Objective To evaluate the efficiency of intra-tumor and peri-tumor ultrasound radiomics models based on machine learning algorithms for predicting benign and malignant Breast Imaging Reporting and Data System (BI-RADS) 4 breast lesions, and provide insights into early diagnosis of breast cancer. Methods A retrospective analysis was conducted based on the medical records of 450 female patients who underwent breast ultrasound examination in the Affiliated Cancer Hospital of Xinjiang Medical University from June 2020 to April 2022. The patients were divided into the benign (n = 199) and malignant (n = 195) groups according to pathological examination, and randomized into the training (n = 275) and validation (n = 119) sets at a ratio of 7∶3. Radiomics features were extracted and screened. Intra-tumor, peri-tumor, and intra-tumor + peri-tumor ultrasound radiomics models were constructed based on three machine learning algorithms, including logistic regression (LR), support vector machine (SVM), and multi-layer perceptron (MLP). Receiver operating characteristics (ROC) curves, calibration curves, and decision curves were plotted to evaluate the efficacy of the radiomics models for prediction of benign and malignant breast lesions. Results A total of 17 intra-tumor, 16 peri-tumor, and 17 intra-tumor + peri-tumor radiomics features were selected for model construction. Based on LR, MLP, and SVM algorithms, the intra-tumor + peri-tumor radiomics models showed higher predictive efficacy than intra-tumor and peri-tumor radiomics models. The predictive efficacy of intra-tumor, peri-tumor, and intra-tumor + peri-tumor radiomics models were higher based on the SVM algorithm than based on LR and MLP algorithms. For the intra-tumor radiomics model based on the SVM algorithm, the area under the ROC curve (AUC), accuracy, sensitivity, and a specificity were 0.909, 0.851, 0.860, and 0.842, respectively, in the training set and 0.866, 0.832, 0.847, and 0.817, respectively, in the validation set. For the peri-tumor radiomics model based on the SVM algorithm, these values were 0.899, 0.855, 0.882, and 0.827, respectively, in the training set and 0.844, 0.815, 0.847, and 0.783, respectively, in the validation set. For the intra-tumor + peri-tumor radiomics model based on the SVM algorithm, these values were 0.943, 0.876, 0.860, and 0.892, respectively, in the training set and 0.881, 0.849, 0.915, and 0.783, respectively, in the validation set. Conclusion The intra-tumor and peri-tumor ultrasound radiomics models based on machine learning algorithms are highly valuable for prediction of benign and malignant BI-RADS 4 breast lesions. The intra-tumor + peri-tumor ultrasound radiomics model based on the SVM algorithm has the optimal efficacy for prediction of benign and malignant BI-RADS 4 breast lesions.

ObjectiveTo investigate the perceived experience and acceptance of intrapartum ultrasound （IPUS） as a novel method for labor progress assessment among pregnant women. MethodsFrom February 2023 to December 2024， a total of 180 pregnant women admitted to the Labor Ward of Lingnan Hospital， the Third Affiliated Hospital of Sun Yat-sen University， who were planned for vaginal trial of labor ， were accessed for labor progress using IPUS and vaginal examination （VE） after the onset of labor and prior to the initiation n of labor analgesia. A self-designed questionnaire was used to investigate the women's perceived experiences with both examination methods and their acceptance of IPUS. The pain intensity associated with the examinations was evaluated using the visual analogue pain scale （VAS）. Differences in the women's experiences and pain intensity between the two labor progress assessment methods were compared. ResultsThe acceptance rate of IPUS was 96.67% （174/180）， with the remaining 6 cases undecided. Over 60% of the pregnant women reported IPUS assessment as comfortable and none of them felt discomfort， whereas 32.8% felt uncomfortable with VE （χ²=196.02， P＜0.001）. Nearly two-thirds of the pregnant women believed that VE would cause psychological distress， while none reported such effect with IPUS （χ²=261.52， P＜0.001）. Approximately 77.78% （140/180） of the pregnant women believed that IPUS could reduce their fear of vaginal delivery and enhance their confidence if it replaced VE. The VAS score for IPUS ［0 （0， 2）］ was significantly lower than that for VE ［4 （4， 6）］ （Z=-14.62， P＜0.001）. Further stratified analysis showed that over 90% （164/180） of the pregnant women found IPUS painless， with no moderate or severe pain reported， compared to 43.33% （78/180） experienced moderate or severe pain with VE （P＜0.001）. ConclusionAs a novel approach for labor progress assessment， IPUS not only alleviates the pain and discomfort associated with traditional VE and reduces the fear of childbirth but also enhances women's confidence in delivery， thereby achieving a high level of acceptance among parturient women in China.

