Endometriosis of the lung: A case report and review of literature.

BACKGROUND: Lung endometriosis is an extremely rare gynecological disease. Current literature reports suggest that the majority of patients will present with only generic symptoms, such as hemoptysis, pneumothorax, and hemopneumothorax, which often leads to misdiagnosis. To date, there are 18 case reports of lung endometriosis that describe the clinical manifestation, imaging changes, treatment, and prognosis of the disease. To provide further insights into this rare disease, we present a new case report and a brief review of pulmonary endometriosis. CASE SUMMARY: We report here about a 19-year-old woman who was admitted to the hospital for repeated catamenial hemoptysis over a 3-mo period. computed tomography (CT) imaging during menstruation revealed patchy high-density shadows, approximately 0.5 cm3 in size, in the right middle lobe of the lung. The patient's hemoptysis and changes in the CT scans resolved after menstruation. Thoracoscopic right middle lobectomy, right lower lung repair, and closed thoracic drainage were performed. Postoperative histopathology confirmed lung endometriosis. There was no recurrence of symptoms at the 6 mo follow-up. CONCLUSION: We propose diagnosing lung endometriosis by thoroughly taking reproductive history, clinical details, imaging, and histopathology followed by treatment with surgical resection.

A case of death of patient with ovarian fibroma combined with Meigs Syndrome and literature review.

Ovarian fibroma is the most common benign pure stromal tumor. It has no specific clinical manifestation, most of which are pelvic or adnexal masses. 10-15% of cases with hydrothorax or ascites, after tumor resection, hydrothorax and ascites disappear, known as Meigs Syndrome. The elevated level of CA125 in a few patients was easily misdiagnosed as ovarian malignant tumor. A case of bilateral Ovarian fibroma associated with Meigs Syndrome is reported and the literature is reviewed in order to improve the understanding of the changes and avoid misdiagnosis.

Integrated effects of microbial decomposing inoculant on greenhouse gas emissions, grain yield and economic profit from paddy fields under different water regimes.

Few studies have comprehensively evaluated the impacts of microbial decomposing inoculants on greenhouse gas emissions and economic profit from paddy fields under different water regimes. Here, this study evaluated the effects of microbial decomposing inoculant treatments (straw returning without or with microbial decomposing inoculants (S and SMD)) on rice yield, CH4 and N2O emissions, economic profit and net ecosystem economic profit (NEEP) from paddy fields under different water regimes (continuous flooding (CF) and alternate wetting and drying irrigation (AWD)) in central China with a two-year field experiment. Compared with S treatment, SMD treatment significantly increased the rice yield and crop water productivity by 6.6-7.2% and 5.6-7.9%, respectively. AWD treatment significantly enhanced the crop water productivity by 56.9-73.7% while did not affect rice yield relative to CF treatment. Regardless of water regimes, SMD treatment did not affect N2O emissions, but significantly increased CH4 emissions by 13.8-39.6% relative to S treatment, resulting in a remarkable enhancement of global warming potential by 13.5-32.5%. Compared with S treatment, SMD treatment improved the economic profit and NEEP. By contrast, AWD treatment significantly increased N2O emissions by 19.1-64.8% compared with CF treatment, but significantly reduced CH4 emissions by 35.3-79.1%. Accordingly, AWD treatment significantly decreased the global warming potential by 33.4-73.9% compared with CF treatment. In addition, AWD treatment resulted in 39.9-96.4% higher economic profit and 48.0-124.4% higher NEEP relative to CF treatment. In summary, AWD treatment is a sustainable water regime that can maintain rice yield, mitigate global warming potential, and increase economic income. However, regardless of water regimes, SMD treatment led to higher rice yield and economic profit, as well as higher global warming potential than S treatment, suggesting that other appropriate treatments of crop straw are needed to mitigate CH4 emissions while improving economic profit for rice sustainable production.

TGF-ß2-induced NEAT1 regulates lens epithelial cell proliferation, migration and EMT by the miR-26a-5p/FANCE axis.

