Objective:To study the diagnostic value of artificial intelligence B-ultrasound image computer-aided diagnosis system (hereinafter referred to as intelligent ultrasound system) in adult goiter.Methods:In June 2022 and March 2023, two phases of thyroid disease survey were carried out in 4 cities in Anhui Province. One village was selected in each city, and 250 adults were selected as survey subjects in each village. Adult bilateral thyroid area was scanned by both intelligent ultrasound system and conventional ultrasound scanning equipment, and the effectiveness of intelligent ultrasound system in the diagnosis of goiter was analyzed based on the results of conventional ultrasound examination. Receiver operating characteristic (ROC) curve was drawn, and Kappa test was used to analyze the consistency between intelligent ultrasound system and conventional ultrasound examination in the diagnosis of goiter. At the same time, Spearman correlation analysis and Bland-Altman method were used to evaluate the consistency of the two methods in measuring thyroid volume.Results:After screening and removing outliers and missing values, a total of 910 adults were included, including 253 males (27.80%) and 657 females (72.20%). The age was (45.92 ± 10.20) years old, ranging from 18 to 60 years old. The sensitivity, specificity, and accuracy of the intelligent ultrasound system for diagnosing adult goiter were 80.00%, 99.67%, and 99.56%, respectively. The area under the ROC curve (AUC) was 0.996, which was consistent with the results of conventional ultrasound examination for diagnosing goiter ( κ = 0.67, P < 0.001). After controlling for variables such as gender, thyroid function, and thyroid nodules, the intelligent ultrasound system showed good consistency with conventional ultrasound examination in the diagnosis of goiter in females, adults with thyroid dysfunction, and adults without thyroid nodules ( κ = 0.66, 0.80, 0.80, P < 0.001). The consistency in the diagnosis of goiter in adults with thyroid nodules was moderate ( κ = 0.56, P < 0.001). Spearman correlation analysis showed a highly positive correlation between the measurement results of adult thyroid volume by intelligent ultrasound system and conventional ultrasound examination ( r = 0.88, P < 0.001). The Bland-Altman method results showed that only 4.62% (42/910) of points in adults were outside the 95% consistency limit, indicating good consistency between intelligent ultrasound system and conventional ultrasound examination in measuring thyroid volume (< 5%). The proportion of points outside the 95% consistency limit in males, adults with thyroid dysfunction, and adults with thyroid nodules was 6.72% (17/253), 5.83% (12/206), and 6.45% (12/186), respectively. Conclusions:The intelligent ultrasound system has certain diagnostic value for adult goiter and has good consistency with conventional ultrasound examination for thyroid volume measurement. However, the accuracy of diagnosis for males and adults with thyroid nodules still needs to be improved.

Objective To compare the effectiveness of Defocus Incorporated Multiple Segments (DIMS) and High Aspheric Lenslet (HAL) defocus lenses in controlling myopia. Methods A total of 214 children and adolescents who were fitted with defocus lenses (DIMS or HAL) in our hospital from January to June 2023 were selected, including 100 cases in DIMS group and 114 cases in the HAL group. Changes in parameters such as spherical lens power, cylindrical lens power, spherical equivalent (SE), corneal curvature (K), axial length (AL), binocular accommodative response (BCC), positive/negative relative accommodation (PRA/NRA), distance/near latent phoria (DLP/NLP), and accommodative convergence to accommodation ratio (AC/A) were compared between the two groups before wearing and after wearing the lenses for 6 months, and the effectiveness of myopia control between DIMS and HAL was further compared. Results After wearing the lenses (DIMS or HAL) for 6 months, the average increase in axial length was (0.09±0.14) mm, the average increase in spherical lens power was (-0.11±0.23) D, the average increase in astigmatism was (-0.07±0.16) DC, and the average increase in spherical equivalent was (-0.15±0.24) D, with statistically significant differences observed for all these changes (t=9.24, -7.27, -6.60, -9.03, respectively, P < 0.001). Compared with parameters before wearing the lenses, statistically significant differences were noted after wearing for 6 months in spherical lens power, cylindrical lens power, SE, BCC, PRA, DLP, average K, and AL (P≤0.001), except for NRA (t=-0.12, P>0.05), NLP (t=-0.28, P>0.05), and AC/A (t=0.33, P>0.05). The differences in parameters between the two groups after wearing the lenses for 6 months showed a statistically significant difference only in the AL difference (t=4.38, P≤0.001), with no statistically significant differences observed for other parameter differences (P>0.05). Conclusion Wearing defocus lenses has a positive effect on controlling myopia, delaying axial length elongation, and maintaining binocular visual function balance.

