Objective The purpose of this article was to investigate whether the combination of urinary beta 2 microglobulin (urinary β2-MG) and procalcitonin (PCT) diagnosis could enhance the localization diagnostic precision of pediatric urinary tract infection comparing with single diagnosis. Methods A study was conducted in the Nephrology Department of Wuhan women and children's health care centre. This study incorporated 85 participants, including 35 children who were diagnosed as upper urinary tract infection (UUTI) with the symptom of fever and 50 children who conducted lower urinary tract infection (LUTI). Levels of PCT and urinary β2-MG in both UUTI and LUTI patients were measured and compared. Results The level of PCT and β2-MG were both significantly higher in UUTI group compared with in LUTI group. AUC of urinary β2-MG ROC (sensitivity of 71.4%, specificity of 90.0%) was significantly smaller than that of PCT ROC (sensitivity of 77.1%, specificity of 96.0%) in the single diagnosis. Although in the combined diagnosis, the sensitivity and specificity increased to 88.6% and 98%, respectively. Conclusions Both PCT and β2-MG could be used to localize the UTI. Introducing urinary β2-MG into PCT diagnosis could increase the sensitivity and specificity of UTI lesion diagnosis in clinical practice.
Objective
To analyze the correlation between clinical phenotypes and genotypes in 6 children with primary distal renal tubular acidosis (dRTA).
Methods
The clinical data of 6 children confirmed as dRTA in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science & Technology from November 2017 to August 2019 were collected, and related auxiliary examination was performed to assess their growth and development.The venous whole blood was reserved for Trio whole exome sequencing, and full spectrum genetic disease accurate diagnosis cloud platform was applied to systematic data screening and analysis.The suspected mutations were checked by Sanger sequencing, and then the role of protein was predicted by software.
Results
Clinical manifestations, signs and auxiliary examination results of the 6 children accorded with the diagnostic criteria of dRTA, and the prominent characteristics was growth retardation.One case had knee valgus, one had osteoporosis, and the auxiliary examination results showed that both of them had alkaline urine, metabolic acidosis, and hypokalemia.Three children had nephrocalcinosis, and 2 children had nephrolithiasis.The parents of the 6 patients were all normal without phenotypes.Mutations in the SLC4A1 gene were identified in 4 patients, including 1 child with a reported homozygous autosomal recessive missense mutation(c.2102G>A, p.G701D), who had dRTA and hemolytic anemia, and 3 children with the reported de novo heterozygous autosomal dominant missense mutation(c.1766G>A, p.R589H, c.1765C>T, p.R589C), whose age at diagnosis was related to abnormal renal imaging.Compound heterozygous autosomal recessive mutations in the ATPV1B1 gene were identified in 1 patient, and they were novel heterozygous missense mutations (1153C>A, p.P385T and c. 806C>T, p.P269L). A novel homozygous autosomal recessive missense mutation was identified in 1 patient in the ATPV0A4 gene(c.1899C>A, p.Y633X, 208).
Conclusions
Mutations in SLC4A1, ATP6V1B1, ATP6V0A4 genes are identified as the main causes of the primary dRTA, and the phenotypes was related to the mutation features and genotypes.Genetic test should be conducted on patients suspected as dRTA for early molecular diagnosis, thereby improving clinical phenotypic screening and individualized treatment.
Key words:
Distal renal tubular acidosis; Genetic mutation; SLC4A1 gene; ATP6V1B1 gene; ATP6V0A4 gene
Objective
To incorporate 131I i nto the fifth generation polyamidoamine(PAMAM(G5.0)) with the targeting peptide Ser-Arg-Glu-Ser-Pro-His-Pro(SRESPHP)(SR for short) and observe the in vitro properties for the targeting probe of medullary carcinoma cells (MTCs).
Methods
PAMAM (G5.0)-SR and PAMAM(G5.0) were radiolabeled with 131I by chloramine T. Labeling yield and stability were determined by thin layer chromatography. Lipid-water partition coefficients were also evaluated. The targeting of the two types of 131I-radiotracers(131I-PAMAM(G5.0)-SR and 131I-PAMAM(G5.0)) was determined in a blocking uptake study where TT tumor cells were used. The median lethal dose of the two probes was then calculated. GraphPad Prism 5.01 analysis software was used to conduct a t-test for the data that fit the normal distribution and homogeneity of variance.
