Objective:To design and develop a molecular imaging probe of 68Ga-labeled bombesin (BBN) analogue, 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-polyethylene glycol (PEG) 4-BBN, and investigate its potential to target prostate cancer with high expression of gastrin-releasing peptide receptor (GRPR) while minimizing uptake in pancreatic tissue. Methods:Based on the amino acid sequence of BBN peptides, the precursor DOTA-PEG 4-BBN was designed and prepared, followed by labeling with 68Ga and conducting to quality control analysis. The tumor uptake of 68Ga-DOTA-PEG 4-BBN was assessed by microPET/CT imaging on tumor-bearing nude mice models with PC3 of high GRPR expression or HT29 of low GRPR expression (3 mice per group). 68Ga-DOTA-PEG 4-BBN microPET/CT imaging was also performed on 6 tumor-bearing nude mice models with PC3, among which 3 mice were treated with gastrin-releasing peptide antagonist 1 h prior to injection of the tracer (blocked group). After imaging, the ex vivo tissues of 3 PC3 tumor-bearing nude mice of the non-blocked group were examined for radioactivity counting to evaluation the biodistribution of 68Ga-DOTA-PEG 4-BBN, and the percentage injected dose per gram of tissue (%ID/g) was calculated. Independent-sample t test was used for data analysis. Results:The synthesis of 68Ga-DOTA-PEG 4-BBN took 40 min, with the radiochemical yield of 50%-60% (no decay correction) and the radiochemical purity of over 95%. After incubation in the serum at 37 ℃ for 4 h, the radiochemical purity remained more than 95%. The microPET/CT imaging results indicated that the uptake in the PC3 tumor was 3.2 times higher than the uptake in the tumor after GRPR blockade ((1.34±0.24) vs (0.42±0.03) %ID/g; t=5.47, P=0.005). After the injection of 68Ga-DOTA-PEG 4-BBN at 1 h and following imaging for 15 min, the PC3 tumor-bearing nude mice models of the non-blocked group showed that the pancreatic uptake ((0.150±0.058) %ID/g) was significantly lower than that in kidneys, lungs and liver ((9.452±0.234), (0.720±0.041), (1.572±0.213) %ID/g) with a profound statistical distinction ( t values: 11.28-53.02, all P<0.001). The tumor/pancreas uptake ratio could reach 16.92 in the tumor-bearing nude mice models with high GRPR expression. Conclusion:A novel molecular imaging probe 68Ga-DOTA-PEG 4-BBN demonstrates specific recognition of tumors with high GRPR expression while exhibiting low uptake in the pancreas, which shows its potential in prostate cancer molecular imaging.

OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with Lesch-Nyhan syndrome. METHODS: Members of the pedigree who had visited the Genetic Counseling Clinic of Linyi People's Hospital on February 10, 2022 were selected as the study subjects. Clinical data and family history of the proband were collected, and trio-whole exome sequencing (trio-WES) was carried out for the proband and his parents. Candidate variants were verified by Sanger sequencing. RESULTS: Trio-WES revealed that both the proband and his cousin brother had harbored a hemizygous c.385-1G>C variant in intron 4 of the HPRT1 gene, which was unreported previously. A heterozygous c.385-1G>C variant of the HPRT1 gene was also found in the proband's mother, grandmother, two aunts, and a female cousin, whilst all phenotypically normal males in his pedigree were found to have a wild type for the locus, which has conformed to an X-linked recessive inheritance. CONCLUSION The heterozygous c.385-1G>C variant of the HPRT1 gene probably underlay the Lesch-Nyhan syndrome in this pedigree.
Male ; Humans ; Female ; Lesch-Nyhan Syndrome/genetics* ; Pedigree ; East Asian People ; Heterozygote ; Introns ; Mutation

Breast cancer is a malignant tumor that seriously threatens women’s health at present. Although surgical treatment is the most direct and effective， it is limited by many factors and needs to be assisted by other treatments. In addition to conventional radiotherapy， these adjuvant therapies also include chemotherapy， gene therapy， phototherapy and so on. However， the therapeutic agents used in these treatment methods have some limitations， such as poor water-solubility， instability and targeting. With the development of nano-technology， more and more researchers construct and study nano delivery system for breast tumor treatment， such as response system designed based on tumor microenvironment， temperature sensitive response system， nano delivery system based on specific proteins of tumor cell membrane， etc. The author summarizes the nano delivery system， and finds that these nano delivery systems can not only improve the water-solubility and stability of the therapeutic agents， but also accurately deliver them to the breast tumor site by targeted means， improve the efficacy and reduce toxic side effects， which provides new ideas for the treatment of breast cancer in the future.

