How to identify juxtaglomerular cell tumor by ultrasound: a case series and review of the literature.

PURPOSE: To study the value of ultrasound in the diagnosis of juxtaglomerular cell tumor (JGCT). METHODS: From January 2005 to July 2020, fifteen patients diagnosed as JGCT by surgical pathology in Peking Union Medical College Hospital were collected. All patients underwent preoperative ultrasound examination. The clinical, laboratory, ultrasound, computed tomography (CT), surgical, and pathological features of the patients were analyzed retrospectively. RESULTS: The 15 patients were 5 males and 10 females with a median age of 29 years (10∼72 years). 14 of them had hypertension and one had normal blood pressure. The tumors were all solitary, with a median diameter of 1.5 cm (0.9-5.9 cm). Among the fifteen patients, eleven were correctly detected by preoperative ultrasound, and four were missed. There was a significant difference in tumor size (2.64 ± 1.48 cm vs. 1.23 ± 0.21 cm) and whether the tumor protruded outward (9/11 vs. 0/4) between the ultrasound-detected group and the ultrasound-missed group (p = 0.010, p = 0.011). Of the 11 tumors detected by ultrasound, four were extremely hypoechoic, two were hypoechoic, three were isoechoic, and two were hyperechoic. Color Doppler showed no blood flow in five tumors with the size range from 0.9 to 2.0 cm, and mild blood flow in six tumors with the size range from 2.8 to 5.9 cm. CONCLUSIONS: JGCT is rare, and has characteristic clinical manifestations. Diagnosis should be suspected in case of secondary hypertension, particularly in young women, if no renal vascular cause was found. Ultrasound, combined with clinical manifestations, was helpful for the diagnosis.

A Retrospective Study of Ultrasonography in the Investigation of Primary Hyperparathyroidism: A New Perspective for Ultrasound Echogenicity Features of Parathyroid Nodules.

OBJECTIVE: To identify and understand parathyroid lesions of patients with primary hyperparathyroidism (PHPT) more accurately under ultrasound. METHODS: This retrospective study involved 423 adult patients with PHPT with a single parathyroid nodule and positive parathyroid ultrasonography between 2018 and 2019. The clinical characteristics of the study patients and histopathologic sections were reviewed. RESULTS: According to the main grayscale echogenicity features of parathyroid nodules, 423 cases were divided into groups: iso-hyperechogenicity solid (61/423), hypoechogenicity solid (304/423), and mixed-echogenicity cyst-solid (58/423) groups. Comparison among the 3 groups showed that the iso-hyperechogenicity group included more asymptomatic patients with PHPT and fewer patients with severe symptoms like bone fractures (P < .05). The mixed-echogenicity group showed higher median serum parathyroid hormone (PTH) and serum calcium levels and larger lesion sizes (P < .05), and the iso-hyperechogenicity group showed the lowest median serum PTH level. No difference in lesion size was noted between the 2 solid groups, but the median serum PTH level in the hypoechogenicity group was higher than that in the iso-hyperechogenicity group (P < .05). According to histopathology, the hypoechogenic area of the samples may contain more functional components (chief cells), whereas the iso-hyperechogenic area has more nonfunctional components (eg, lipocytes and connective tissues). CONCLUSION: The PHPT nodules distinguished by ultrasound echogenicity features showed different histopathologic components, reflected by different clinical characteristics of the patients with PHPT.

Fetal weight estimation by automated three-dimensional limb volume model in late third trimester compared to two-dimensional model: a cross-sectional prospective observational study.

