OBJECTIVE: To explore the prenatal and postnatal phenotypes of 22q11.2 microdeletion syndrome (22q11.2DS) and enhance clinical understanding of this condition. METHODS: Data were collected from 86 fetuses diagnosed with 22q11.2DS at four prenatal diagnostic centers across China between January 2014 and August 2025. Prenatal imaging findings, pregnancy outcomes, and postnatal conditions were analyzed. RESULTS: Among the 86 fetuses, complete ultrasound data were available for 65 cases. Cardiovascular abnormalities were observed in 42 cases, thymic hypoplasia or aplasia in 7 cases, urinary system anomalies in 6 cases, nuchal translucency (NT) thickening in 7 cases, butterfly vertebrae, clubfoot, omphalocele and diaphragmatic hernia in 1 case each, cleft lip and palate in 2 cases, and ultrasound soft markers in 13 cases. The parents of 9 fetuses opted to continue with the pregnancy. Among these, 6 showed no significant ultrasound abnormalities and no related phenotypes postnatally, while the remaining 3 exhibited ultrasound anomalies with postnatal manifestations including developmental delay, immunodeficiency, and cardiac defects. CONCLUSION Fetuses with 22q11.2DS may exhibit various ultrasound abnormalities in multiple systems before and after birth. In addition to cardiovascular anomalies, they may also present with thymic hypoplasia or aplasia, thickened NT, and urinary abnormalities. Fetuses with thickened NT or thymic anomalies should be closely monitored, and thymic assessment should be included in routine prenatal imaging evaluations. For fetuses with 22q11.2DS who show no ultrasound abnormalities, the risk of developing severe phenotypes after birth is relatively low, but occult palate clefts and psychiatric disorders cannot be ruled out. Due to limitations in sample size and follow-up duration, above conclusions require further validation through large-scale prospective studies.
Humans ; Female ; Pregnancy ; Ultrasonography, Prenatal ; DiGeorge Syndrome/genetics* ; Adult ; Male ; Follow-Up Studies ; Fetus/diagnostic imaging* ; Phenotype ; Infant, Newborn

OBJECTIVE: To explore the genotype-phenotype correlation in a Chinese family with structural brain abnormalities due to variant of the TUBB gene. METHODS: A family undergoing prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital in October 2024 was selected as the study subject. Clinical data were collected. Amniotic fluid sample was subjected to chromosomal copy number variation sequencing (CNV-seq). Trio whole-exome sequencing (Trio-WES) was carried out on the amniotic fluid and parental blood samples, and candidate variant was verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-KY-076-01). RESULTS: Both prenatal ultrasound and fetal MRI showed deviation of brain midline, unilateral lateral ventriculomegaly, and bilateral gyral asymmetry. Trio-WES revealed that the fetus has harbored a maternally derived heterozygous missense variant of the TUBB gene [NM_178014.4: c.155A>G (p.N52S)]. Sanger sequencing confirmed that the woman and a previously terminated fetus both harbored the same variant. Both the proband and two fetuses exhibited similar neuroimaging abnormalities including midline deviation and asymmetrical gyri. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+PS2_Moderate+PS3). CONCLUSION The heterozygous c.155A>G (p.N52S) variant was the TUBB gene probably underlay the pathogenesis of the structural brain abnormalities in this family. Above findings have expanded the phenotypic spectrum associated with the variant and facilitated the prenatal diagnosis for this family.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis ; Tubulin/genetics* ; Adult ; Brain/diagnostic imaging* ; Male ; Pedigree ; DNA Copy Number Variations/genetics* ; Exome Sequencing ; Genetic Association Studies ; Magnetic Resonance Imaging