AIM: To explore the regulatory mechanism of nuclear paraspeckle assembly transcript 1 (NEAT1) in the pathogenesis of posterior capsule opacification (PCO). METHODS: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was executed to analyze NEAT1 and microRNA (miR)-26a-5p expression in transforming growth factor-beta 2 (TGF-ß2)-disposed lens epithelial cells (LECs). The proliferation, cell cycle progression, apoptosis, and migration of TGF-ß2-disposed LECs were evaluated. The relationship between NEAT1 or fanconi anemia (FA) complementation group E (FANCE) and miR-26a-5p was verified by dual-luciferase reporter assay. RESULTS: TGF-ß2 induced NEAT1 expression in LECs. NEAT1 inhibition accelerated apoptosis, cell cycle arrest, decreased proliferation, epithelial-mesenchymal transition (EMT), and migration of TGF-ß2-disposed LECs. NEAT1 sponged miR-26a-5p to further regulate FANCE expression. Rescue experiments presented that miR-26a-5p downregulation overturned NEAT1 silencing-mediated impacts on TGF-ß2-disposed LEC biological behaviors. Additionally, FANCE overexpression reversed miR-26a-5p mimic-mediated impacts on TGF-ß2-disposed LEC biological behaviors. CONCLUSION: TGF-ß2-induced NEAT1 facilitates LEC proliferation, migration, and EMT by upregulating FANCE via sequestering miR-26a-5p.

Effects of straw returning levels on carbon footprint and net ecosystem economic benefits from rice-wheat rotation in central China.

Straw returning usually gives rise to greenhouse gas (GHG) emissions from the soil, and thus negatively affects carbon footprint (CF) of crop production. Numerous studies reported the effects of straw returning on the CF from single crop production. However, little is known about the integrated effects of different levels of straw returning on the CF and net ecosystem economic benefits (NEEB) from rice-wheat rotation. Here, we investigated the effects of different amounts of straw returning on soil CH4 and N2O emissions, GHG emissions from agricultural inputs (AIGHG), CF, and NEEB from a 2-year cycle of rice-wheat rotation. The CF was determined based on the total GHG emissions associated with crop production inputs and services. Overall, straw returning significantly increased annual CH4 emissions by 5.4-72.2% and reduced annual N2O emissions by 3.3-31.4% compared with straw removal. Straw returning remarkably increased rice grain yields by 8.1-9.9% and wheat grain yields by 10.2-21.1% compared with straw removal. The average annual AIGHG from rice-wheat rotation ranged from 3579 to 4987 kg CO2-eq ha-1. Diesel consumption played a dominant role in the AIGHG. The annual CF ranged from 0.96 to 1.31 kg CO2-eq kg-1 and increased with increasing straw returning amounts. The NEEB, which ranged from 14161 to 17413 CNY ha-1, was significantly affected by the levels of straw returning. The treatment with returning of 1/3 of preceding crop straw to the field (2.19-2.47 kg ha-1 year-1 of rice straw in the wheat season and 1.38-1.68 kg ha-1 year-1 of wheat straw in the rice season) resulted in relatively higher grain yield, the lowest CF, and the highest NEEB among all treatments, and thus can reduce CF, and increase grain yields and NEEB, and thus can be recommended as a sustainable approach to mitigate GHG emissions and increase economic benefits from rice-wheat rotation.

Medullary thyroid carcinoma combined with papillary thyroid carcinoma: case report and literature review.

We investigated the clinicopathologic features, immunophenotype, (differential) diagnosis, pathogenesis, treatment, and follow-up of medullary thyroid carcinoma (MTC) combined with papillary thyroid carcinoma (PTC). A retrospective analysis of the clinical and pathologic features and immunophenotype was conducted in a patient with MTC and PTC. Relevant literature was also reviewed. Results of thyroid fine needle aspiration indicated malignant tumor in the right lobe of the thyroid, suggesting PTC; further analysis by biopsy confirmed this diagnosis. The left lobe exhibited MTC. Tumor metastases were absent from the lymph nodes of the left central area (0/2), and no tumor was present in the thymic tissue. In the right lobe and isthmus, PTC was observed, with a maximum infiltration diameter of 0.8 cm, and tumor metastases were absent from lymph nodes of the right central area (0/3). Immunohistochemistry of the left lobe was positive for calcitonin, CK, TTF-1, CD56, CgA, and Congo red, but negative for CK19, thyroglobulin, galectin-3, MC, and CEA, with a Ki-67 proliferation index of 1%. The right lobe was positive for CK19, galectin-3, and MC, but negative for CD56. The V600E mutation was detected in BRAF. MTC combined with PTC is a rare thyroid tumor. This condition is diagnosed mainly based on morphology, immunophenotyping, and molecular detection. It must be distinguished from other malignancies, such as thyroid follicular tumors, undifferentiated carcinoma, poorly differentiated carcinoma, transparent stellate tumor, and mixed PTC/MTC. Surgery and post-operative drug administration currently constitute the preferred treatments.