BACKGROUND: Accurate estimation of fetal weight is important for prenatal care and for detection of fetal growth abnormalities. Prediction of fetal weight entails the indirect measurement of fetal biometry by ultrasound that is then introduced into formulae to calculate the estimated fetal weight. The aim of our study was to evaluate the accuracy of fetal weight estimation of Chinese fetuses in the third trimester using an automated three-dimensional (3D) fractional limb volume model, and to compare this model with the traditional two-dimensional (2D) model. METHODS: Prospective 2D and 3D ultrasonography were performed among women with singleton pregnancies 7 days before delivery to obtain 2D data, including fetal biparietal diameter, abdominal circumference and femur length, as well as 3D data, including the fractional arm volume (AVol) and fractional thigh volume (TVol). The fetal weight was estimated using the 2D model and the 3D fractional limb volume model respectively. Percentage error was defined as (estimated fetal weight - actual birth weight) divided by actual birth weight and multiplied by 100. Systematic errors (accuracy) were evaluated as the mean percentage error (MPE). Random errors (precision) were calculated as ±1 SD of percentage error. The intraclass correlation coefficient (ICC) was used to analyze the inter-observer reliability of the 3D ultrasound measurements of fractional limb volume. RESULTS: Ultrasound examination was performed on 56 fetuses at 39.6 ± 1.4 weeks' gestation. The average birth weight of the newborns was 3393 ± 530 g. The average fetal weight estimated by the 2D model was 3478 ± 467 g, and the MPE was 3.2 ± 8.9. The average fetal weights estimated by AVol and TVol of the 3D model were 3268 ± 467 g and 3250 ± 485 g, respectively, and the MPEs were - 3.3 ± 6.6 and - 3.9 ± 6.1, respectively. For the 3D TVol model, the proportion of fetuses with estimated error ≤ 5% was significantly higher than that of the 2D model (55.4% vs. 33.9%, p < 0.05). For fetuses with a birth weight < 3500 g, the accuracy of the AVol and TVol models were better than the 2D model (- 0.8 vs. 7.0 and - 2.8 vs. 7.0, both p < 0.05). Moreover, for these fetuses, the proportions of estimated error ≤ 5% of the AVol and TVol models were 58.1 and 64.5%, respectively, significantly higher than that of the 2D model (19.4%) (both p < 0.05). The inter-observer reliability of measuring fetal AVol and TVol were high, with the ICCs of 0.921 and 0.963, respectively. CONCLUSION: In this cohort, the automated 3D fractional limb volume model improves the accuracy of weight estimation in most third-trimester fetuses. Prediction accuracy of the 3D model for neonatal BW, particularly < 3500 g was higher than that of the traditional 2D model.

The multiple reference range of mean uterine artery pulsatility index for natural and in vitro fertilization singletons during 11-14 gestational weeks.

Background: Ultrasonography of the uterine artery (UtA) in the first and second trimesters of pregnancy can assess uterine-placental blood perfusion and guide early clinical prevention. Establishing normal ranges of the UtA pulsatility index (UtA-PI) at 11-14 weeks of pregnancy is helpful for the early identification of high-risk pregnant women and improving the prognosis. This study aimed to establish a reference range of UtA-PI based on crown-rump length (CRL) for spontaneous and in vitro fertilization (IVF) singleton pregnancy during 11-14 weeks, respectively. Methods: A prospective study was performed at Peking Union Medical College Hospital. Healthy, low-risk women with a singleton pregnancy at 11-14 gestational weeks were consecutively recruited for this study from December 2017 to December 2020. All participants underwent routine prenatal ultrasound examination. The CRL of the fetus and the UtA-PI were measured in both uterine arteries, and average values were calculated. The LMS method was used to fit the percentile (P)5, P10, P25, P50, P75, P90, and P95 curves of the UtA-PI value of spontaneous and IVF singleton pregnancy with CRL changes, respectively. Results: A total of 1,962 pregnant women with normal fetuses were included in this study, including 1,792 pregnancies conceived naturally and 170 IVF fetuses. The UtA-PI reference range in the spontaneous pregnancy group was consistently higher than that in the IVF group during 11-14 weeks, and showed a statistically significant difference in UtA-PI for spontaneous and IVF pregnancies (P<0.001). According to the LMS method, each percentile curve of UtA-PI decreased with the increase of CRL in both the natural pregnancy group and the IVF group. The P95 range of UtA-PI for pregnant women with naturally conceived and IVF pregnancy was 2.74 to 2.11 and 2.50 to 1.94, respectively. The overall change of UtA-PI differentials of the two groups showed a downward trend and decreased slightly with the increase of CRL. Conclusions: This study provided a single-center, large sample of data and constructed a CRL-based reference value of UtA-PI for spontaneous and IVF singleton pregnancy, which provides a reliable basis for early UtA evaluation and early clinical decision-making during 11-14 gestational weeks.