OBJECTIVE: To investigate the genetic etiology of a fetus diagnosed with Mandibulofacial dysostosis with microcephaly (MFDM). METHODS: A fetus that underwent prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, on May 19, 2025 was selected for analysis. Results of fetal ultrasound findings, chromosomal karyotyping, copy number variation sequencing (CNV-seq), and whole-exome sequencing (WES) were collected. Sanger sequencing was performed for familial validation of the pathogenic variant. The Human Protein Atlas (HPA), STRING, and Simple ClinVar databases were queried to characterize the biological features of the candidate gene. Three-dimensional structures of the wild-type and variant proteins were modeled and analyzed, and the evolutionary conservation of the affected amino acid was assessed using UGENE. Prenatal phenotypes associated with EFTUD2 variants were summarized through a review of the literature. This study was approved by the Ethics Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (Ethics No.: 2025-KY-029-01). RESULTS: At 23⁺² weeks of gestation, ultrasound examination revealed bilateral microtia with low-set ears, mild micrognathia with a reduced mandibular-facial angle, a single umbilical artery, a slightly narrow aortic diameter, and trivial mitral regurgitation. Amniotic fluid karyotyping and CNV-seq showed no abnormalities. WES identified a de novo, previously unreported EFTUD2 variant, c.698dupA (p.V235Gfs*27), in the fetus. This frameshift variant is predicted to alter the structural integrity of the EFTUD2 protein. Literature review indicated that micrognathia and microtia or low-set ears are the most common sonographic features in fetuses with EFTUD2 variants, while secondary findings may include abnormal stomach bubble, cleft palate, single umbilical artery, gastrointestinal atresia, polyhydramnios, and reduced aortic diameter. CONCLUSION The EFTUD2: c.698dupA (p.V235Gfs*27) variant is likely the genetic cause underlying MFDM in this fetus.
Humans ; Mandibulofacial Dysostosis/diagnostic imaging* ; Microcephaly/diagnostic imaging* ; Female ; Pregnancy ; Ribonucleoprotein, U5 Small Nuclear/chemistry* ; Peptide Elongation Factors/chemistry* ; Fetus ; DNA Copy Number Variations/genetics* ; Adult ; Ultrasonography, Prenatal

BACKGROUND AND OBJECTIVES

The Philippines faces challenges in the screening of tuberculosis (TB), one of them being the shortage in the health workforce who are skilled and allowed to screen TB. Deep learning neural networks (DLNNs) have shown potential in the TB screening process utilizing chest radiographs (CXRs). However, local studies on AIbased TB screening are limited. This study evaluated qXR3.0 technology's diagnostic performance for TB screening in Filipino adults aged 15 and older. Specifically, we evaluated the specificity and sensitivity of qXR3.0 compared to radiologists' impressions and determined whether it meets the World Health Organization (WHO) standards.

A prospective cohort design was used to perform a study on comparing screening and diagnostic accuracies of qXR3.0 and two radiologist gradings in accordance with the Standards for Reporting Diagnostic Accuracy (STARD). Subjects from two clinics in Metro Manila which had qXR 3.0 seeking consultation at the time of study were invited to participate to have CXRs and sputum collected. Radiologists' and qXR3.0 readings and impressions were compared with respect to the reference standard Xpert MTB/RiF assay. Diagnostic accuracy measures were calculated.

With 82 participants, qXR3.0 demonstrated 100% sensitivity and 72.7% specificity with respect to the reference standard. There was a strong agreement between qXR3.0 and radiologists' readings as exhibited by the 0.7895 (between qXR 3.0 and CXRs read by at least one radiologist), 0.9362 (qXR 3.0 and CXRs read by both radiologists), and 0.9403 (qXR 3.0 and CXRs read as not suggestive of TB by at least one radiologist) concordance indices.

qXR3.0 demonstrated high sensitivity to identify presence of TB among patients, and meets the WHO standard of at least 70% specificity for detecting true TB infection. This shows an immense potential for the tool to supplement the shortage of radiologists for TB screening in the country. Future research directions may consider larger sample sizes to confirm these findings and explore the economic value of mainstream adoption of qXR 3.0 for TB screening.