ALK-1-positive inflammatory myofibroblastic tumor of the thyroid complicated by Hashimoto's thyroiditis: report of a rare case and a literature review.

BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) of the thyroid are extremely rare soft-tissue tumors. In the literature, IMTs are sometimes called plasma cell granulomas (PCGs) or inflammatory pseudotumors, which often causes ambiguity. To date, 17 cases of PCGs and five cases of thyroid IMTs have been reported. These cases reveal that IMTs of the thyroid are often negative for the anaplastic lymphoma kinase (ALK-1) gene. To provide further information on this rare lesion, we present a case of an ALK-1-positive thyroid IMT and a review of IMTs of the thyroid. CASE PRESENTATION: A 34-year-old Chinese woman presented with a painless neck mass that had persisted for over a month. Ultrasonography revealed a 4.28 × 2.53 cm2 hypoechoic mass, in the left lobe of the thyroid gland. Serum levels of thyroglobulin and anti-thyroglobulin antibodies were high. Subsequently, left lobectomy was performed. Macroscopically, the lesion was a gray-brown nodular mass with a partial envelope. Histologically, two different lesion types were observed. The first lesion showed classic spindle cell proliferation, with spindle cells arranged in fascicles, accompanied by mature inflammatory cells. The other lesion showed a large number of infiltrating lymphocytes, with lymphoid follicles in the remaining thyroid gland, which was atrophic. Immunohistochemical staining showed that the spindle cells were negative for CK19, CyclinD1, Gelectin-3, EMA, CD34, S100, Bcl-2, and STAT-6, but strongly positive for ALK-1, vimentin, and TTF1. CK was focally expressed, and the Ki-67 index was 5%. A diagnosis of IMT was proposed according to immunohistochemical findings and morphology. Hashimoto's thyroiditis was confirmed according to serum levels of thyroglobulin and anti-thyroglobulin antibodies and morphology. The patient did not receive adjuvant therapy. She remained alive without disease recurrence for 10 months after lobectomy. CONCLUSIONS: IMTs should be considered in the diagnosis when spindle cell proliferation accompanied by mature inflammatory cells is observed, spindle cells are mildly atypical, and myofibroblast differentiation is present in the thyroid. A uniform diagnostic term is crucial to avoid ambiguity. Clinicians and pathologists should be aware of the necessity for long-term follow-up, especially in ALK-positive cases. The therapeutic potential of ALK-1 positivity should be explored further.

c-Jun N-terminal kinase 3 deficiency protects axotomized retinal ganglion cells via affecting mitochondria involved apoptosis pathway.

AIM: To illustrate the isoform-specific role and mechanism of c-Jun N-terminal kinases (JNKs) in mouse optic nerve axotomy induced neurotrauma. METHODS: We firstly investigated the expression of JNK1, JNK2, and JNK3 in the retinal ganglion cells (RGCs) by double-immunofluorescent staining. Then we created optic nerve axotomy model in wild type as well as JNK1, JNK2, JNK3, isoform specific gene deficiency mice. With that, we checked the protein expression profile of JNKs and its active form, and quantified the survival RGCs number by immunofluorescence staining. We further explored the molecules underlying isoform specific protective effect by real-time polymerase chain reaction (PCR) and Western blotting assay. RESULTS: We found that all the three isoforms of JNKs were expressed in the RGCs. Deficiency of JNK3, but not JNK1 or JNK2, significantly alleviated optic nerve axotomy induced RGCs apoptosis. We further established that expression of Noxa, a pro-apoptotic member of BH3 family, was significantly suppressed only in JNK3 gene deficiency mice. But tumor necrosis factor receptor 1 (TNFR1) and Fas, two key modulators of death receptor mediated apoptosis pathway, did not display obvious change in the expression. CONCLUSION: It is suggested that mitochondria mediated apoptosis, but not death receptor mediated apoptosis got involved in the JNK3 gene deficiency induced RGCs protection. Our study provides a novel insight into the isoform-specific role of JNKs in neurotrauma and indicates some cues for its therapeutics.

