Prenatal diagnosis of Noonan syndrome in a set of monozygotic twins- a case report.

BACKGROUND: We report a pair of dichorionic diamniotic (DCDA) twin pregnancy affected by Noonan syndrome (NS) with a novel mutation of LZTR1 determined by genetic analysis. CASE PRESENTATION: A pregnant woman with monozygotic twins (DCDA) at 12 + 2 weeks gestation was referred to our center. This was her second pregnancy following a previous delivery of a healthy infant. Nuchal translucency of two fetuses was 11.2 mm (CRL 62.0 mm) and 6.9 mm (CRL 62.1 mm) respectively. Ultrasound examination indicated cystic hygroma and hypoplastic ear. The couple was not consanguineous, and both had normal phenotype. Familial hereditary disease was also excluded. Under ultrasound guidance, 30 mg of chorionic villi was obtained for karyotyping, quantitative fluorescent polymerase chain reaction (QF-PCR), chromosomal microarray analysis(CMA), and Trio-whole-exome sequencing(WES) examination. We used the "target region capture and sequencing" for WES, and the BWA (Burrows Wheeler Aligner) Multi-Vision software package for the data analysis. The results of all these tests were normal except WES detected a c.427 A > G mutation in the exonic region of the LZTR1 gene and a p. Asn143Asp novel heterozygous mutation associated with NS in this pair of twins. In addition, WES suggested that the mutation in the twin fetuses originated from the mother. When the mother got the genetic test report, she came to our fetal medicine department for genetic counseling and she declined the appointment with a clinical geneticist. The couple opted to terminate the pregnancy. Because the patient did not choose to terminate the pregnancy at our hospital, we were unable to take further examination. With the help of colleagues in another hospital, photos of the fetuses were taken. Compared with the prenatal ultrasound results, the appearance of the "cystic hygroma" and "hypoplastic ear" was consistent with the ultrasound. The couple were depressed after knowing this pathogenic result and although we advised the mother to take further investigation, they refused. CONCLUSION: The mutant locus might be incompletely dominant, which led to an abnormal fetal phenotype such as cystic hygroma and hypoplastic ear.

Renal protective effect of ellipticine against streptozotocin induced diabetic nephropathy in rats via suppression of oxidative stress and inflammatory mediator

Purpose: Diabetes mellitus is a serious health problem worldwide, and diabetic nephropathy is the complication. The diabetic nephropathy considerably enhances the oxidative stress, glycation, lipid parameters and inflammatory reaction. Ellipticine has potent free radical scavenging and anti-inflammatory effect. Methods: In the current study, our objectives were to thoroughly examine the renal protective effects of ellipticine in a rat model of streptozotocin (STZ)-induced diabetic nephropathy (DN) and to elucidate the underlying mechanisms involved. For the induction of diabetic nephropathy, streptozotocin (50 mg/kg) was used, and rats were separated into groups and given varying doses of ellipticine (2.5, 5 and 7.5 mg/kg). The body weight, and renal weight were estimated. The inflammatory cytokines, renal biomarkers, inflammatory antioxidant, and urine parameters were estimated. Results: Result showed that ellipticine considerably enhanced the body weight and reduced the renal tissue weight. Ellipticine treatment significantly (P < 0.001) repressed the level of blood urea nitrogen, serum creatinine, uric acid, blood glucose and altered the lipid parameters. Ellipticine significantly (P < 0.001) repressed the level of malonaldehyde and boosted the glutathione, catalase, superoxide dismutase, and glutathione peroxidase. Ellipticine treatment significantly (P < 0.001) reduced the inflammatory cytokines and inflammatory mediators. Conclusions: Ellipticine could be a renal protective drug via attenuating the inflammatory reaction, fibrosis and oxidative stress in streptozotocin induced rats.

Selective termination of the fetus in multiple pregnancies using ultrasound-guided radiofrequency ablation.

BACKGROUND: To evaluate the perinatal outcomes in women with selective termination using ultrasound-guided radiofrequency ablation (RFA). METHODS: Complicated monochorionic (MC) twin pregnancies and multiple pregnancies with an indication for selective termination by ultrasound-guided coagulation of the umbilical cord with RFA under local anesthesia between July 2013 and Jan 2020 were reviewed. We analyzed the indications, gestational age at the time of the procedure, cycles of RFA, duration of the procedure, and perinatal outcome. RESULTS: Three hundred and thirteen patients were treated during this period. Seven of whom were lost of follow-up. The remaining 306 cases, including 266 pairs of monochorionic diamniotic (MCDA) twins (86.93%), two pairs of monoamniotic twins (0.65%), 30 dichorionic triamniotic (DCTA) triplets (1%), and three monochorionic triamniotic (MCTA) triplets (0.98%), were analyzed. Indications included twin-to-twin transfusion syndrome (TTTS) (n = 91), selective fetal growth restriction (sFGR) (n = 83), severe discordant structural malformation (n = 78), multifetal pregnancy reduction (MFPR) (n = 78), twin reverse arterial perfusion sequence (TRAPS) (n = 19), and twin anemia-polycythemia sequence (TAPS) (n = 3). Upon comparison of RFA performed before and after 20 weeks, the co-twin loss rate (20.9% vs. 21.5%), the incidence of preterm premature rupture of membranes (PPROM) within 24 h (1.5% vs. 1.2%), and the median gestational age at delivery [35.93 (28-38) weeks vs. 36 (28.54-38.14) weeks] were similar (p > 0.05). CONCLUSIONS: RFA is a reasonable option when indicated in multiple pregnancies and complicated monochorionic pregnancies. In our experience, the overall survival rate was 78.76% with RFA in selective feticide, and early treatment increases the likelihood of survival for the remaining fetus because the fetal loss rate is similar before and after 20 weeks.

