Latest progress in low-intensity pulsed ultrasound for studying exosomes derived from stem/progenitor cells.

Stem cells have self-renewal, replication, and multidirectional differentiation potential, while progenitor cells are undifferentiated, pluripotent or specialized stem cells. Stem/progenitor cells secrete various factors, such as cytokines, exosomes, non-coding RNAs, and proteins, and have a wide range of applications in regenerative medicine. However, therapies based on stem cells and their secreted exosomes present limitations, such as insufficient source materials, mature differentiation, and low transplantation success rates, and methods addressing these problems are urgently required. Ultrasound is gaining increasing attention as an emerging technology. Low-intensity pulsed ultrasound (LIPUS) has mechanical, thermal, and cavitation effects and produces vibrational stimuli that can lead to a series of biochemical changes in organs, tissues, and cells, such as the release of extracellular bodies, cytokines, and other signals. These changes can alter the cellular microenvironment and affect biological behaviors, such as cell differentiation and proliferation. Here, we discuss the effects of LIPUS on the biological functions of stem/progenitor cells, exosomes, and non-coding RNAs, alterations involved in related pathways, various emerging applications, and future perspectives. We review the roles and mechanisms of LIPUS in stem/progenitor cells and exosomes with the aim of providing a deeper understanding of LIPUS and promoting research and development in this field.

Different subtypes of ultrasound-diagnosed adenomyosis and in vitro fertilization outcomes: A systematic review and meta-analysis.

INTRODUCTION: Adenomyosis prevalence among women with infertility is increasing; their management during in vitro fertilization is usually based on ultrasound diagnosis alone. Herein, we summarize the latest evidence on the impact of ultrasound-diagnosed adenomyosis on in vitro fertilization outcomes. MATERIAL AND METHODS: The study was registered with The International Prospective Register of Systematic Reviews (CRD42022355584). We searched PubMed, Embase, and Cochrane Library databases from inception to January 31, 2023, for cohort studies on the impact of adenomyosis on in vitro fertilization outcomes. Fertility outcomes were compared according to the presence of adenomyosis as diagnosed by ultrasound, concurrent endometriosis and adenomyosis, and MRI-based or MRI- and ultrasound-based adenomyosis diagnosis. Live birth rate was the primary outcome while clinical pregnancy and miscarriage rates were secondary outcomes. RESULTS: Women diagnosed with adenomyosis by ultrasound had lower live birth (odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.53-0.82, grade: very low), lower clinical pregnancy (OR = 0.64; 95% CI: 0.53-0.77, grade: very low), and higher miscarriage (OR = 1.81; 95% CI: 1.35-2.44, grade: very low) rates than those without adenomyosis. Notably, symptomatic and diffuse, but not asymptomatic adenomyosis as diagnosed by ultrasound, adversely affected in vitro fertilization outcomes, with lower live birth (OR = 0.57; 95% CI: 0.34-0.96, grade: very low), clinical pregnancy (OR = 0.69; 95% CI: 0.57-0.85, grade: low), and miscarriage (OR = 2.48, 95% CI: 1.28-4.82, grade: low) rates; and lower live birth (OR = 0.37; 95% CI: 0.23-0.59, grade: low) and clinical pregnancy (OR = 0.50; 95% CI: 0.34-0.75, grade: low), but not miscarriage rate (OR = 2.18; 95% CI: 0.72-6.62, grade: very low), respectively. Concurrent adenomyosis in endometriosis is associated with a significantly lower live birth rate (OR = 0.44; 95% CI: 0.26-0.75, grade: low) than endometriosis alone. Finally, the use of MRI-based or MRI- and ultrasound-based adenomyosis diagnosis showed no significant association with in vitro fertilization outcomes (grade: very low for all outcomes). CONCLUSIONS: Considering ultrasound findings, symptoms, and different subtypes of adenomyosis may aid in offering personalized counseling, improving treatment decisions, and achieving better outcomes of in vitro fertilization.

Advances in the clinical application of ultrasound elastography in uterine imaging.