Giant recurrent mixed-type liposarcoma of the retroperitoneum: report of a case and review of literature.

Retroperitoneal liposarcoma is a rare tumor with an incidence of 2.5 per million individuals, especially tumors of mixed histologic pattern. We present a case of a 63-year-old woman with a history of slowly increasing abdominal volume over 2 years. The diagnosis of giant and multiple retroperitoneal mass suspected of liposarcoma was confirmed by computed tomography. The patient underwent resection of 7 tumor masses together weighing 5 kg. The microscopic diagnosis was mixed-type liposarcoma of the retroperitoneum. 8 months after surgery, the patient suffered multiple metastases in the liver and abdominal wall, and upper digestive tract hemorrhage. Although this type of tumor is rarely seen, tumor tissue should be thoroughly gathered and analyzed on histologic examination to reach final diagnosis. Knowledge of the subtype of liposarcoma is important for proper prognosis and treatment of the patient. To the best of our knowledge, this is the first report of mixed-type retroperitoneal liposarcoma with three components described in the English literature.

MicroRNA-384-3p inhibits retinal neovascularization through targeting hexokinase 2 in mice with diabetic retinopathy.

Diabetic retinopathy (DR) presents a microvascular complication of diabetes, which may contribute to visual impairment. The treatment of DR is still controversial. Accumulating studies have reported the role of microRNAs (miRs) in DR. This study aims to explore the functions of microRNA-384-3p (miR-384-3p) in retinal neovascularization by targeting hexokinase 2 (HK2) in mice with DR. A total of 43 C57BL/6 male mice were selected and divided into normal ( n = 16) and DR ( n = 27) groups. Retinal microvascular endothelial cells (RMECs) were collected from the normal and DR mice and mainly treated with a miR-384-3p mimic, a miR-384-3p inhibitor, small interfering RNA (siRNA) against HK2 and HK2 overexpression plasmids to understand the underlying regulatory mechanisms of miR-384-3p. The relationship between miR-384-3p and HK2 was determined by dual-luciferase reporter assay. The miR-384-3p expression and the mRNA and the protein expressions of HK2 and CD31 in retinal tissues and cells were evaluated using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tube formation was observed by conducting a tube formation experiment. HK2 is a target gene of miR-384-3p. The DR mice showed higher expression of HK2 and CD31 but lower expression of miR-384-3p. The miR-384-3p mimic and siRNA-HK2 reduced the expression of HK2, decreased cell proliferation and tube formation of RMECs, whereas the miR-384-3p inhibitor could reverse these trends. Our study demonstrates that overexpression of miR-384-3p inhibits retinal neovascularization in DR mice via inhibition of HK2.

Integrated rice-duck farming decreases global warming potential and increases net ecosystem economic budget in central China.

Over the past decades, many attempts have been made to assess the effects of integrated rice-duck farming on greenhouse gas emissions, use efficient of energy, soil fertility, and economic significance. However, very few studies have been focused on the effects of the farming on net ecosystem economic budget (NEEB). Here, a 2-year field experiment was conducted to comprehensively investigate the effects of ducks raised in paddy fields on CH4 and N2O emissions, global warming potential (GWP), rice grain yield, and NEEB in central China. The experiment included two treatments: integrated rice-duck farming (RD) and conventional rice farming (R). The introduction of ducks into the paddy fields markedly increased the rice grain yield due to enhanced tiller number and root bleeding rate. RD treatment significantly elevated the N2O emissions (p < 0.05) but decreased CH4 emissions (p < 0.05) during rice growing seasons compared with R treatment. Analysis of GWP based on CH4 and N2O emissions showed that compared with R treatment, RD treatment significantly decreased the GWP by 28.1 and 28.0% and reduced the greenhouse gas intensity by 30.6 and 29.8% in 2009 and 2010, respectively. In addition, RD treatment increased NEEB by 40.8 and 39.7% respectively in 2009 and 2010 relative to R treatment. Taken together, our results suggest that the integrated rice-duck farming system is an effective strategy to optimize the economic and environmental benefits of paddy fields in central China.

Effects of Conservation Tillage on Topsoil Microbial Metabolic Characteristics and Organic Carbon within Aggregates under a Rice (Oryza sativa L.)-Wheat (Triticum aestivum L.) Cropping System in Central China.