Diagnostic Value of Breast Lesions Between Deep Learning-Based Computer-Aided Diagnosis System and Experienced Radiologists: Comparison the Performance Between Symptomatic and Asymptomatic Patients.

Purpose: The purpose of this study was to compare the diagnostic performance of breast lesions between deep learning-based computer-aided diagnosis (deep learning-based CAD) system and experienced radiologists and to compare the performance between symptomatic and asymptomatic patients. Methods: From January to December 2018, a total of 451 breast lesions in 389 consecutive patients were examined (mean age 46.86 ± 13.03 years, range 19-84 years) by both ultrasound and deep learning-based CAD system, all of which were biopsied, and the pathological results were obtained. The lesions were diagnosed by two experienced radiologists according to the fifth edition Breast Imaging Reporting and Data System (BI-RADS). The final deep learning-based CAD assessments were dichotomized as possibly benign or possibly malignant. The diagnostic performances of the radiologists and deep learning-based CAD were calculated and compared for asymptomatic patients and symptomatic patients. Results: There were 206 asymptomatic screening patients with 235 lesions (mean age 45.06 ± 10.90 years, range 21-73 years) and 183 symptomatic patients with 216 lesions (mean age 50.03 ± 14.97 years, range 19-84 years). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and area under the receiver operating characteristic curve (AUC) of the deep learning-based CAD in asymptomatic patients were 93.8, 83.9, 75.0, 96.3, 87.2, and 0.89%, respectively. In asymptomatic patients, the specificity (83.9 vs. 66.5%, p < 0.001), PPV (75.0 vs. 59.4%, p = 0.013), accuracy (87.2 vs. 76.2%, p = 0.002) and AUC (0.89 to 0.81, p = 0.0013) of CAD were all significantly higher than those of the experienced radiologists. The sensitivity (93.8 vs. 80.0%), specificity (83.9 vs. 61.8%,), accuracy (87.2 vs. 73.6%) and AUC (0.89 vs. 0.71) of CAD were all higher for asymptomatic patients than for symptomatic patients. If the BI-RADS 4a lesions diagnosed by the radiologists in asymptomatic patients were downgraded to BI-RADS 3 according to the CAD, then 54.8% (23/42) of the lesions would avoid biopsy without missing the malignancy. Conclusion: The deep learning-based CAD system had better performance in asymptomatic patients than in symptomatic patients and could be a promising complementary tool to ultrasound for increasing diagnostic specificity and avoiding unnecessary biopsies in asymptomatic screening patients.

Simultaneous Detection of CNVs and SNVs Improves the Diagnostic Yield of Fetuses with Ultrasound Anomalies and Normal Karyotypes.

The routine assessment to determine the genetic etiology for fetal ultrasound anomalies follows a sequential approach, which usually takes about 6-8 weeks turnaround time (TAT). We evaluated the clinical utility of simultaneous detection of copy number variations (CNVs) and single nucleotide variants (SNVs)/small insertion-deletions (indels) in fetuses with a normal karyotype with ultrasound anomalies. We performed CNV detection by chromosomal microarray analysis (CMA) or low pass CNV-sequencing (CNV-seq), and in parallel SNVs/indels detection by trio-based clinical exome sequencing (CES) or whole exome sequencing (WES). Eight-three singleton pregnancies with a normal fetal karyotype were enrolled in this prospective observational study. Pathogenic or likely pathogenic variations were identified in 30 cases (CNVs in 3 cases, SNVs/indels in 27 cases), indicating an overall molecular diagnostic rate of 36.1% (30/83). Two cases had both a CNV of uncertain significance (VOUS) and likely pathogenic SNV, and one case carried both a VOUS CNV and an SNV. We demonstrated that simultaneous analysis of CNVs and SNVs/indels can improve the diagnostic yield of prenatal diagnosis with shortened reporting time, namely, 2-3 weeks. Due to the relatively long TAT for sequential procedure for prenatal genetic diagnosis, as well as recent sequencing technology advancements, it is clinically necessary to consider the simultaneous evaluation of CNVs and SNVs/indels to enhance the diagnostic yield and timely TAT, especially for cases in the late second trimester or third trimester.