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

Attempts have been made to modulate motor sequence learning (MSL) through repetitive transcranial magnetic stimulation, targeting different sites within the sensorimotor network. However, the target with the optimum modulatory effect on neural plasticity associated with MSL remains unclarified. This study was therefore designed to compare the role of the left primary motor cortex and the left supplementary motor area proper (SMAp) in modulating MSL across different complexity levels and for both hands, as well as the associated neuroplasticity by applying intermittent theta burst stimulation together with the electroencephalogram and concurrent transcranial magnetic stimulation. Our data demonstrated the role of SMAp stimulation in modulating neural communication to support MSL, which is achieved by facilitating regional activation and orchestrating neural coupling across distributed brain regions, particularly in interhemispheric connections. These findings may have important clinical implications, particularly for motor rehabilitation in populations such as post-stroke patients.
Humans ; Transcranial Magnetic Stimulation ; Motor Cortex/physiology* ; Male ; Electroencephalography ; Neuronal Plasticity/physiology* ; Female ; Adult ; Evoked Potentials, Motor/physiology* ; Young Adult ; Learning/physiology*

Nitrate is the main form of inorganic nitrogen that crop absorbs, and nitrate transporter 2 (NRT2) is a high affinity transporter using nitrate as a specific substrate. When the available nitrate is limited, the high affinity transport systems are activated and play an important role in the process of nitrate absorption and transport. Most NRT2 cannot transport nitrates alone and require the assistance of a helper protein belonging to nitrate assimilation related family (NAR2) to complete the absorption or transport of nitrates. Crop nitrogen utilization efficiency is affected by environmental conditions, and there are differences between varieties, so it is of great significance to develop varieties with high nitrogen utilization efficiency. Sorghum bicolor has high stress tolerance and is more efficient in soil nitrogen uptake and utilization. The S. bicolor genome database was scanned to systematically analyze the gene structure, chromosomal localization, physicochemical properties, secondary structure and transmembrane domain, signal peptide and subcellular localization, promoter region cis-acting elements, phylogenetic evolution, single nucleotide polymorphism (SNP) recognition and annotation, and selection pressure of the gene family members. Through bioinformatics analysis, 5 NRT2 gene members (designated as SbNRT2-1a, SbNRT2-1b, SbNRT2-2, SbNRT2-3, and SbNRT2-4) and 2 NAR2 gene members (designated as SbNRT3-1 and SbNRT3-2) were identified, the number of which was less than that of foxtail millet. SbNRT2/3 were distributed on 3 chromosomes, and could be divided into four subfamilies. The genetic structure of the same subfamilies was highly similar. The average value of SbNRT2/3 hydrophilicity was positive, indicating that they were all hydrophobic proteins, whereas α-helix and random coil accounted for more than 70% of the total secondary structure. Subcellular localization occurred on plasma membrane, where SbNRT2 proteins did not contain signal peptides, but SbNRT3 proteins contained signal peptides. Further analysis revealed that the number of transmembrane domains of the SbNRT2s family members was greater than 10, while that of the SbNRT3s were 2. There was a close collinearity between NRT2/3s of S. bicolor and Zea mays. Protein domains analysis showed the presence of MFS_1 and NAR2 protein domains, which supported executing high affinity nitrate transport. Phylogenetic tree analysis showed that SbNRT2/3 were more closely related to those of Z. mays and Setaria italic. Analysis of gene promoter cis-acting elements indicated that the promoter region of SbNRT2/3 had several plant hormones and stress response elements, which might respond to growth and environmental cues. Gene expression heat map showed that SbNRT2-3 and SbNRT3-1 were induced by nitrate in the root and stem, respectively, and SbNRT2-4 and SbNRT2-3 were induced by low nitrogen in the root and stem. Non-synonymous SNP variants were found in SbNRT2-4 and SbNRT2-1a. Selection pressure analysis showed that the SbNRT2/3 were subject to purification and selection during evolution. The expression of SbNRT2/3 gene and the effect of aphid infection were consistent with the expression analysis results of genes in different tissues, and SbNRT2-1b and SbNRT3-1 were significantly expressed in the roots of aphid lines 5-27sug, and the expression levels of SbNRT2-3, SbNRT2-4 and SbNRT3-2 were significantly reduced in sorghum aphid infested leaves. Overall, genome-wide identification, expression and DNA variation analysis of NRT2/3 gene family of Sorghum bicolor provided a basis for elucidating the high efficiency of sorghum in nitrogen utilization.
Nitrate Transporters ; Nitrates/metabolism* ; Sorghum/metabolism* ; Anion Transport Proteins/metabolism* ; Phylogeny ; Protein Sorting Signals/genetics* ; Nitrogen/metabolism* ; DNA ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism*