Investigating microbial metabolic characteristics and soil organic carbon (SOC) within aggregates and their relationships under conservation tillage may be useful in revealing the mechanism of SOC sequestration in conservation tillage systems. However, limited studies have been conducted to investigate the relationship between SOC and microbial metabolic characteristics within aggregate fractions under conservation tillage. We hypothesized that close relationships can exist between SOC and microbial metabolic characteristics within aggregates under conservation tillage. In this study, a field experiment was conducted from June 2011 to June 2013 following a split-plot design of a randomized complete block with tillage practices [conventional intensive tillage (CT) and no tillage (NT)] as main plots and straw returning methods [preceding crop residue returning (S, 2100-2500 kg C ha-1) and removal (NS, 0 kg C ha(-1))] as subplots with three replications. The objective of this study was to reveal the effects of tillage practices and residue-returning methods on topsoil microbial metabolic characteristics and organic carbon (SOC) fractions within aggregates and their relationships under a rice-wheat cropping system in central China. Microbial metabolic characteristics investigated using the Biolog system was examined within two aggregate fractions (>0.25 and <0.25 mm). NT treatments significantly increased SOC concentration of bulk soil, >0.25 aggregate, and <0.25 mm aggregate in the 0-5 cm soil layer by 5.8%, 6.8% and 7.9% relative to CT treatments, respectively. S treatments had higher SOC concentration of bulk soil (12.9%), >0.25 mm aggregate (11.3%), and <0.25 mm aggregate (14.1%) than NS treatments. Compared with CT treatments, NT treatments increased MBC by 11.2%, 11.5%, and 20%, and dissolved organic carbon (DOC) concentration by 15.5%, 29.5%, and 14.1% of bulk soil, >0.25 mm aggregate, and <0.25 mm aggregate in the 0-5 cm soil layer, respectively. Compared with NS treatments, S treatments significantly increased MBC by 29.8%, 30.2%, and 24.1%, and DOC concentration by 23.2%, 25.0%, and 37.5% of bulk soil, >0.25 mm aggregate, and <0.25 mm aggregate in the 0-5 cm soil layer, respectively. Conservation tillage (NT and S) increased microbial metabolic activities and Shannon index in >0.25 and <0.25 mm aggregates in the 0-5 cm soil layer. Redundancy analysis showed that the SOC and its fractions (DOC and MBC) were closely correlated with microbial metabolic activities. Structural equation modelling showed that the increase in microbial metabolic activities directly improved SOC by promoting DOC in >0.25 mm aggregate in the upper (0-5 cm) soil layer under conservation tillage systems, as well as directly and indirectly by promoting DOC and MBC in <0.25 mm aggregate. Our results suggested that conservation tillage increased SOC in aggregates in the topsoil by improving microbial metabolic activities.

Type-specific detection of human papillomaviruses in Kazakh esophageal squamous cell carcinoma by genotyping both E6 and L1 genes with MALDI-TOF mass spectrometry.

BACKGROUND: Many studies have suggested a relationship between human papillomavirus (HPV) infection and the risk of esophageal squamous cell carcinoma (ESCC). However, findings are inconclusive, potentially because of geographic heterogeneity and variations in detection methods. OBJECTIVES: We sought to further investigate the prevalence of HPV with a new detection method, the MassARRAY Sequenom technique, in esophageal squamous cell carcinomas occurring in patients belonging to Kazakh populations in Xinjiang, China. STUDY DESIGN: In the present study, a novel genotyping method for detecting 30 HPV genotypes, specifically by genotyping both the HPV E6 and L1 genes with multiplex PCR using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (PCR-MS) was first adopted to evaluate HPV genotypes in 89 esophageal cancer samples and 49 matched adjacent normal esophageal tissues. RESULTS: Six HPV genotypes (HPV6, HPV16, HPV33, HPV39, HPV51, and HPV82) were present in at least 51.7% of the esophageal carcinoma tissues, which was significantly greater than 28.6% prevalence among controls (P < 0.05). HPV16 was the most common of all the genotypes investigated (HPV16 prevalence in carcinoma tissue: 49.4%; odds ratio 3.02, 95% confidence interval 1.39-6.53). HPV-positive ESCC patients were generally younger than HPV-negative patients (P = 0.04). In addition, HPV infection was more common in cases of well-differentiated and shallower invasive depth. CONCLUSIONS: Based on this new detection method, our findings reiterate the possibility that HPV infection (especially HPV16) may be involved in the etiology of esophageal carcinoma in the Kazakh populations and that HPV E6 gene positivity may be associated with prognosis of patients.