OBJECTIVE: To elucidate how spinal manipulative therapy (SMT) exerts its analgesic effects through regulating brain function in lumbar disc herniation (LDH) patients by utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: From September 2021 to September 2023, we enrolled LDH patients (LDH group, n=31) and age- and sex-matched healthy controls (HCs, n=28). LDH group underwent rs-fMRI at 2 distinct time points (TPs): prior to the initiation of SMT (TP1) and subsequent to the completion of the SMT sessions (TP2). SMT was administered once every other day for 30 min per session, totally 14 treatment sessions over a span of 4 weeks. HCs did not receive SMT treatment and underwent only one fMRI scan. Additionally, participants in LDH group completed clinical questionnaires on pain using the Visual Analog Scale (VAS) and the Japanese Orthopedic Association (JOA) score, whereas HCs did not undergo clinical scale assessments. The effects on the brain were jointly characterized using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). Correlation analyses were conducted between specific brain regions and clinical scales. RESULTS: Following SMT treatment, pain symptoms in LDH patients were notably alleviated and accompanied by evident activation of effects in the brain. In comparison to TP1, TP2 exhibited the most significant increase in ALFF values for Temporal_Sup_R and the most notable decrease in ALFF values for Paracentral_Lobule_L (voxelwise P<0.005; clusters >30; FDR correction). Additionally, the most substantial enhancement in ReHo values was observed for the Cuneus_R, while the most prominent reduction was noted for the Olfactory_R (voxelwise P<0.005; clusters >30; FDR correction). Moreover, a comparative analysis revealed that, in contrast to HCs, LDH patients at TP1 exhibited the most significant increase in ALFF values for Temporal_Pole_Sup_L and the most notable decrease in ALFF values for Frontal_Mid_L (voxelwise P<0.005; clusters >30; FDR correction). Furthermore, the most significant enhancement in ReHo values was observed for Postcentral_L, while the most prominent reduction was identified for ParaHippocampal_L (voxelwise P<0.005; clusters >30; FDR correction). Notably, correlation analysis with clinical scales revealed a robust positive correlation between the Cuneus_R score and the rate of change in the VAS score (r=0.9333, P<0.0001). CONCLUSIONS Long-term chronic lower back pain in patients with LDH manifests significant activation of the "AUN-DMN-S1-SAN" neural circuitry. The visual network, represented by the Cuneus_R, is highly likely to be a key brain network in which the analgesic efficacy of SMT becomes effective in treating LDH patients. (Trial registration No. NCT06277739).
Humans ; Magnetic Resonance Imaging ; Intervertebral Disc Displacement/diagnostic imaging* ; Male ; Female ; Brain/diagnostic imaging* ; Adult ; Manipulation, Spinal/methods* ; Middle Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management ; Rest ; Case-Control Studies

OBJECTIVES: According to the World Health Organization (WHO), infertility rates have been steadily rising worldwide. Identifying risk factors for contrast agent reflux into the myometrium during hysterosalpingo-contrast sonography (HyCoSy) is of clinical significance in reducing this complication and improving infertility treatment. However, there is currently no standardized pre-evaluation method for predicting intra-myometrial contrast reflux, with clinical assessment often relying on physician experience and patient symptoms. This study aims to identify imaging risk factors for contrast agent reflux into the myometrium using four-dimensional (4D) HyCoSy and to construct a nomogram-based predictive model to assist in clinical decision-making. METHODS: A retrospective analysis was conducted on 1 274 infertile women who underwent 4D HyCoSy at the Women and Children's Hospital of Hunan and the the Third Xiangya Hospital of Central South University from January 1, 2020, to December 15, 2022. Patients were divided into a reflux group (n=234) and a non-reflux group (n=1 040) based on the presence of intra-myometrial contrast reflux. Univariate and multivariable Logistic regression analyses were used to identify significant predictors, which were then used to construct a nomogram model. Internal validation was performed using 500 bootstrap resamples. RESULTS: The age of the reflux group was significantly higher than that of the non-reflux group [(31.82±5.27) years vs (30.66±4.83) years, P=0.001 1]. Primary infertility was more common in the non-reflux group (50.96%), while secondary infertility dominated in the reflux group (76.50%), with 72.65% having a history of gynecological surgery (P<0.001). Abnormal menstrual volume and discomfort during the procedure were more common in the reflux group, while the non-reflux group tolerated higher contrast agent doses (P<0.001). Imaging differences included endometrial thickness, tubal wall smoothness, and peritoneal contrast dispersion, with the non-reflux group showing thicker endometrium and smoother, more patent tubes. The nomogram model yielded an area under the curve (AUC) of 0.854, indicating good predictive performance. The AUC of the decision curve analysis (DCA) for internal validation of the model was 0.737. When the threshold probability for contrast agent reflux into the myometrium ranged from 0.05 to 0.95, the maximum net benefit reached 0.18. The net benefit of applying the nomogram predictive model exceeded that of either full intervention or no intervention, indicating that the model demonstrates good clinical predictive performance. CONCLUSIONS The nomogram model, based on infertility type, endometrial thickness, contrast agent dose, and discomfort symptoms, effectively predicts intra-myometrial contrast agent reflux after 4D HyCoSy. It provides a valuable tool for clinicians to implement early preventive measures and reduce the risk of contrast leakage and associated complications.
Humans ; Female ; Nomograms ; Contrast Media/adverse effects* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Hysterosalpingography/methods* ; Infertility, Female/diagnostic imaging* ; Myometrium/diagnostic imaging* ; Risk Factors