Objective:To analyze the lipid levels, adverse perinatal outcome and their correlation in Tibetan pregnant women in high altitudes in late pregnancy.Methods:Retrospective analysis was performed on clinical and laboratory data of 523 Tibetan singleton pregnant women who delivered after 28 weeks at the Department of Obstetrics and Gynecology, Chaya People's Hospital, Changdu City. The subjects were divided into three groups according to the altitude of their long-term residence, including altitude<3 500 m (Group A, n=161), altitude ≥3 500 m and <4 000 m (Group B, n=203) and altitude≥4 000 m (Group C, n=159). In addition, the subjects were also grouped into high TG group (TG≥3.23 mmol/L, n=80) and control group (TG<3.23 mmol/L, n=443). The baseline information, levels of lipid and perinatal outcome were compared among Group A,B and C, and also between the high TG and control group, respectively, using Mann-whitney U test, Kruskal-Wallis H test, LSD- t, Chi-square test, or Fisher exact test. Multivariate logistic regression analysis was also applied to analyze the correlation between hypertriglyceridemia and adverse perinatal outcome. Results:The maternal age, gravidity and parity, body mess index, blood pressure on admission and total cholesterol (TC), TG, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), TG/HDL-C ratio and LDL-C/HDL-C ratio in late pregnancy and the occurrence of adverse perinatal outcome did not show any significant differences among Group A, B and C (all P>0.05). However, the hemoglobin (Hb) level increased with the elevation of altitude as expected, and that in Group C was higher than that in Group A and B [121.0 g/L (108.0-132.0 g/L) vs 115.0 g/L (103.5-128.0 g/L) and 117.0 g/L (101.0-127.0 g/L), H=2.37 and 1.97, both P<0.05]. The proportion of women with hypertriglyceridemia, the high TG group, in late pregnancy was 15.3% (80/523), and no significant difference was found in HDL-C or Hb levels between the high TG and control group [1.7 mmol/L (1.5-2.0 mmol/L) vs 1.8 mmol/L (1.5-2.1 mmol/L), Z=－1.51;123.5 g/L (110.0-131.8 g/L) vs 117.0 g/L (104.0-128.0 g/L), Z=1.69; both P>0.05]. Higher rates of cesarean section [13.8% (11/80) vs 6.6% (29/443), χ2＝4.98], hypertensive disorders of pregnancy (HDP) [16.3% (13/80) vs 7.5% (33/443), χ2＝6.54], preeclampsia (PE) [8.8% (7/80) vs 1.6% (7/443), χ2＝13.37], hyperglycemia during pregnancy [11.3%( 9/80) vs 3.6% (16/443), χ2＝8.69], preterm birth (PB) [7.5% (6/80) vs 2.0% (9/443), χ2＝7.27], microsomia [5.0% (4/80) vs 0.9% (4/443), Fisher exact test] and neonatal asphyxia [8.8%(7/80) vs 2.5% (11/443), χ2＝8.01] were observed in the high TG group than in the control group (all P<0.05). Regarding the pregnant women at different altitude, TG was negatively correlated with Hb ( r=－0.17, P=0.037) only in Group C .Multivariate logistic regression analysis revealed higher risk of HDP ( OR=2.42,95% CI:1.17-5.00), PE ( OR=5.25, 95% CI:1.73-16.00), hyperglycemia during pregnancy ( OR=3.77, 95% CI:1.56-9.09), PB ( OR=4.33, 95% CI:1.42-13.22), microsomia ( OR=4.33, 95% CI:1.42-13.22), neonatal asphyxia ( OR=3.45, 95% CI:1.27-9.35) and fetal demise ( OR=4.94, 95% CI:1.01-24.21) in women with high TG level in late pregnancy (all P<0.05). Conclusions:There were no differences in adverse perinatal outcomes or serum lipid levels in late pregnancy among women living at different high altitudes. However, hypertriglyceridemia at the third trimester is closely associated with the incidence of HDP, PE, hyperglycemia during pregnancy, PB, microsomia, neonatal asphyxia and fetal demise in this group of women.