The effects of rape residue mulching on net global warming potential and greenhouse gas intensity from no-tillage paddy fields.

A field experiment was conducted to provide a complete greenhouse gas (GHG) accounting for global warming potential (GWP), net GWP, and greenhouse gas intensity (GHGI) from no-tillage (NT) paddy fields with different amounts of oilseed rape residue mulch (0, 3000, 4000, and 6000 kg dry matter (DM) ha(-1)) during a rice-growing season after 3 years of oilseed rape-rice cultivation. Residue mulching treatments showed significantly more organic carbon (C) density for the 0-20 cm soil layer at harvesting than no residue treatment. During a rice-growing season, residue mulching treatments sequestered significantly more organic C from 687 kg C ha(-1) season(-1) to 1654 kg C ha(-1) season(-1) than no residue treatment. Residue mulching significantly increased emissions of CO2 and N2O but decreased CH4 emissions. Residue mulching treatments significantly increased GWP by 9-30% but significantly decreased net GWP by 33-71% and GHGI by 35-72% relative to no residue treatment. These results suggest that agricultural economic viability and GHG mitigation can be achieved simultaneously by residue mulching on NT paddy fields in central China.

Recurrent inflammatory myofibroblastic tumors harboring PIK3CA and KIT mutations.

Inflammatory myofibroblastic tumour (IMT) is a relatively rare soft tissue malignancy. It exhibits locally aggressive behavior with a tendency for local recurrence and rare metastasis, and rare recurrent IMTs may show histological progression. The genetic hallmark of IMT is ALK rearrangement from chromosome arm 2p, but gene mutations involved in IMT remain poorly understood. The aim of the present study was to perform a pairwise comparison of the gene mutations occurring in primary and recurrent IMT from the same patient. We conducted a high-throughput analysis of 238 known mutations of 19 oncogenes in pairwise comparison primary and recurrent samples from 2 patients of IMT using Sequenom MassARRAY technology. Our results revealed 2 mutations in 2 recurrent lesion samples, including one in exon 11 of the KIT gene, resulting in a T-C substitution at position 1727 (L576P), the recurrent sample underwent histologic progression with "pleomorphic undifferentiated sarcoma-like" transformation; the other mutation was in exon 19 of the phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene, resulting in a G-A substitution at position 1624 (E542K). Moreover, no any mutation was found in the primary lesion samples from 2 patients. Our findings suggest that variable genome changes might be present in IMT, especially during the progression from a primary tumour to recurrence. To the best of our knowledge, no such longitudinal study of IMT has been undertaken previously.

Compound HRAS/PIK3CA mutations in Chinese patients with alveolar rhabdomyosarcomas.

The rhabdomyosarcoma (RMS) is the most common type of soft tissue tumor in children and adolescents; yet only a few screens for oncogenic mutations have been conducted for RMS. To identify novel mutations and potential therapeutic targets, we conducted a high-throughput Sequenom mass spectrometry-based analysis of 238 known mutations in 19 oncogenes in 17 primary formalin-fixed paraffin-embedded RMS tissue samples and two RMS cell lines. Mutations were detected in 31.6% (6 of 19) of the RMS specimens. Specifically, mutations in the NRAS gene were found in 27.3% (3 of 11) of embryonal RMS cases, while mutations in NRAS, HRAS, and PIK3CA genes were identified in 37.5% (3 of 8) of alveolar RMS (ARMS) cases; moreover, PIK3CA mutations were found in 25% (2 of 8) of ARMS specimens. The results demonstrate that tumor profiling in archival tissue samples is a useful tool for identifying diagnostic markers and potential therapeutic targets and suggests that these HRAS/ PIK3CA mutations play a critical role in the genesis of RMS.

High-throughput detection of common sequence variations of Fabry disease in Taiwan using DNA mass spectrometry.