X-linked dominant protoporphyria in a Chinese pedigree reveals a four-based deletion of ALAS2.

BACKGROUND: X-linked dominant protoporphyria (XLDPP) is a rare, hereditary disorder that leads to hepatobiliary and hematologic abnormalities including increased erythrocyte protoporphyrin, cutaneous photosensitivity, and decreased iron stores that is caused by a pathogenic mutation of ALAS2 gene. METHODS: This study aimed to confirm the existence of XLDPP in a Chinese pedigree. We observed and described the dermatoscopic findings of this disorder under dermoscopy, and assessed photo damage in XLDPP patients using the Fotofinder system and very high frequency (VHF) skin ultrasonic system. We performed next generation sequencing and Sanger sequencing to detect and confirm genetic variants in DNA samples from the XLDPP family. Moreover, we monitored the hepatobiliary function as well as hematologic changes in related family members. RESULTS: As compared to unaffected control subjects, patients exhibited evidence of severe cutaneous photodamage, causing photoaging, an increase in the size of the gallbladder, increased levels of protoporphyrin in red blood cells, an increase in blood levels of uroporphyrin and hematoporphyrin, and iron deficiency. CONCLUSIONS: XLDPP was validated by the identification of a four-base-pair deletion (c.1706_1709delAGTG, p.E569fs) in ALAS2 (NM_000032.4) in the proband which segregated with the disease in an X-linked dominant pattern, with hemizygous males being more severely affected than heterozygous females. We also found a missense variant in GATA Binding Protein 1 (GATA1).

Prenatal diagnosis of lingual cyst and spontaneous regression before birth: A rare case report and literature review.

RATIONALE: We report a case of fetal lingual cyst that was diagnosed prenatally using 2-dimensional and 3-dimensional images during routine second trimester screening. To the best of our knowledge, this is the first description of a cystic lesion disappearing before birth. PATIENT CONCERNS: A 36-year-old woman at 22 weeks' gestation showed the presence of an oral cystic lesion in routine second trimester ultrasound screening. The lesion measured 18 × 15 × 15 mm. INTERVENTIONS: A follow-up ultrasound examination was performed every 4 to 6 weeks. OUTCOMES: The cyst disappeared in a follow-up ultrasound examination at 35 and 37 weeks of gestation. A male newborn who weighed 3480 g was delivered with no feeding difficulties. The boy was followed to 6 years after birth. The child had normal growth and development, and there was no recurrence of the cyst. LESSONS: Prenatally diagnosed lingual cysts are uncommon findings that can include many different pathologies with a wide spectrum of severity. Lingual cysts usually have a good prognosis.

Two case reports: Early detection of amniotic band syndrome by adhesion between hand and umbilical cord at 11 to 14 weeks' gestation.

RATIONALE: The significant ultrasonic characteristics of amniotic band syndrome (ABS) are the malformations of fetal affected parts and the band-like echoes in amniotic cavity. This article first suggests that the fetal hand adhered to umbilical cord with restricted movement provides some values in the diagnosis of ABS in early gestational weeks especially when the fetal malformation is not obvious and amniotic band is thin and fine. PATIENT CONCERNS: Two pregnant women had no discomfort and underwent routine ultrasound examination at 11 to 14 gestational weeks. DIAGNOSIS: Only the fetal hand adhered to umbilical cord with restricted movement was detected during the first ultrasound examination at 11∼14 gestational weeks, and the floating band-like echos were detected in the amniotic cavity with follow-up examinations 2 to 3 weeks later. Both of the 2 fetus were diagnosed as ABS by ultrasound INTERVENTIONS:: The two pregnant women underwent the prenatal counseling and were recommended closely follow-up and further examination. OUTCOMES: Two fetuses died in utero between 17 and 19 weeks. After induction of labor, it was found that the hands and umbilical cord of the fetuses were wrapped by amniotic bands, which was proved pathologically as ABS. LESSONS: The adhesion of the fetal hand and umbilical cord is an important ultrasonic sign suggesting ABS with poor prognosis in early pregnancy. We hope that this study can provide some guidance for the early diagnosis of ABS during 11 to 14 week's ultrasound examination.