OBJECTIVES: In recent years, the incidence and detection rate of pancreatic cystic lesions (PCLs) have increased significantly. Endoscopic ultrasound (EUS) plays an indispensable role in the diagnosis and differential diagnosis of PCLs. However, evidence comparing the diagnostic performance of EUS-guided fine-needle aspiration (EUS-FNA) and fine-needle biopsy (FNB) remains limited. This study aims to compare the diagnostic yield, adequacy of tissue acquisition, and safety between EUS-FNA and EUS-FNB in evaluating PCLs to inform clinical practice. METHODS: A retrospective review was conducted on patients with PCLs who underwent either EUS-FNA or EUS-FNB between January 2014 and August 2021. The diagnostic yield, tissue acquisition adequacy, and incidence of adverse events were compared between the 2 groups. RESULTS: A total of 90 patients with PCLs were included (52 in the FNA group and 38 in the FNB group). The diagnostic yield was similar between the FNA and FNB groups (94.2% vs 94.7%, P>0.05). The adequacy of tissue acquisition was 71.2% in the FNA group and 81.6% in the FNB group (P>0.05). No statistically significant difference was observed in the incidence of adverse events between the 2 groups (P>0.05). CONCLUSIONS Both EUS-FNA and EUS-FNB demonstrate equally high diagnostic yields and tissue adequacy in PCLs, with excellent safety profiles. Both methods are safe and effective diagnostic tools for evaluating PCLs.
Humans ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/adverse effects* ; Retrospective Studies ; Female ; Male ; Pancreatic Cyst/diagnostic imaging* ; Middle Aged ; Biopsy, Fine-Needle/adverse effects* ; Aged ; Pancreatic Neoplasms/diagnosis* ; Adult ; Endosonography/methods* ; Pancreas/pathology* ; Diagnosis, Differential

Premenstrual dysphoric disorder (PMDD) is considered a severe form of premenstrual syndrome (PMS). As a key brain region involved in emotional regulation and stress responses, the amygdala has been implicated in the pathogenesis of PMS/PMDD. The amygdala is composed of multiple subregions, each playing distinct roles in emotion, memory, and stress responses, and forms complex brain areas. Summarizing the interconnections among amygdala, subregions and their connectivity with external areas, and exploringt the neuroimaging characteristics of the amygdala, as well as changes in its neural circuits and brain networks in these patients, will help provide a theoretical foundation for targeted modulation of amygdala function in the treatment of PMS/PMDD.
Humans ; Amygdala/diagnostic imaging* ; Female ; Premenstrual Dysphoric Disorder/pathology* ; Premenstrual Syndrome/pathology* ; Emotions/physiology* ; Magnetic Resonance Imaging