Changes in tissue stiffness by physiological or pathological factors in tissue structure are identified earlier than their clinical features. Pathological processes such as uterine fibrosis, adenomyosis, endometrial lesions, infertility, and premature birth can manifest as tissue elasticity changes. In clinical settings, elastography techniques based on ultrasonography, optical coherence tomography, and magnetic resonance imaging are widely used for noninvasive measurement of mechanical properties in patients, providing valuable tool and information for diagnosis and treatment. Ultrasound elastography (USE) plays a critical role in obstetrics and gynecology clinical work because of its simplicity, non-invasiveness, and repeatability. This article reviews the recent progress of USE in uterine tumor diagnosis (especially early diagnosis and treatment effect evaluation), prediction of preterm birth, and intrauterine insemination. We believe that USE, especially shear wave elastography, may serve as a potential means to assess tissue stiffness, thereby improving the diagnosis and treatment of adenomyosis, fibroids, endometrial lesions, cervical cancer, and precise management of preterm birth and intrauterine insemination monitoring.

Comparison of O-RADS, GI-RADS, and ADNEX for Diagnosis of Adnexal Masses: An External Validation Study Conducted by Junior Sonologists.

OBJECTIVE: To externally validate the Ovarian-adnexal Reporting and Data System (O-RADS) and evaluate its performance in differentiating benign from malignant adnexal masses (AMs) compared with the Gynecologic Imaging Reporting and Data System (GI-RADS) and Assessment of Different NEoplasias in the adneXa (ADNEX). METHODS: A retrospective analysis was performed on 734 cases from the Second Affiliated Hospital of Fujian Medical University. All patients underwent transvaginal or transabdominal ultrasound examination. Pathological diagnoses were obtained for all the included AMs. O-RADS, GI-RADS, and ADNEX were used to evaluate AMs by two sonologists, and the diagnostic efficacy of the three systems was analyzed and compared using pathology as the gold standard. We used the kappa index to evaluate the inter-reviewer agreement (IRA). RESULTS: A total of 734 AMs, including 564 benign masses, 69 borderline masses, and 101 malignant masses were included in this study. O-RADS (0.88) and GI-RADS (0.90) had lower sensitivity than ADNEX (0.95) (P < .05), and the PPV of O-RADS (0.98) was higher than that of ADNEX (0.96) (P < .05). These three systems showed good IRA. CONCLUSION: O-RADS, GI-RADS, and ADNEX showed little difference in diagnostic performance among resident sonologists. These three systems have their own characteristics and can be selected according to the type of center, access to patients' clinical data, or personal comfort.

The effect of ultrasound-guided intraperitoneal injection of ulinastatin on lung development in intrauterine growth-restricted fetal rabbits.

OBJECTIVES: To investigate the effect and mechanism of ulinastatin (UTI) on development of lungs in fetal rabbits with intrauterine growth retardation (IUGR). METHODS: Twenty pregnant rabbits were equally divided into normal, IUGR, UTI, and LY groups. The normal group was only injected with saline and marked with tattoo ink. IUGR models were established by injecting N-nitro-L-arginine methyl ester in the rabbits of IUGR, UTI, and LY groups. The three groups were injected with saline, UTI, or UTI + LY294002 (PI3K inhibitor) respectively, and then marked with tattoo ink. After cesarean section, neonatal weights, and levels of dipalmitoyl phosphatidylcholine (DPPC), nitric oxide (NO), P-Akt, P-eNOS, and pulmonary surfactant-associated protein A (SP-A) were determined in tissues of the lungs. Radial alveoli count (RAC), pulmonary interstitial ratio, and ultrastructural changes in type II alveolar epithelial cells (AEC II) were also determined through light and electron microscopy. RESULTS: Compared with control, the IUGR group showed significantly decreased weight, RAC, lamellar bodies in AEC II, and levels of P-Akt, P-eNOS, DPPC, NO, and SP-A, and increased pulmonary interstitial ratio (p < .05). The UTI treatment did not affect the weight; however, all other parameters were opposite to those observed in the IUGR group (p < .05). Furthermore, these UTI-mediated changes were inhibited by LY294002. CONCLUSIONS: Intraperitoneal UTI injection can promote the development of lungs and increase pulmonary surfactant production in IUGR fetal rabbits, potentially by activating PI3K/Akt/eNOS/NO signaling.