Objective:Based on the principle that the aggregation-induced emission (AIE) fluorescent probe 6PD-DPAN could bind and aggregate with bacteria, and the fluorescence intensity could reflect the quantity of bacteria, a new method for rapid, convenient, and accurate bacterial drug sensitivity testing was established, which provided a basis for rapid and accurate clinical drug use.Methods:This was a methodological evaluation study. A total of 107 clinical isolates were collected from Houjie Hospital of Dongguan City from January to December 2022, among which 46 isolates were used for the establishment of the new method, and 61 isolates were used for methodological validation. The minimum inhibitory concentration (MIC) determined by broth microdilution method was used as the gold standard, and three antibacterial drugs, gentamicin, levofloxacin, and cefotaxime, were used as experimental drugs. The AIE plate was incubated for 4 hours, and the fluorescence intensity was measured every half an hour to draw a fluorescence change curve. The MIC results were compared with the CLSI breakpoints to determine the bacteria as sensitive, intermediate, or resistant. To simplify the detection process, the ratio of fluorescence intensity at 4 hours(R) was calculated, and the ROC curve was used to analyze the efficacy of R in determining bacterial growth and establish its cutoff value. The new method was used to determine the MIC of 61 clinical isolates, with broth microdilution method as the gold standard. The basic consistency, categorical consistency, very major errors, and major errors of the new method were analyzed, and the consistency between the two methods was determined by the Kappa test.Results:ROC curve analysis of the R after 4 hours of culture: The cut-off value was 3.0, with both sensitivity and specificity for determining bacterial growth being 100%. The median (interquartile) R for bacterial growth inhibition was 11.1 (8.6, 14.4); the median R-value for bacterial growth was 1.1 (1.0, 1.2). Compared to the gold standard, the newly established method showed 100% (61/61) essential agreement in detecting MICs of 61 clinical isolates, with a categorical agreement of 96.7% (59/61). There were no very major or major errors, and the Kappa value was 0.94, indicating good consistency between the newly established method and the microbroth dilution method.Conclusions:This study successfully established a new method for bacterial drug sensitivity testing based on AIE technology, which could obtain satisfactory results within 5 hours, providing a basis for early precision drug treatment in clinical practice.

Objective:To compare left and right ventricular Tei indexes and to determine the reference range in newborns of different gestational age (GA) and birth weight (BW).Methods:From February 2019 to June 2021, newborns admitted to the Neonatal Intensive Care Unit of our hospital were enrolled. Tei indexes were measured and calculated during 24 h~7 d after birth and reexamined 1~2 weeks later in some of the newborns. The newborns were assigned into <32 w group, 32~36 w group and ≥ 37 w group according to their GA, < 1 500 g group, 1 500~2 499 g group and ≥2 500 g group according to their BW, and early newborn group (1~7 d) and late newborn group (>7 d) according to their age of evaluation. The data were analyzed using t test, one-way analysis of variance (ANOVA) and correlation analysis with SPSS 20.0 statistical software. Results:A total of 128 cases were included. 42 cases in <32 w group, 43 in 32~36 w group and 43 in ≥37 w group. 42 cases in <1 500 g group, 42 in 1 500 ~ 2 499 g group and 44 in ≥2 500 g group. Tei indexes were reexamined after 7 d of age in 63 preterm infants and in 31 full-term infants. The left and right ventricular Tei indexes of the ≥37 w group were less than the 32~36 w group and the <32 w group in early newborns (left ventricular: 0.382±0.069 vs. 0.431±0.069 and 0.439±0.060, right ventricular: 0.373±0.038 vs. 0.431±0.035 and 0.452±0.064); the right ventricular Tei index of the 32~36 w group was significantly less than the <32 w group ( P<0.05). No significant differences existed in the left ventricular Tei index between the 32 ~ 36 w group and the < 32 w group ( P>0.05). The left and right ventricular Tei indexes of the ≥2 500 g group were significantly less than the 1 500~2 499 g group and the <1 500 g group (left ventricular: 0.385±0.069 vs. 0.434±0.067 and 0.434±0.064, right ventricular: 0.376±0.039 vs. 0.431±0.043 and 0.450±0.061) ( P<0.05).No significant differences existed between the 1 500~2 499 g group and the <1 500 g group ( P>0.05). No significant differences existed in the left and right ventricular Tei indexes between the late newborn group and early newborn group ( P>0.05). For early newborns (1~7 d of age), the reference range of Tei index gradually decreased along with the increase of GA and BW. Conclusions:The left and right ventricular Tei indexes of full-term infants and infants with BW ≥2 500 g are less than preterm and low birth weight infants. The reference range of Tei index in early newborns shows negative correlation with GA and BW.