Chinese fetal biometry: reference equations and comparison with charts from other populations.

OBJECTIVE: This study aimed to construct new reference charts and equations for fetal biometry from Chinese fetuses at 15-40 weeks and to compare them with previous references. METHOD: This was a prospective, cross-sectional study of singleton pregnancies in patients with a confirmed gestational age who underwent ultrasound examinations between the 15th and 40th weeks of gestation. Each woman was selected only once for this study. Biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) were recorded. For each measurement, separate regression models were fitted to estimate the mean and standard deviation at each menstrual age. Z-scores were calculated with our reference equations for comparison with other references. RESULTS: New charts and reference equations involving 7553 Chinese women were created for BPD, HC, AC, and FL. Reference equations were cubic models. Prediction intervals for the new reference charts were similar to those of previous references, but with some slight differences. The main difference in our fetal biometric measurements compared with those of Korea and Hong Kong was the FL. CONCLUSIONS: We report new Chinese reference charts and equations for fetal biometry. These reference charts and equations are available for clinical use in obstetric ultrasound studies for the Chinese population.

Evaluation of renal artery stenosis with hemodynamic parameters of Doppler sonography.

OBJECTIVE: The purpose of this study was to determine the values of the hemodynamic parameters of Doppler sonography in the diagnosis of renal artery stenosis (RAS) (diameter reduction >/=50%) and to investigate their possible influencing factors. METHODS: Five Doppler parameters, including renal peak systolic velocity (RPSV), renal-aortic ratio (RAR), renal-renal ratio (RRR), renal-segmental ratio (RSR), and renal-interlobar ratio (RIR), were measured in 81 patients before arteriography. Arteries with >/=50% diameter reduction were considered stenosed at renal arteriography. Receiver operating characteristic curve analysis was performed to determine the optimal parameters. The sensitivity, specificity, positive and negative predictive values, and accuracy at various threshold values were calculated. RESULTS: Sixteen accessory renal arteries (15 normal, one mild stenosis) were identified at arteriography. Of the 153 main renal arteries demonstrated at arteriography, 79 were normal or demonstrated stenosis <50%, 68 demonstrated moderate stenosis (50%-99%), and 6 demonstrated total occlusion. Doppler sonographic examination was technically successful in 91.7% (154/168) of main and accessory renal arteries. The optimal threshold values of RPSV, RAR, RRR, RSR, and RIR were 170 cm/s, 2.3, 2.0, 4.0, and 5.5, respectively. The parameters RPSV, RSR, and RIR showed good diagnostic results with accuracies equal to or greater than 88%, whereas RAR and RRR presented a sensitivity of only 76.47%. The diagnostic accuracies of RPSV, RAR, and RRR were approximately 3% higher after exclusion of the eight patients with abdominal aorta stenosis. CONCLUSION: It should be feasible and necessary to measure three representative hemodynamic parameters (RAR, RPSV, and RIR or RSR) in the diagnosis of >/=50% RAS. The PSVs in the abdominal aorta and renal artery can be affected by factors other than RAS, which may decrease the accuracy of RAR. However, post-PSV ratios are minimally affected by PSV in the abdominal aorta or by an equal proportional change in PSVs in the renal artery trunk and its intrarenal renal arteries; therefore, use of post-PSV ratios dramatically overcomes some limitations of RAR.

Trisomy 22 with long spina bifida occulta: A case report.