Assessment of liver fibrosis with liver and spleen stiffness measured by sound touch elastography, serum fibrosis markers in patients with chronic hepatitis B.

OBJECTIVES: To evaluate the performance of liver stiffness (LS) and spleen stiffness (SS) by using the sound touch elastography (STE) technique and compare with those of the splenic index, aspartate transaminase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) index, King's score and combined models for diagnosing and staging fibrosis in chronic hepatitis B (CHB). METHODS: One hundred patients with CHB underwent STE and serological tests. LS and SS values were measured with STE technique, and splenic index was calculated. Staging of fibrosis was determined with liver biopsy. Correlations between the individual parameters and the stage of fibrosis were evaluated with the Spearman correlation analysis. The area under the receiver operating characteristic curve (AUROC) was calculated to analyze the performance of all methods. RESULTS: Among all individual parameters, LS showed the highest AUROC for diagnosing fibrosis of ≥S2, ≥S3, and S4 stages (AUROC: 0.70, 0.86, and 0.96, respectively; all P < 0.05). The AUROC of combined model 1 (LS and SS) and 2 (LS, SS, APRI, FIB-4 index, King's score) for diagnosing ≥S2, ≥S3, and S4 fibrosis were 0.70, 0.86, 0.97, and 0.70, 0.86, 0.96, respectively, which were higher than those of APRI, FIB-4 index and the King's score (P < 0.05). No significant differences were found between two combined models and LS for staging fibrosis (P > 0.05). CONCLUSIONS: LS measurement is reliable for diagnosing and staging fibrosis in CHB, with a better performance than SS, splenic index and serum biomarkers. It is also comparable with the performance of combined models.

Maternal nicotine exposure aggravates metabolic associated fatty liver disease via PI3K/Akt signaling in adult offspring mice.

AIM: The aim of this study is to investigate the effect of maternal nicotine exposure (MNE) on the development of metabolic associated fatty liver disease (MAFLD) in adulthood offspring and the underlying mechanism. METHODS: Pregnant mice (n = 22) were subcutaneously injected with either saline vehicle (n = 11) or nicotine (n = 11) twice a day on gestational days 11-21. Offspring mice (n = 176) from both groups were weaned at postnatal day 21, and for 6 months after postnatal day 21, 96 mice were fed either a standard chow diet (n = 48) or a high-fat diet (n = 48). Serum lipid indicators, liver function indicators, insulin, and liver mitochondrial respiration were analyzed. The expression levels of fibrosis-related proteins, phosphorylated PI3K, phosphorylated Akt, sterol regulatory element-binding transcription factor 1 (SREBP1c), and peroxisome proliferator-activated receptor alpha (PPAR-α) were detected in the liver by immunohistochemistry and Western blotting. RESULTS: MNE significantly decreased the weight of both maternal and offspring mice (~30%) and inhibited organ growth in offspring mice (P < .05). MNE also significantly increased serum levels of total bile acid, triglycerides, total cholesterol, glucose, alanine aminotransferase, aspartate aminotransferase, low-density lipoprotein, and insulin while decreasing serum high-density lipoprotein levels and mitochondrial respiration activity in mice fed either the normal diet or high-fat diet (all P < .05). These effects of MNE on lipid metabolism and insulin resistance were mediated via PI3K and Akt phosphorylation and down-regulation of SREBP1c and PPAR-α. CONCLUSION: Our data indicate MNE induces lipid metabolism disorder and insulin resistance to promote MAFLD progression in adult offspring through activation of PI3K/Akt signaling and suppression of SREBP1c and PPARα protein expression.

Diagnostic Performance of Ultrasound Computer-Aided Diagnosis Software Compared with That of Radiologists with Different Levels of Expertise for Thyroid Malignancy: A Multicenter Prospective Study.