Objective:To investigate the predictive value of matrix metalloproteinase-9 (MMP-9) and neutrophil to lymphocyte ratio (NLR) in delayed perihematomal edema (dPHE) after spontaneous intracerebral hemorrhage (sICH).Methods:Patients with sICH admitted to Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School within 24 h of onset from January 2018 to June 2020 were enrolled retrospectively. Serum MMP-9 levels and peripheral blood cell counts were detected, and NLR were calculated within 24 h of onset. dPHE was defined as an increase of 3 ml in absolute edema volume at 10-21 d after onset of sICH compared with that at 5-9 d. The demographic and baseline clinical and imaging data of the dPHE group and the non-dPHE group were compared. Multivariate logistic regression analysis was used to identify the independent predictors of dPHE. The receiver operating characteristic (ROC) curve was used to evaluate the predictive values of MMP-9 and NLR for dPHE. Results:A total of 195 patients with sICH (61.88±10.60 years old) were enrolled in the study. One hundred and forty-eight patients were males (75.9%). There were 53 patients (27.2%) in the dPHE group and 142 (72.8%) in the non-dPHE group. Univariate analysis showed that age, baseline hematoma volume, baseline National Institutes of Health Stroke Scale score, fasting blood glucose, high-sensitivity C-reactive protein, MMP-9, neutrophil count, NLR and the proportion of irregular hematoma in the dPHE group were significantly higher than those in the non-dPHE group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for confounding factors, higher MMP-9 (odds ratio [ OR] 4.291, 95% confidence interval [ CI] 2.041-6.590; P=0.007) and higher NLR ( OR 2.530, 95% CI 1.157-4.022; P=0.011) were all the independent predictors of dPHE. ROC curve analysis showed that the area under the curve of MMP-9 for predicting dPHE was 0.819 (95% CI 0.756-0.884; P<0.001), the optimal cut-off value was 164.0 μg/L, and the sensitivity and specificity were 86.79% and 66.90% respectively. The area under the curve of NLR for predicting dPHE was 0.788 (95% CI 0.719-0.856; P<0.001), the optimal cut-off value was 5.683, and the corresponding sensitivity and specificity were 77.36% and 71.13% respectively. Conclusions:sICH patients with higher baseline MMP-9 and NLR are more likely to develop dPHE. Early detection of MMP-9 and NLR in peripheral blood after admission can predict dPHE.

Objective:To investigate the role of DDX3 up-regulation in the proliferation of human cervical cancer cells and its correlation with clinical prognosis.Methods:Expression levels of DDX3 in the 59 specimens of cervical cancer and adjacent non-neoplastic tissue collected at Henan Provincial People′s Hospital from April 2012 to March 2013 were detected using immunohistochemistry. A lentivirus-mediated DDX3-over-expression cell line was constructed based on HeLa cells of cervical cancer. CCK-8 assay was used to evaluate cell survival rate. Boyden chamber was used to measure the cell migration and invasion. Real-time fluorescence quantitative PCR was used to detect DDX3 expression level and Western blot was used to detect the expression of EMT and PI3K/Akt signal pathway-related proteins. Results:DDX3 overexpression was associated with FIGO stage, depth of cervical invasion and lymph node metastasis ( P<0.05). Kaplan-Meier analysis revealed that cervical cancer patients with high expression of DDX3 had a poor overall survival ( P<0.05). Compared with the cells transfected with pLVX-Con vector, the expression of DDX3 protein and mRNA was significantly increased in the cells transfected with pLVX-DDX3 (all P<0.01). Cell proliferation was significantly increased following transfection with pLVX-DDX3 for 72 h in HeLa cells compared with that transfected with pLVX-Con ( P<0.05). Compared with the controls, DDX3 overexpression significantly promoted the migration and invasion of HeLa cells ( P<0.05), and increased the expression of N-Cadherin, vimentin and Snail in HeLa cells ( P<0.05). In pLVX-DDX3 group, the expression levels of β-catenin, phosphorylated Akt, and pAkt′s downstream target p-GSK3β were significantly higher than those of pLVX-Con group ( P<0.05). The expression levels of p-Akt, p-GSK3β and β-catenin were decreased when the PI3K/Akt pathway was blocked using the PI3K inhibitor LY294002 ( P<0.05), and the expression levels of N-Cadherin, vimentin and Snail were also significantly decreased ( P<0.05). Conclusions:DDX3 overexpression promotes proliferation, migration and invasion of cervical cancer cells, and induces epithelial-mesenchymal transition (EMT). Its mechanism may be related to activation of the PI3K/Akt signaling pathway.