INTRODUCTION: Complete non-mosaic trisomy 22 is a fatal chromosomal disorder that only few fetuses can survive over 12 weeks as reported. Prenatal sonographic findings combined with postnatal or postmortem discoveries showed characteristic multi-systematic anomalies. PATIENT CONCERNS: The unborn baby of a 35-year-old pregnant woman was found to have several anomalies during a prenatal sonographic scan, including intrauterine growth retardation, ventricular septal defect, flat facial profile, and unclear bilateral kidney structures. DIAGNOSES: The fetus was diagnosed as having complete non-mosaic trisomy 22 by chromosomal analysis. INTERVENTIONS: The pregnancy was terminated at 24 weeks, and autopsy was permitted. OUTCOMES: Postmortem examinations revealed additional long-sectional spina bifida occulta and imperforate anus. CONCLUSIONS: This was the first time a case of spinal cord defect was reported in trisomy 22 fetuses. More attention should be paid to the spinal cord during sonographic examinations in trisomy 22 fetuses.

Adducted thumb as an isolated morphologic finding: an early sonographic sign of impaired neurodevelopment: A STROBE compliant study.

Fetal adducted thumbs have been described in association with hydrocephalus and other abnormalities, but in cases without other structural malformations the determination of prognosis and recurrence risk is challenging. The aim of our study is to analyze the characteristics, natural history, and postnatal outcome of such cases.A retrospective study was conducted over a period of 4 years in a tertiary referral center. All fetuses diagnosed as adducted thumbs without other structural malformations comprised the study group. Prenatal sonographic features and neonatal outcome are documented.There were 4 cases of fetal adducted thumbs diagnosed during the study period. No cases demonstrated other structural malformations throughout the gestation. A smaller head was noted in 2 cases during the follow-up, and all cases presented with polyhydramnios on the first or ensuing scans. Three cases died after birth due to swallowing or breathing difficulty, and the surviving 1 showed convulsion and mental retardation.Fetal adducted thumb might be an early and specific sonographic marker of impaired neurodevelopment. Close follow-up and genetic investigation should be performed in these cases. Ultrasound examination plays an important role in the prenatal diagnosis and counseling of cases without detailed prenatal genetic analysis.

Ultrasonographic features of medullary thyroid carcinoma and their diagnostic values.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare malignant tumour and usually difficult to diagnose with ultrasound. The aim of the study is to summarize the sonographic features of MTC and evaluate their diagnostic values. METHODS: We analyzed the sonographic features of 35 MTCs and 50 benign nodules with respect to nodular size, echogenecity, internal content, shape, height/width, border, peripheral halo, calcifications and colour flow pattern. The ratio of long to short axis, echogenecity, internal content and calcifications were also assessed in cervical lymph nodes. The differences in sonographic features between MTCs and benign nodules were analyzed with Chi square test. The diagnostic efficiency of each sonographic feature was determined. RESULTS: The main sonographic features of MTC were hypoechogenicity (including marked hypoechogenicity) (n = 34, 97%), internal solid content (n = 29, 83%), taller than wide (n = 34, 97%), well defined border (n = 24, 69%), microcalcifications or macrocalcifications (n = 23, 66%). The echogenicity, internal content, shape, peripheral halo and calcifications were significantly different between these two groups, while the tall/wide, border, and perinodular and intranodular vascularisation were not significantly different. Among all the individual sonographic features, irregular shape had the highest diagnostic efficiency with a sensitivity of 51% and specificity of 92%. The combination of marked hypoechogenicity, microcalcifications, and irregular shape yielded a sensitivity of 77% and specificity of 86%. CONCLUSIONS: The typical sonographic features of MTC are hypoechogenicity, predominantly solid, irregularly shaped with intranodular micro- or macro-calcifications. The combination of multiple sonographic features is helpful, but not definitive, for the diagnosis of MTC.

Evaluation of acute renal artery thrombosis or embolism with color Doppler sonography.