The aim of the work described here was to evaluate the diagnostic performance of ultrasound thyroid computer-aided diagnosis (CAD) software. This multicenter prospective study included 494 patients (565 thyroid nodules) who underwent surgery or biopsy after ultrasonography at four hospitals from January 2019 to September 2019. The diagnostic performance metrics of different readers were calculated and compared with the pathologic results. The sensitivity of CAD was outstanding and was equivalent to that of a senior radiologist (90.51% vs. 88.47%, p > 0.05). The area under the curve of CAD was equivalent to that of a junior radiologist (0.748 vs. 0.739, p > 0.05). However, the specificity was only 49.63%, which was lower than those of the three radiologists (75.56%, 85.93% and 90.37% for the junior, intermediate and senior radiologists, respectively). The diagnostic performance of the junior radiologist was significantly improved with the aid of CAD (junior + CAD). The sensitivity and area under the curve of junior + CAD were improved from 72.20% to 89.93% and from 0.739 to 0.816, respectively (both p values <0.05), and the positive predictive value, negative predictive value and κ coefficient improved from 76.3% to 78.6%, 82.0% to 86.8% and 0.394 to 0.511, respectively. Though specificity slightly decreased from 75.56% to 73.33%, the difference was not statistically significant (p > 0.05). In general, the clinical application value of CAD is promising, and its instrumental value for junior radiologists is significant.

[The effects of prenatal radiation of mobile phones on white matter in cerebellum of rat offspring].

OBJECTIVE: To evaluate the effects of prenatal radiation of 850～1 900 MHz mobile phone on white matter in cerebellum of adult rat offspring. METHODS: Pregnant rats were randomly divided into short term maternal radiation group, long term maternal radiation group and control group. Rats in short term and long term maternal radiation group were exposed to 6 h/d and 24 h/d mobile phone radiation during 1-17 days of pregnancy, respectively. The cerebellums of offspring rats at the age of 3 month(n＝8)were taken. Cell morphology in cerebellum was studied by hematoxylin-eosin (HE) staining. The expressions of myelin basic protein (MBP), neurofilament-L (NF-L) and glial fibrillary acidic protein (GFAP) in cerebellum of rat offspring were detected by immunohistochemistry and Western blot. RESULTS: Compared to control group, the morphological changes of purkinje cells in cerebellum were obvious in rat offspring of short term and long term maternal radiation group. Compared to control group, decreased MBP and NF-L expressions and increased GFAP expression were observed in long term maternal radiation group(all P＜0.05). Compared to short term radiation group, the expressions of MBP and NF-L were down-regulated (all P＜0.05) and the expression of GFAP was up- regulated(P＜0.05) in long term radiation group. CONCLUSION: Prenatal mobile phone radiation might lead to the damage of myelin and axon with activity of astrocytes in cerebellum of male rat offspring, which is related to the extent of radiation.

Sonographic Features of Cervical Lymph Nodes in Patients With Hashimoto Thyroiditis and the Impacts From the Levothyroxine With Prednisone Therapy.

OBJECTIVE: This study aimed to evaluate the ultrasonographic pattern of cervical lymph nodes (CLNs) and whether levothyroxine with prednisone therapy is effective for lymphadenopathy in patients with Hashimoto thyroiditis (HT). METHODS: This retrospective study was looking at patients with confirmed diagnosis of HT who underwent comprehensive neck ultrasound examination. We reviewed sonographic findings in 127 patients with HT, 234 euthyroid patients with goiter, and 122 healthy subjects. In addition, 30 untreated HT patients with cervical lymphadenopathy were recruited for the levothyroxine with prednisone therapy. We rescanned the patients 9 months after treatment with levothyroxine and prednisone. RESULTS: Patients with HT had a higher rate of CLN detection on ultrasound than euthyroid patients with goiter and healthy subjects at cervical levels III, IV, and VI (P < 0.01). In addition, patients with HT had a higher rate of detection of CLNs with abnormal sonographic features than the other 2 groups, most notably at cervical levels III, IV, and VI (P < 0.01). After the treatment, the mean thyroid volume, thyroid nodule volume, CLN volume, symptom score, and cosmetic grade of 30 HT patients were remarkably decreased (P < 0.01 or P < 0.001). CONCLUSIONS: Hashimoto thyroiditis seems to be associated with an increased rate of detection of CLNs with abnormal sonographic features, particularly at cervical levels III, IV, and VI. Therapy with levothyroxine with prednisone is effective for cervical lymphadenopathy in patients with HT.