Objective:To explore the associations between thyroid function in the first trimester in twin pregnancies and gestational diabetes mellitus (GDM) and the risk factors of twin pregnancies complicated by GDM.Methods:Retrospective analysis was performed on 745 twin pregnancies delivered after 28 weeks at the Third Affiliated Hospital of Sun Yat-sen University from January 2015 to December 2021, and they were divided into GDM group ( n=186) and the control (non-GDM) group ( n=559). Thyroid dysfunction was diagnosed based on the reference range of singleton and twin pregnancies recommended by the Guideline on diagnosis and management of thyroid diseases (2nd edition) in China and the literature, respectively. Independent sample t-test, Chi-square test, or Fisher exact test, and Mann-Whitney U test were used to compare the general clinical characteristics and thyroid function between the two groups. Spearman rank correlation analysis was performed to analyze the correlation between free thyroxine (FT 4), thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and fasting plasma glucose (FPG) in the first trimester as well as glucose levels in 75 g oral glucose tolerance test (OGTT). The associations between FT 4, TSH at different levels, and the detection rate of GDM, and the risk factors of GDM in twin pregnancies were analyzed using logistic regression. Results:(1) The prevalence of GDM in twin pregnancies was 25.0% (186/745). The positive rate of TPOAb was 13.6% (101/745). FPG in the first trimester was higher in the GDM group than that in the control [(4.7±0.5) vs (4.5±0.4) mmol/L, t=－5.08, P<0.001]. (2) No correlation between FT 4, TSH levels, the positive rate of TPOAb in the first trimester and FPG in the first trimester as well as OGTT results was found (all P>0.05). (3) There was no significant difference when using the thyroid function reference range for twin or singleton pregnancy in detecting hypothyroidism [0.5% (4/745) vs 0.4% (3/745)] and subclinical hypothyroidism [1.2% (9/745) vs 1.3% (10/745)] among the included subjects (both P>0.05), however, there were significant differences in the detection rates of hypothyroxinemia alone [25.0% (186/745) vs 12.9% (96/745)], hyperthyroidism [2.4% (18/745) vs 12.9% (96/745)] and subclinical hyperthyroidism [5.8% (43/745) vs 12.1% (90/745)]( χ2 were 35.43, 33.43 and 18.24, all P<0.001). There was no significant difference in the detection rate of thyroid disease between the GDM and control groups (all P>0.05). (4) FT 4 and TSH levels were grouped into quartiles ( Q1, Q2, Q3, and Q4), which showed that the detection rate of GDM was the highest [27.8% (52/187)] in women with FT 4 in Q1 and was the lowest [23.0% (43/187)] in those with FT 4 in Q2. However, the detection rate was the lowest in women with TSH in Q1 [24.1% (45/187)] and was the highest [27.4%(51/186)] in those with TSH in Q4. Taking Q1 of FT 4 and TSH as a reference, the logistic regression model showed that there were no statistically significant differences between FT 4, TSH at different levels, and GDM, even after adjusting for age, preconception-body mass index (pre-BMI), family history of diabetes, mode of conception, and chorionicity (all P>0.05). (5) Multivariate logistic regression analysis showed that maternal age ( OR=1.10, 95% CI: 1.05-1.15), pre-BMI ( OR=1.13, 95% CI: 1.07-1.21), family history of diabetes ( OR=2.73, 95% CI: 1.53-4.85), and FPG in the first trimester ( OR=2.14, 95% CI: 1.38-3.32) were independent risk factors for twin pregnancies complicated by GDM. Conclusions:Twin pregnant women with higher maternal age, pre-BMI, FPG in the first trimester and family history of diabetes were at higher risk of GDM. No significant correlation is found between maternal thyroid function in the first trimester and GDM in twin pregnancies.