OBJECTIVE: This study aimed to evaluate the value of color Doppler sonography (CDS) in the diagnosis of acute renal artery thrombosis or embolism (ARATE). METHODS: We retrospectively reviewed the CDS findings of 10 patients with ARATE, which were confirmed by the clinical data and digital subtraction angiography or computed tomography (n=8) or by the results of surgical pathology (n=2). We analyzed the echogenicity and size of the kidneys on gray-scale images and blood flow parameters of the main renal artery, renal vein, and the intrarenal artery (segmental or interlobar artery) of the kidneys on CDS in all cases. RESULTS: Four patients with acute main renal artery thrombosis (two transplanted kidneys and two native kidneys) correctly detected by CDS underwent emergency thrombolysis via renal artery. The results of CDS in six native kidneys with renal artery embolism included two cases with satisfactory CDS demonstrations, two cases with undetermined CDS findings, one case interpreted as severe renal artery stenosis, and one misdiagnosed case. CONCLUSIONS: CDS is a useful imaging tool in the diagnosis of large renal infarcts caused by thrombosis or embolism in the main renal artery. However, small infarcts, which need other imaging modalities for further evaluation and confirmation, may be neglected by CDS.

Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages.

Adult bone-marrow-derived mesenchymal stem cells (MSCs) are well-established as having the capacity to differentiate into cells with mesodermal, ectodermal, and endodermal characteristics and can leave their niche to home toward and engraft within foreign tissues. To investigate whether adult MSCs contribute to the repair of skin appendages after injury, BrdU-labeled MSCs were co-cultured with heat-shocked confluent sweat gland cells (SGCs) in vitro and later intravenously injected into full-thickness skin wounds in rats. When adult MSCs were co-cultured with heat-shocked SGCs, a subset of adult MSCs differentiated into SGCs, the percentage of differentiation being enhanced by epidermal growth factor and the injured microenviroment, but weakened by PD98059. The ERK (extracellular signal-regulated kinase) pathway, especially pERK, was involved in the phenotype conversion of human MSCs into human SGC. Labeled MSCs were noted in hair follicles, sebaceous glands, blood vessels, and dermis in full-thickness wounds, and the incorporated cells in hair follicles and sebaceous glands were also positive for pan-cytokeratin. After wound healing, some labeled MSCs returned to the bone marrow, whereas other were retained in the dermis. We conclude that adult MSCs have the capacity to dock at specific sites, to contribute to wound healing of skin appendages, and to home toward marrow, and that engraftment of bone-marrow-derived cells is a functional event.

[The involvement of ERK pathway in the cellular phenotype conversion in human mesenchymal stem cells cocultured with human sweat gland cells].

OBJECTIVE: To study the cellular phenotype conversion of human mesenchymal stem cells (MSCs) cocultured with human sweat gland cells (SGCs) and the contribution of extracellular signal-regulated kinase (ERK) pathway in the process. METHODS: MSC and SGC were isolated, amplified , and identified with two-step immunohistochemistry method. The primary SGCs were heat-shocked at 47 degrees C. Then the supernatants were collected immediately and 24hr later. The 3rd passage of MSCs were divided into control, SGC supernatant (cells were cultured in DMEM/F12 medium containing 30% SGC supernatant), SGC supernatant + EGF (cells were cultured in DMEM/F12 medium containing 30% SGC supernatant and 50 microg/L EGF), and SGC supernatant + PD98059 (cells were cultured in DMEM/F12 medium containing 30% SGC supernatant and 10 micromol/L PD98059) groups. The positive expression of CK7and CEA in MSCs were detected on the 7th post-stimulation day (PSD) by flow cytometry. The expression of ERK and phosphorylated ERK were determined with Western blotting. RESULTS: The positive expression rate of CK7 and CEA was (5.76 +/-0.10)%, (2.01 +/- 0.09)% in SGC supernatant group; (7.31 +/- 0.21)% and (7.27 +/- 0.12)% in SGC supernatant + EGF group; and (1.63 +/- 0.11)%, (1.54 +/- 0.07)% in SGC supernatant + PD98059 group; they were all obviously higher than that in control group (P < 0.01). Moreover, ERK expression was observed in all groups. The expression of pERK in SGC supernatant + EGF group was higher than that in SGC supernatant group, but almost no expression of pERK was found in the SGC supernatant + PD98059 and control groups. CONCLUSION: Indirect coculture of MSCs with SGCs can induce the phenotype conversion of MSCs through ERK pathway.