Objective: To analyze the phenotype and genotype of two pedigrees with inherited fibrinogen (Fg) deficiency caused by two heterozygous mutations. We also preliminarily probed the molecular pathogenesis. Methods: The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and plasma fibrinogen activity (Fg∶C) of all family members (nine people across three generations and three people across two generations) were measured by the clotting method. Fibrinogen antigen (Fg:Ag) was measured by immunoturbidimetry. Direct DNA sequencing was performed to analyze all exons, flanking sequences, and mutated sites of FGA, FGB, and FGG for all members. Thrombin-catalyzed fibrinogen polymerization was performed. ClustalX 2.1 software was used to analyze the conservatism of the mutated sites. MutationTaster, PolyPhen-2, PROVEAN, SIFT, and LRT online bioinformatics software were applied to predict pathogenicity. Swiss PDB Viewer 4.0.1 was used to analyze the changes in protein spatial structure and molecular forces before and after mutation. Results: The Fg∶C of two probands decreased (1.28 g/L and 0.98 g/L, respectively). The Fg∶Ag of proband 1 was in the normal range of 2.20 g/L, while it was decreased to 1.01 g/L in proband 2. Through genetic analysis, we identified a heterozygous missense mutation (c.293C>A; p.BβAla98Asp) in exon 2 of proband 1 and a heterozygous nonsense mutation (c.1418C>G; p.BβSer473*) in exon 8 of proband 2. The conservatism analysis revealed that Ala98 and Ser473 presented different conservative states among homologous species. Online bioinformatics software predicted that p.BβAla98Asp and p.BβSer473* were pathogenic. Protein models demonstrated that the p.BβAla98Asp mutation influenced hydrogen bonds between amino acids, and the p.BβSer473* mutation resulted in protein truncation. Conclusion: The dysfibrinogenemia of proband 1 and the hypofibrinogenemia of proband 2 appeared to be related to the p.BβAla98Asp heterozygous missense mutation and the p.BβSer473* heterozygous nonsense mutation, respectively. This is the first ever report of these mutations.
Humans ; Afibrinogenemia/genetics* ; Codon, Nonsense ; Pedigree ; Phenotype ; Fibrinogen/genetics* ; Genotype

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

ObjectiveTo establish a traditional Chinese medicine （TCM） syndrome model with yin deficiency and internal heat， discuss the rationality of model evaluation， and analyze differentially expressed genes in multiple dimensions to explore the molecular mechanism-signaling pathways as well as key targets of Baihe Dihuangtang （BHDH） in treating depression with Yin deficiency and internal heat. MethodForty male SD rats were randomly divided into a blank control group，a model group，a fluoxetine group （positive drug），a BHDH group， and a Zhibai Dihuangtang group （positive drug for Yin deficiency and internal heat）. The depression model with Yin deficiency and internal heat was induced by chronic unpredictable mild stress （CUMS）combined with Chinese herbal drugs with warm and heat nature. The model established was comprehensively evaluated by the detection of the basic condition， behavioral performance， and biochemical indicators of rats in each group. The differentially expressed genes were screened out by mRNA sequencing and underwent Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analyses. The protein-protein interaction （PPI） network was plotted and key genes were analyzed to explore the underlying mechanism of BHDH in treating depression with Yin deficiency and internal heat. ResultThe comparison of basic conditions， behavioral assays， energy metabolism， endocrine hormones， cytokines， and neurotransmitters showed that the model was properly induced. BHDH could significantly improve depression with Yin deficiency and internal heat by regulating the pathways related to the nervous system， endocrine system， and inflammatory and immune system. The key genes of the PPI network were Fos， Epha8， Npy2r， Htr2c， and Nr4a1. ConclusionUnder the guidance of TCM theories of treatment based on syndrome differentiation and etiology and pathogenesis，this study established a depression model with yin deficiency and internal heat in animals and evaluation system in accordance with the symptoms and signs of emotional diseases， and further confirmed the scientificity of the modeling method and the underlying mechanism of BHDH in interfering with depression with Yin deficiency and internal heat based on the results of mRNA sequencing.

Objective To observe the distribution of mesencephalic astrocyte derived neurotrophic factor (MANF) within the brain in human, mice and rats and the comparison across the species. Methods An immunohistochemical method was applied to investigate the expression of MANF and to compare the differences among species in the brain of human specimens ( n = 5) , mice ( n = 6) , and rats ( n = 6). Results The expression of MANF varied in different brain regions in human, mice and rats. In human, in the cortex, the expression of MANF was the highest among all brain regions. In the subcortical areas or the nucleus, brainstem and cerebellum expression level of MANF were relatively lower. The distribution of MANF in mouse and rat brain were slightly different from that in human brain, but generally consistent. Conclusion The distribution pattern of MANF is similar across the species, however, within a species, MANF expression levels varies in different brain regions.