Immunotherapy plays a compelling role in cancer treatment and has already made remarkable progress. However, many patients receiving immune checkpoint inhibitors fail to achieve clinical benefits, and the response rates vary among tumor types. New approaches that promote anti-tumor immunity have recently been developed, such as small molecules, bispecific antibodies, chimeric antigen receptor T cell products, and cancer vaccines. Small molecule drugs include agonists and inhibitors that can reach the intracellular or extracellular targets of immune cells participating in innate or adaptive immune pathways. Bispecific antibodies, which bind two different antigens or one antigen with two different epitopes, are of great interest. Chimeric antigen receptor T cell products and cancer vaccines have also been investigated. This review explores the recent progress and challenges of different forms of immunotherapy agents and provides an insight into future immunotherapeutic strategies.
Antibodies, Bispecific/therapeutic use* ; Cancer Vaccines ; Humans ; Immunotherapy ; Neoplasms/therapy* ; Receptors, Chimeric Antigen ; T-Lymphocytes

Toxoplasma gondii is an intracellular parasite that causes severe disease when the infection occurs during pregnancy. Adenosine is a purine nucleoside involved in numerous physiological processes; however, the role of adenosine receptors in T. gondii-induced trophoblast cell function has not been investigated until now. The goal of the present study was to evaluate the intracellular signaling pathways regulated by adenosine receptors using a HTR-8/SVneo trophoblast cell model of T. gondii infection. HTR8/SVneo human extravillous trophoblast cells were infected with or without T. gondii and then evaluated for cell morphology, intracellular proliferation of the parasite, adenosine receptor expression, TNF-α production and mitogen-activated protein (MAP) kinase signaling pathways triggered by adenosine A3 receptor (A3AR). HTR8/SVneo cells infected with T. gondii exhibited an altered cytoskeletal changes, an increased infection rate and reduced viability in an infection time-dependent manner. T. gondii significantly promoted increased TNF-α production, A3AR protein levels and p38, ERK1/2 and JNK phosphorylation compared to those observed in uninfected control cells. Moreover, the inhibition of A3AR by A3AR siRNA transfection apparently suppressed the T. gondii infection-mediated upregulation of TNF-α, A3AR production and MAPK activation. In addition, T. gondii-promoted TNF-α secretion was dramatically attenuated by pretreatment with PD098059 or SP600125. These results indicate that A3AR-mediated activation of ERK1/2 and JNK positively regulates TNF-α secretion in T. gondii-infected HTR8/SVneo cells.

Objective:To investigate expression level of transcriptional co-activator with PDZ-binding motif(TAZ) in neonatal rats with chronic lung diseases induced by hyperoxia and explore its potential role in the disease.Methods:The model of high-oxygen-induced lung injury in neonatal rats was established by continuous inhalation of high-concentration oxygen.The rats in experimental group inhaled 85% oxygen, while the rats in control group inhaled air.The lung tissues were collected at the 1st, 3rd, 7th, 14th and 21st day, and the lung tissue sections were stained with hematoxylin and eosin staining to observe the pathological changes of the lung.In addition, the dynamic expressions of TAZ, surfactant protein C(SPC) and aquaporin-5(AQP5) in lung tissue were detected by real-time PCR, western blot and immunohistochemistry staining.Results:In the experimental group, with the prolongation of oxygen inhalation time, we found that the alveolar cavity increased, the number decreased, the alveolar septum thickened, and the alveolar structure was simplified.Compared with the control group, there was no difference in TAZ, SPC and AQP5 expression at 1st and 3rd days in the lung tissue in the experimental group( P>0.05). However, at 7, 14 and 21 days, the expression of TAZ in mRNA and protein level in lung tissue in experimental group decreased significantly, and the expression of SPC in mRNA and protein level increased significantly, while the expression of AQP5 in mRNA and protein level decreased, the differences were all statistically significant( P<0.05). Conclusion:Hyperoxia can cause alveolar structure disorder and pulmonary arrested development in neonatal rat.The expression levels of SPC and AQP5 show that the injury of type Ⅰ alveolar epithelial cells (AEC Ⅰ) is severe.Although the number of type Ⅱ alveolar epithelial cells (AEC Ⅱ) increased, but its differentiation capacity decreased obviously.The decrease of TAZ expression may cause AEC Ⅱ lose the function of differentiation into AEC Ⅰ.