causes of the missed diagnosis.Methods:Forty-seven patients with IUA were examined by three-dimensional transvaginal sonography(3D-TVS), 3D volume imaging (Render imaging) and tomographic ultrasound imaging(TUI imaging) in the Union Hospital of Fujian Medical University from January 2017 to July 2019. The abnormal echo data of the endometrium were recorded and analyzed, and the ultrasound diagnosis and hysteroscopic diagnosis were compared.Results:3D-TVS correctly diagnosed IUA was accurate in the 39 cases whose ultrasound imaging showed an uneven thickness of endometrial echo with the uterine cavity line having different degrees of echo continuity interruption. The diagnostic accuracy rate was 83.0%(39/47). In the Render imaging, 7 cases showed endometrial echo with honeycomb change, 28 cases showed partial echo loss with irregular low echo zone or low echo, and 4 cases showed corneal disappearance of one side. In TUI imaging, the endometrium was partly thinned in varying degrees where echo continuity was interrupted with hypoechoic band-like changes in all 39 cases. Three of the 8 missed IUA cases showed slender endometrium with filiform or membranous adhesions, and the other 5 were patients with uterine endometrial polyps.Conclusions:3D-TVS, Render imaging and TUI imaging technology can display stereo images, which contributes to the better preoperative diagnosis and postoperative follow-up. Care should be taken to avoid missed diagnosis and to improve the diagnostic accuracy for IUA by the techniques.

To discuss the value of color Doppler ultrasonography in the diagnosis and differential diagnosis of ureteral polyps ( U P) . Methods Ninety‐five cases with pathologically proven U P and 104 cases with pathological confirmed urinary tract urothelial carcinoma ( U T UC) were enrolled in the study . T heir positive rate of color Doppler ultrasonography exam preoperatively were retrospectively analyzed and compared with pathological findings . Results Compared with pathological diagnosis , the accordance rate of color Doppler ultrasonography localization were 82 .1% ( 78/95) and 80 .8% ( 84/104) for U P and U T UC respectively ,the accordance rate of qualitative diagnosis were 69 .2% ( 54/78 ) and 90 .5%( 76/84) . Color Doppler ultrasonographic features of U P displayed a clear demarcation between the pipe wall of ureter and surrounding tissue .However ,such clear demarcation could not be found in U T UC . T he accordance rate between two groups has statistically significant difference ( P ＝0 .000 6 ) . Color Doppler ultrasonographic image showed no blood flow in the ureteral polyps ,while mainly minor or medium amount of blood stream signals were found in most tumors of U T UC . According to Adler blood flow grading and the blood flow detective rate ,the two groups demonstrated statistically significant difference ( P ＜0 .05 ) . Conclusions With high resolution color Doppler ultrasonography and flexible operation technique ,it can clearly observe the internal structure of ureter at obstruction end as well as boundary conditions of peripheral tissue ,w hich will play a profound role in preoperative diagnosis and differential diagnosis of U P .

Objective To observe the impairment effect of retinol binding protein 4(RBP4) on neurocognitive function in diabetic nephropathy(DN) patients with silent cerebral infarction(SCI) and to explore its mechanism.Methods Sixty patients with newly diagnosed DN and 30 healthy volunteers were selected as the study subjects and the DN cases were divided into the complicating SCI group(SCI,n=30) and non-complicating SCI group(NSCI,n=30) according to the imaging results.The degrees of neurological function deficit and Montreal cognitive assessment(MoCA) were evaluated.Serum RBP4 level was determined by ELISA and expressions of Lp-PLA2 and C-X-C chemokine receptor type 4(CXCR4) were determined by Western blot.Results Compared with the NSCI group,the neurocognitive function in the SCI group was subsided,the expression levels of RBP4,Lp-PLA2 and CXCR4 were increased(P＜0.05).The RBP4 level was positively correlated with the neurocognitive function impairment in SCI patients,moreover,there existed a regression correlation between them.Conclusion Serum RBP4 may serve as the predictive factor of DN complicating SCI and is positively correlated with neurocognitive dysfunction.Lp-PLA2/CXCR4 pathway activation may be one of its pathogenesis.

Objective: To study the value of three-dimensional(3D) visualization in the diagnosis and surgical treatment for pancreatic tumor. Methods: From June to September 2016, 26 patients with pancreatic tumors in Jinling Hospital, Medical School of Nanjing University were involved. The study included 26 patients(8 females and 18 males) with mean age of (57±12)years (ranging from 23 to 77 years). And there were 20 malignant tumors and 6 benign tumors. All of them were examined with abdominal thin slice CT scanning and the CT images were imported into 3D visualization system for 3D visualization. The main elements examined by 3D visualization included tumor shape, size, and location; distribution and morphology of the peripancreatic lymph node; the relationships among neoplasms, organs and blood vessels. Results: Among the 26 patients, there were 21 cases with pancreatic cancer, of which 15 cases successfully underwent standard pancreatectomy. All patients were operated underwent accurate assessment. The 3D model demonstrated the origination and bifurcations of blood vessels, and the relationships among neoplasms, organs and blood vessels efficiently. The 3D technique could facilitate to evaluate response of neiadjuvant chemotherapy in the pancreatic cancer patients (n=5).3D reconstruction could detect the lymph-node metastases accurately (n=12) in patients with pancreatic cancer. 3D reconstruction were applied to evaluate the the size and range of tumor on 5 cases. Conclusions 3D reconstruction allows stereoscopic identification of the spatial relationships between physiologic and pathologic structures.The 3D technique could facilitate to evaluate distribution and morphology of the peripancreatic lymph node, and to evaluate the relationships among neoplasms, organs and blood vessels.

Objective To observe the effect and efficacy of DPP-4 inhibitor saxagliptin on nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus.Methods Forty patients with newly diagnosed with type 2 diabetes complicated with NAFLD were divided into two groups:the saxagliptin group and the metformin group.On the basis of dietary and exercise therapies,the saxagliptin group received 0.005 g of saxagliptin daily and the metformin treatment group received 0.85-1.70 g of metformin daily.The levels of glycosylated hemoglobin(HbA1 c),triglyceride (TG),blood pressure (BP),alanine aminotransferase (ALT),liver CT and liver/spleen CT were observed before and 3 months after treatment.Results After treatment for 3 months,the TG,ALT,liver CT and liver / spleen CT of the metformin group and the saxagliptin group were significantly higher than those before treatment(P＜0.05).There was no significant difference in the TG,ALT and liver CT values between the two groups(P＞ 0.05).Conclusion In the state of diabetes mellitus complicate with nonalcoholic fatty liver,saxagliptin has a certain effect on relieving fatty liver.