Breast cancer is one of the most serious diseases threatening women's life and health in the world, and the mortality rate is the second in the world. With the progress of nanotechnology and the advantages of nanomaterials in the field of electrochemistry and biosensor, various nanomaterials have been applied in electrochemical biosensors. This makes the electrochemical nano-biosensor in the field of rapid detection of breast cancer has been widely concerned and studied. This paper introduces the important components of electrochemical nano-biosensor for breast cancer detection and the research progress of each component in breast cancer detection, as well as the performance of electrochemical nano biosensor in breast cancer detection and the prospect of its application.
Biosensing Techniques ; Breast Neoplasms/diagnosis* ; Electrochemical Techniques ; Female ; Humans ; Nanostructures ; Nanotechnology

Objective: To investigate the clinicopathological characteristics, histogenesis, immunophenotypes, molecular genetic characteristics, diagnosis and differential diagnosis of calcifying fibrous tumors (CFT). Methods: A total of 32 cases of CFT (22 cases from Henan Provincial People′s Hospital and 10 cases from PLA Army Medical Center) diagnosed between June 2009 and February 2019 were reviewed. The clinical and pathologic data were analyzed. Results: There were 12 male and 20 female patients, aged from 15 to 63 years (mean 40.8 years). Eleven cases occurred in stomach, four cases in retroperitoneum, four cases in ovary, two cases in scrotum, two cases in mediastinum, two cases in head and neck, one case each in thoracic cavity, lung, adrenal gland, kidney, sigmoid colon, epididymis and mesosalpinx. All the tumors were solid masses with clear boundaries. The maximal dimension of the tumors ranged from 0.6 to 10.0 cm. Microscopically, there was hypocellular stromal sclerosis and wavy storiform coarse collagen with superimposed scattered or patchy lymphocytes and plasma cells; calcification or gravel formation were also detected. Immunohistochemistry showed that spindle cells were positive for vimentin and some were positive for CD34; and they were negative for calponin, SMA, desmin, S-100 protein, SOX10, STAT6, β-catenin, ALK, CD117, DOG1, CKpan, and EMA. No ALK rearrangement was detected by FISH in all cases. No C-KIT and PDGFRA mutation was detected in all the tested 11 cases of stomach, four cases of retroperitoneal and one case of sigmoid colon CFT. MDM2 was not amplified by FISH in all four tested cases of retroperitoneal CFT. Conclusions CFT is a rare benign tumor of fibroblastic cell origin. The diagnosis mainly depends on histomorphologic analysis and immunophenotyping. CFT should be differentiated from other benign and malignant spindle cell mesenchymal tumors.

At present, there are many monitoring devices for vital signs parameters for clinical selection, but urine monitoring has not received enough attention. The traditional manual visual measurement, intermittent measurement of urine pH value, and other methods are still in use, so the authors designed a multifunctional urine bag. The urine bag can set up an alarm system per unit time according to patient′s age and condition as well as set up urine pH value detection area in hard plastic measuring bottle. This device can not only accurately monitor urine volume per unit time, but also hopefully realize the alarm automation of abnormal urine volume per unit time, as well as real-time dynamic monitoring of urine pH value. It is helpful for medical staff to make accurate judgment on patients′ condition changes, to guide the formulation and modification of clinical treatment plans, and to reduce the workload of clinical nursing staff to a certain extent.