Results
The labeling yields of the two types of 131I radiotracers all exceeded 70%, and the radiochemical purity levels were higher than 90% after purification. The stability of the two probes in the PBS system was satisfactory, and both probes showed excellent water solubility. The results of the blocking uptake study on the TT cells showed that the cell uptake rate decreased significantly (t=7.315, 22.590, 22.570, all P<0.01) after the PAMAM (G5.0)-SR blocked the 131I-PAMAM (G5.0)-SR. This result indicated that 131I-PAMAM (G5.0)-SR achieved excellent targeting and that its median lethal dose was only 513.6 kBq/mL. The cell uptake results showed that the cell uptake rate of 131I-PAMAM (G5.0)-SR with a median lethal dose gradually decreased with time. However, cell uptake rate increased for 48 h before it decreased again.
Conclusion
131I-PAMAM (G5.0)-SR can target medullary thyroid carcinoma cells and thus inhibit cell proliferation.
Key words:
Iodine radioisotopes; Molecular probes; Medullary thyroid carcinoma; Polyami-doamine; Ser-Arg-Glu-Ser-Pro-His-Pro
Abstract Age-related degeneration of lung tissues increases the risk of lung injury and exacerbates lung disease. It is also the main risk factor for chronic lung diseases (such as COPD, idiopathic pulmonary fibrosis, cancer, etc.). Here, we performed systematic screening, evaluation of elderly macaque model. A senile multiple organ dysfunction model was used to explored whether BMMSC could improve degeneration of lung tissues in an elderly macaque model. Using model evaluation tests, we found that the average alveolar area, Mean linear intercept(MLI) and fibrosis area in the elderly macaque models were significantly larger than in young rhesus monkeys (P <0.05), and the capillary density around the alveoli was significantly lower than in young macaque models (P <0.05). Intraveous infusion of BMMSC reduced the degree of pulmonary fibrosis in elderly macaque, increased the density of capillaries around the alveoli (P <0.05), and the number of type Ⅱ alveolar epithelium in elderly macaque (P <0.05). BMMSC infusion reduced lung tissue ROS level, systemic and lung tissue inflammation level and Treg cell ratio in elderly macaque model(P<0.05). Indirect co-cultivation revealed that BMMSC reduced the expression of senescence-related genes, ROS levels, apoptosis rate of aging type Ⅱ alveolar epithelial cells (A549 cells) and promoted their proliferation (P<0.05).
Thyroid cancer (TC) is a broad classification of neoplasms that includes differentiated thyroid cancer (DTC) as a common histological subtype. DTC is characterized by an increased mortality rate in advanced stages, which contributes to the overall high mortality rate of DTC. This progression is mainly attributed to alterations in molecular driver genes, resulting in changes in phenotypes such as invasion, metastasis and dedifferentiation. Clinical management of DTC is challenging due to insufficient diagnostic and therapeutic options. The advent of‑omics technology has presented a promising avenue for the diagnosis and treatment of DTC. Identifying molecular markers that can predict the early progression of DTC to a late adverse outcome is essential for precise diagnosis and treatment. The present review aimed to enhance our understanding of DTC by integrating big data with biological systems through‑omics technology, specifically transcriptomics and proteomics, which can shed light on the molecular mechanisms underlying carcinogenesis.
Abstract Background: Age-associated lung tissue degeneration is a risk factor for lung injury and exacerbated lung disease. It is also the main risk factor for chronic lung diseases (such as COPD, idiopathic pulmonary fibrosis, cancer, among others).So, it is particularly important to find new anti-aging treatments.Methods: We systematically screened and evaluated elderly senile multiple organ dysfunction macaque models to determine whether BMMSCs inhibited lung tissue degeneration.Results: The average alveolar area, Mean linear intercept(MLI)and fibrosis area in the elderly macaque models were significantly larger than in young rhesus monkeys (p <0.05), while the capillary density around the alveoli was significantly low than in young macaque models (p<0.05). Intravenous infusion of BMMSCs reduced the degree of pulmonary fibrosis, increased the density of capillaries around the alveoli (p <0.05), and the number of type Ⅱ alveolar epithelium in elderly macaques (p <0.05). In addition, the infusion reduced lung tissue ROS levels, systemic and lung tissue inflammatory levels and Treg cell ratio in elderly macaque models(p<0.05). Indirect co-cultivation revealed that BMMSCs suppressed the expression of senescence-associated genes, ROS levels, apoptosis rate of aging type Ⅱ alveolar epithelial cells (A549 cells) and enhanced their proliferation (p<0.05).Conclusions: BMMSC treatment inhibited age-associated lung tissue degeneration.