BACKGROUND: In view of the therapeutic benefits resulting from early intervention for Fabry disease, our team has implemented an enzyme-based newborn screening in Taiwan since 2008. However, we found that most heterozygous females cannot be detected. To improve the screening efficiency, a more effective method for GLA gene genotyping is necessary. METHODS: As the suspected mutations are limited to only 29 different spots in Taiwanese, a panel of Sequenom iPLEX assay was designed for rapid screening of GLA variations. To determine the accuracy and sensitivity of this assay, previously diagnosed and undiagnosed DNA samples were analyzed by this genotyping assay and Sanger sequencing. In addition, DNA extracted from dried blood spots was also tested. RESULTS: Sequenom iPLEX assay is accurate and cost-effective, identifying the sequence variations, which were designated in the panel. It identified common GLA variants in DNA samples extracted from whole blood or dried blood spots with 100% accuracy and sensitivity. CONCLUSIONS: Sequenom iPLEX assay is suitable for Fabry newborn screening when hotspot mutations and common variations are known in a well-studied population. In addition, this assay can also be applied for first-line determination of GLA variant sequences in suspected subjects of high-risk patients, or newborns.

Clinical observations on enzyme replacement therapy in patients with Fabry disease and the switch from agalsidase beta to agalsidase alfa.

BACKGROUND: Fabry disease is an X-linked inherited lysosomal storage disease that can be treated with the enzymes of agalsidase beta (Fabrazyme) and agalsidase alfa (Replagal). Since June 2009, viral contamination of Genzyme's production facility has resulted in a worldwide shortage of agalsidase beta, leading to the switch to agalsidase alfa for patients with Fabry disease in Taiwan. METHODS: The medical records were retrospectively reviewed for nine male patients with Fabry disease from the start of agalsidase beta treatment until the switch to agalsidase alfa for at least 1 year. RESULTS: After 12-112 months of enzyme replacement therapy (ERT), decreased plasma globotriaosylsphingosine (lyso-Gb3) was found in five out of seven patients, indicating improvement in disease severity. Among the six patients with available echocardiographic data at baseline and after ERT, all six experienced reductions of left ventricular mass index. Renal function, including microalbuminuria and estimated glomerular filtration rate, showed stability after ERT. Mainz Severity Score Index scores revealed that all nine patients remained stable at 12 months after switching to agalsidase alfa. ERT improved or stabilized cardiac status and stabilized renal function, while reducing plasma lyso-Gb3. ERT was well tolerated, even among the three patients who had hypersensitivity reactions. CONCLUSION: The switch of ERT from agalsidase beta to agalsidase alfa appears to be safe after 1 year of follow-up for Taiwanese patients with Fabry disease.

Effects of enzyme replacement therapy for cardiac-type Fabry patients with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A).

OBJECTIVE: Current studies of newborn screening for Fabry disease in Taiwan have revealed a remarkably high prevalence of cardiac-type Fabry disease with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A). DESIGN: Retrospective cohort study. SETTING: Tertiary medical centre. PARTICIPANTS: 21 patients with cardiac-type Fabry disease (15 men and 6 women) as well as 15 patients with classic Fabry disease (4 men and 11 women) treated with biweekly intravenous infusions of agalsidase ß (1 mg/kg) or agalsidase α (0.2 mg/kg) for at least 6 months. OUTCOME MEASURES: These data were collected at the time before enzyme replacement therapy (ERT) began and followed up after ERT for at least 6 months, including patient demographics, medical history, parameter changes of cardiac status and renal functions, plasma globotriaosylsphingosine (lyso-Gb3) and Mainz Severity Score Index. RESULTS: After 6-39 months of ERT, plasma lyso-Gb3 was found to be reduced in 89% (17/19) and 93% (14/15) of patients with cardiac-type and classic Fabry disease, respectively, which indicated an improvement of disease severity. For patients with cardiac-type Fabry disease, echocardiography revealed the reduction or stabilisation of left ventricular mass index (LVMI), the thicknesses of intraventricular septum (IVS) and left posterior wall (LPW) in 83% (15/18), 83% (15/18) and 67% (12/18) of patients, respectively, as well as 77% (10/13), 73% (11/15) and 60% (9/15) for those with classic type. Most patients showed stable renal function after ERT. There were statistically significant improvements (p<0.05) between the data at baseline and those after ERT for values of plasma lyso-Gb3, LVMI, IVS, LPW and Mainz Severity Score Index. No severe clinical events were reported during the treatment. CONCLUSIONS: ERT is beneficial and appears to be safe for Taiwanese patients with cardiac-type Fabry disease, as well as for those with the classic type.