OBJECTIVE: To study the expression and diagnostic value of plasma miR-145 and miR-183 in children with lupus nephritis (LN). METHODS: A total of 92 children with LN who were admitted from January 2016 to May 2019 were enrolled as the LN group, among whom 17 had type II LN, 15 had type III LN, 36 had type IV LN, 18 had type V LN, and 6 had type VI LN. Forty healthy children who underwent physical examination were enrolled as the healthy control group. According to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the 92 children with LN were further divided into a stable LN group with 34 children (SLEDAI score <10) and an active LN group with 58 children (SLEDAI score ≥10). RT-PCR was used to measure the expression of miR-145 and miR-183 in plasma. The receiver operating characteristic (ROC) curve was used to analyze the value of plasma miR-145, miR-183, and anti-dsDNA antibody in the diagnosis of LN. Pearson correlation analysis was used to investigate the correlation of the expression levels of miR-145 and miR-183 in plasma with laboratory markers. RESULTS: The LN, active LN, and stable LN groups had significantly higher levels of anti-dsDNA antibody, C-reactive protein, serum creatinine (Scr), and blood urea nitrogen (BUN) than the control group (P<0.05). The active LN group had significantly higher SLEDAI score, anti-dsDNA antibody, Scr, and BUN than the stable LN group (P<0.05). The LN, active LN, and stable LN groups had significantly lower levels of complement C3, complement C4, and serum albumin (Alb) than the control group (P<0.05). The active LN group had a significantly lower level of Alb than the stable LN group (P<0.05). The LN, active LN, and stable LN groups had significantly lower plasma levels of miR-145 and miR-183 than the control group (P<0.01). The active LN group had significantly lower plasma levels of miR-145 and miR-183 than the stable LN group (P<0.01). The children with difference types of LN had significantly lower plasma levels of miR-145 and miR-183 than the control group (P<0.01), and the type V-VI group and the type IV group had significantly lower plasma levels of miR-145 and miR-183 than the type II-III group (P<0.01). The ROC curve analysis showed that the optimal cut-off values of plasma miR-145, miR-183, and anti-dsDNA antibody were 1.05, 0.62, and 186.30 IU/mL respectively, in the diagnosis of LN, and the combination of these three indices had the largest area under the ROC curve of 0.896 (95%CI: 0.835-0.955), with a sensitivity of 90.5% and a specificity of 84.2%. In the children with LN, the plasma levels of miR-145 and miR-183 were negatively correlated with SLEDAI score, anti-dsDNA antibody, Scr, and BUN (P<0.05) and were positively correlated with complement C3, complement C4, and Alb (P<0.05). CONCLUSIONS There are significant reductions in the expression levels of miR-145 and miR-183 in plasma in children with LN, which are correlated with the activity level and pathological typing of LN. Combined measurement of miR-145, miR-183, and anti-dsDNA antibody has a high value in the diagnosis of LN.
Biomarkers ; Child ; Complement C4 ; Humans ; Lupus Nephritis ; genetics ; MicroRNAs ; genetics ; ROC Curve

Objective To investigate the clinical and molecular biological characteristics of mixed_phenotypic acute leukemia (MPAL) with SET_NUP214 fusion gene positive and extramedullary infiltration. Methods The clinical characteristics, diagnosis and treatment of one MPAL patient with SET_NUP214 and extramedullary infiltration who was admitted to Hebei Yanda Ludaopei Hospital in November 2017 were analyzed, and the literature was reviewed. Results The patient was diagnosed as MPAL with extramedullary infiltration. Gene detection found SET exon7_NUP214 exon17 fusion positive accompanied with PHF6, SRSF2 and NRAS mutations. After intensive chemotherapy, the patient achieved complete remission, and then received hematopoietic stem cell transplantation (HSCT), followed by early extramedullary relapse after transplantation, and achieved secondary remission after consolidation chemotherapy. Conclusions MPAL with SET_NUP214 fusion gene positive and extramedullary infiltration has a poor prognosis, and it is easy to relapse. Currently, HSCT is the best available treatment strategy for such patients.

The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of ‘personalised’ medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore.We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy.We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.
Hope ; Humans ; Lutetium ; Membranes ; Nuclear Medicine ; Prostate ; Radium ; Receptors, Peptide ; Singapore ; Theranostic Nanomedicine ; Yttrium

The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of ‘personalised’ medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore.We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy.We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.