OBJECTIVES: Renal cell carcinoma (RCC) is a malignant renal tumor that poses a significant threat to patient health. Accurate preoperative pathological grading plays a crucial role in determining the appropriate treatment for this disease. Currently, deep learning technology has become an important method for pathological grading of RCC. However, existing methods primarily rely on single-phase computed tomography (CT) imaging for analysis and prediction, which has limitations such as missing small lesions, one-sided evaluation, and local focusing issues. Therefore, this study proposes a multi-modal deep learning algorithm that integrates multi-phase enhanced CT images with clinical variable data, aiming to provide a basis for predicting the pathological grading of RCC. METHODS: First, the algorithm took four-phase enhanced CT images from the plain scan, arterial phase, venous phase, and delayed phase, along with clinical variables, as inputs. Then, an embedding encoding module was used to extract heterogeneous information from the clinical variables, and a 3-dimensional (3D) ResNet50 model was employed to capture spatial information from the multi-phase enhanced CT image data. Finally, a Fusion module deeply integrated the feature information from clinical variables and each phase's CT image features, further utilizing a cross-self-attention mechanism to achieve multi-phase feature fusion. This approach comprehensively captures the deep semantic information from the patient data, fully leveraging the complementary advantages of multi-modal and multi-phase data. To validate the effectiveness of the proposed method, a total of 1 229 RCC patients were approved by ethics review were included to train the model. RESULTS: Experimental results demonstrated superior performance compared to traditional radiomics and state-of-the-art deep learning methods, achieving an accuracy of 83.87%, a recall rate of 95.04%, and an F1-score of 82.23%. CONCLUSIONS The proposed algorithm exhibits strong stability and sensitivity, significantly enhancing the predictive performance of RCC pathological grading. It offers a novel approach for accurate RCC diagnosis and personalized treatment planning.
Humans ; Carcinoma, Renal Cell/pathology* ; Deep Learning ; Kidney Neoplasms/diagnostic imaging* ; Tomography, X-Ray Computed/methods* ; Algorithms ; Neoplasm Grading ; Male ; Female ; Middle Aged

OBJECTIVES: In recent years, the role of remnant cholesterol (RC) in the development and progression of cardiovascular diseases has gained increasing attention. However, evidence on the association between RC and subclinical atherosclerosis is limited. This study aims to examine the relationship between RC and atherosclerotic plaques in single and multiple vascular territories. METHODS: This retrospective cross-sectional study used baseline data from participants enrolled between October 2022 and May 2024 in the National Key Research Program "Study on the Prevention and Control System of Risk Factors for Panvascular Diseases". Color Doppler ultrasonography was performed to detect plaques in 4 vascular territories: Bilateral carotid arteries, bilateral subclavian arteries, abdominal aorta, and iliac-femoral arteries. RC was calculated as total cholesterol minus the sum of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Participants were categorized into quartiles (Q1-Q4) according to RC levels. The proportions of participants with ≥2 plaques in a single vascular territory and with plaques in ≥2 vascular territories were compared across RC quartiles. Multivariate ordinal Logistic regression was used to assess the association between RC and the number of plaques in a single vascular territory, as well as the risk of multiple vascular territory involvement. Additionally, the effects of LDL-C/RC concordance on plaque distribution were analyzed. RESULTS: A total of 3 539 participants were included, of whom 2 169 (61.29%) were male, with a age of (51.94±9.22) years. From Q1 to Q4, the proportion of participants with ≥2 plaques in a single vascular territory (bilateral carotid, subclavian, abdominal aorta, and iliac-femoral arteries), as well as those with plaques in ≥2 vascular territories, increased progressively. Compared with Q1, both Q3 and Q4 were significantly associated with higher plaque numbers in a single vascular territory (both P<0.05). When treated as a continuous variable, higher RC levels were associated with an increased risk of greater plaque numbers within a single vascular territory (all P<0.05). RC levels were also significantly associated with multiple vascular territory involvement: Compared with Q1, Q4 had a 1.015-fold higher risk [odds ratio (OR)=2.015, 95% confidence interval (CI) 1.669 to 2.433], and each 1 mmol/L increase in RC corresponded to a 0.160-fold increased risk (OR=1.160, 95% CI 1.073 to 1.271). In LDL-C/RC coordination analysis, compared with the low LDL-C/low RC group, the low LDL-C/high RC group was significantly associated with multiple vascular territory involvement (OR=1.576, 95% CI 1.220 to 2.036). CONCLUSIONS Elevated RC levels are closely associated with atherosclerotic plaques in both single and multiple vascular territories, even among individuals with normal LDL-C, suggesting that RC should be considered in clinical risk assessment and management of atherosclerosis.
Humans ; Plaque, Atherosclerotic/diagnostic imaging* ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Retrospective Studies ; Cholesterol/blood* ; Cholesterol, LDL/blood* ; Aged ; Cholesterol, HDL/blood* ; Risk Factors ; Atherosclerosis ; Ultrasonography, Doppler, Color ; Femoral Artery/diagnostic imaging*