An induced pluripotent stem cell line (GZHMCi004-A) derived from a fetus with heterozygous G380R mutation in FGFR3 gene causing achondroplasia.

Achondroplasia (ACH; MIM #100800) is an autosomal dominant genetic disease caused by gain-of-function mutations in FGFR3 gene and results in short-limb dwarfism. Here, we generated an induced pluripotent stem cell line GZHMCi004-A derived from umbilical cord blood mononuclear cells (UCBMCs) of a fetus with heterozygous G380R mutation in FGFR3 gene. This iPSC line is a valuable in vitro model to study the pathological mechanism and the treatment of ACH.

Improved delivery of doxorubicin by altering the tumor microenvironment using ultrasound combined with microbubbles and chemotherapy.

PURPOSE: To determine whether low-intensity pulsed ultrasound (US) using microbubbles (MB) can temporarily promote regional blood flow in the tumor and increase the delivery of doxorubicin (ad). METHODS: We randomly divided 66 tumor-bearing rabbits into 6 groups (n=11/group). The 6 groups were as follows: doxorubicin and ultrasound combined with microbubble treatment group (Ad-US-MB treatment group), US-MB treatment group, US treatment group, MB treatment group, doxorubicin treatment group (Ad-treatment group), and control group. The animals were intravenously injected with doxorubicin hydrochloride; next, the tumors in the Ad-US-MB treatment group were subjected to low-intensity ultrasound with microbubbles for 10 min. Contrast-enhanced ultrasound (CEUS) imaging of tumor tissues was performed before and after the intervention. Next, we randomly selected 8 rabbits/group, which were euthanized immediately after treatment. The remaining rabbits were reared and underwent the intervention every 7 days. RESULTS: Tumor perfusion increased immediately in the Ad-US-MB treatment group (p<0.01). Unlike the Ad treatment group, the Ad-US-MB treatment group showed high levels of doxorubicin in the tumor samples (p<0.05). Immunofluorescent staining showed high levels of doxorubicin mainly around the blood vessels; in addition, doxorubicin was observed in other areas in the Ad-US-MB treatment group. Inhibition of tumor growth was observed in the Ad-US-MB treatment group. CONCLUSIONS: Low-intensity ultrasound combined with microbubbles and chemotherapy can alter the tumor microenvironment and temporarily increase the regional blood flow to the tumor.

Ultrasound Combined With Microbubbles Increase the Delivery of Doxorubicin by Reducing the Interstitial Fluid Pressure.

The aims of this study were to determine the change of interstitial fluid pressure (IFP) after therapy using pulsed low-frequency ultrasound combined with microbubbles and to determine the change of doxorubicin penetration in VX2 tumor. In this study, all 48 tumor-bearing rabbits were divided randomly into 6 groups (n = 8 per group). These 6 groups include doxorubicin therapy together with ultrasound combined with microbubble treatment group (Ad-US-MB treatment group), US-MB treatment group, US treatment group, MB treatment group, doxorubicin treatment group (Ad treatment group), and blank control group. The animals were intravenously injected with doxorubicin hydrochloride, and then the tumors of the animals were disposed by low-intensity ultrasound and mirobubbles for 10 minutes. The IFP of tumor tissues in rabbits was detected before and after intervention. Rabbits in each group were sacrificed immediately after treatment. The concentration and the distribution of doxorubicin were detected. The tumor IFP was significantly lower than that before treatment in the Ad-US-MB treatment and US-MB treatment groups (P = 0.01, P = 0.013). Ultrasound combined with microbubble increased the concentration of doxorubicin in the sample of the Ad-US-MB treatment group compared with the Ad treatment group (P < 0.05). In immunofluorescent staining section, high concentrations of doxorubicin were observed mainly around the blood vessels, and some were even discovered at a farther area in the Ad-US-MB treatment group. The pulsed low-frequency ultrasound combined with the microbubbles enhances the vascular clearance of particles into the tumor interstitium by reducing IFP.

Bone metastasis from ovarian cancer. Clinical analysis of 26 cases.

OBJECTIVE: To study the clinical characteristics of bone metastasis from ovarian cancer, and facilitate physicians to develop treatment strategies. METHODS: This retrospective study was carried out in the Provincial Hospital Affiliated to Shandong University, Shandong, China. Twenty-six cases of bone metastasis from ovarian cancer treated between January 2002 and May 2008 were reviewed, and the clinical data were collected. RESULTS: In the current study, the incidence of bone metastasis is 0.82%. Twelve cases of bone metastasis occurred in the cervical vertebra, 10 in the lumbar vertebra, 8 in the pelvis, 7 in the thoracic vertebra, 5 in the limbs, one in the ribs, and 2 in the sternum. Lung metastasis occurred concomitantly in 9 cases, liver metastasis in 5 cases, brain metastasis in 4 cases, splenic metastasis in 3 cases, adrenal metastasis in 2 cases, and lymphatic metastasis in 12 cases. Twenty-three cases (88.5%) of bone metastasis were detected in stage III-IV, and 3 (11.5%) in stage II (p=0.000). The survival time in cases treated using comprehensive therapy was longer than those using radiotherapy or chemotherapy alone (p=0.047). CONCLUSION: Bone metastasis from ovarian cancer is rare, however, the increasing pathological stage of ovarian cancer may add to the risk of bone metastasis, especially in the cases with lung or lymphatic metastasis. The pelvis and vertebral bone are the most common location of bone metastasis, and comprehensive treatment may improve the survival time of patients.