Cyanotic Nephropathy in an Adult Patient with Eisenmenger Syndrome: A Case Report and Literature Review.

INTRODUCTION: Cyanotic nephropathy, a rare disease characterized by proteinuria, decreased estimated glomerular filtration rate, thrombocytopenia, polycythemia, and hyperuricemia, may occasionally be secondary to cyanotic congenital heart disease (CHD). There are currently no detailed diagnostic criteria or treatments for cyanotic nephropathy, owing to its extremely low incidence. Eisenmenger syndrome (ES) was initially defined by Paul Wood in pathophysiologic terms as "pulmonary hypertension (PH) at the systemic level, caused by a high pulmonary vascular resistance, with a reversed or bidirectional shunt at the aorto-pulmonary, ventricular, or atrial level." It typically develops in the presence of large, unrepaired atrial or ventricular septal defects, arterial shunts, or complex forms of CHD and is the most severe hemodynamic phenotype of pulmonary arterial hypertension associated with CHD. This study aimed to outline the case of an ES patient who developed cyanotic nephropathy and successfully achieved clinical remission through primary disease treatment and symptomatic management. Overall, this case expands our understanding of cyanotic nephropathy and lays a theoretical reference for the treatment of ES. CASE PRESENTATION: A 33-year-old Chinese female attended the outpatient department with abnormal urine test results over the past two and a half years. Following a comprehensive medical history collection, she underwent the necessary tests. Cardiac color ultrasound displayed a significant widening of the pulmonary artery and PH (severe), as well as mild tricuspid regurgitation and patent ductus arteriosus. The results of the kidney biopsy, combined with clinical findings, suggested a high risk of polycythemia-related kidney disease. She was eventually diagnosed with cyanotic nephropathy and ES. Her symptoms were relieved following symptomatic treatment, such as the administration of ambrisentan, febuxostat, and home oxygen therapy. Her follow-up visit at 6 months demonstrated improvements in hyperuricemia and a significant increase in physical strength. CONCLUSION: Cyanotic nephropathy is a rare condition in adults. Kidney biopsy remains the gold standard of diagnosis for various nephropathies. Active treatment of CHD and alleviating hypoxia may be pivotal for the treatment of cyanotic nephropathy.

Release of the additive metals from 3 commonly used plastics during the degradation under the treatment of UV irradiation.

Additive metals are continuously released into the environment during the photo-degradation of plastics into microplastics, but this phenomenon has not been reported by many studies. Herein, we investigated the surface morphology changes along with the release of additive metals (Cr, Mn, Fe, Co, Cu, Zn, and Pb) during the degradation of three types of plastics, i.e., polypropylene (PP), polyethylene terephthalate (PET) and polyvinyl chloride (PVC), under UV light irradiation. FTIR results showed that 168 days of UV-irradiation led to the primary degradation of each plastic sample. The metal release could be found after 70 days UV-irradiation. The rate of metal release for the three plastics showed the following order: PP > PET ≈ PVC. In addition, the distribution and concentrations of the metals in the plastic could influence the release characteristics of each metal. Low release rate of Fe symbolized by the total metal release in the range of 4.28 ~10.27% as evident from the results of the primary degradation experiment, indicated the release of Fe occurring in the late stage of the plastic degradation or even in the microplastics-formation stage. As for the release of Co from PP, it was far lower than that of the other elements (0.35%), showing the same release characteristics as that of Fe. On the contrary, the release ratio of Pb from PP was 78.89% and was mainly concentrated in the early stage of the plastic degradation. The results help understanding the release behavior of the additive metals during the degradation of typical plastics under ultraviolet light irradiation.

Microplastics and associated PAHs in surface water from the Feilaixia Reservoir in the Beijiang River, China.

Microplastics have been a prevalent and persistent contamination problem in the global aquatic environment. In particular, microplastics that can adsorb persistent organic pollutants (POPs) and therefore transfer these POPs to organisms in the aquatic environment have received much attention. In this study, an investigation of microplastics in the surface water of the Feilaixia Reservoir (Guangdong Province, China), which is an important part of people's daily lives in Guangdong Province was carried out, mainly focusing on the characteristics and spatial distribution of microplastics, as well as microplastics and their adsorded PAHs in the surface water of the Feilaixia Reservoir were investigated. The average abundance of microplastics in the surface water of the Feilaixia Reservoir was 0.56 ±â€¯0.45 items/m3. Six kinds of polymers, including polyethylene (PE), polypropylene (PP), polystyrene (PS), expanded polystyrene (EPS), polyvinyl chloride (PVC) and polyethylene terephthalate (PET), were identified, among which PP (52.31%) and PE (27.39%) were the major compositions. Four shapes of microplastics, i.e., foams, films, fragments and fibers were found, and films (37.78%) being the main shape. The most common typical size of the plastic particles ranged from 0.6 to 2 mm (41.36%). The total concentration of the sixteen PAHs carried on the EPS, PE and PP microplastics ranged from 282.4 to 427.3 ng/g; chrysene, benzo [ghi] perylene, and phenanthrene were abundant in the samples, at concentrations of 39.5-89.6 ng/g, 34.6-56.8 ng/g and 25.6-45.6 ng/g, respectively. Based on the ratios of the PAH isomers (Flut/Py < 1 and Phe/Ant >10), it was speculated that the source of the PAHs may be derived from the imperfect combustion of fossil fuels.

Correction to: Characteristic of microplastics in the atmospheric fallout from Dongguan City, China: preliminary research and first evidence.

Unfortunately, the original version of this article contained two mistakes.

[A preliminary exploration into medical genetics teaching to international students].

Medical education to international students has become an important part of higher education in China. Medical genetics is an essential and required course for international medical students. However, the internationalization of higher education in China has challenged the traditional teaching style of medical genetics. In this article, we discussed current situation and challenges in medical genetics teaching to international students, summarized special features and problems we encountered in teaching Indian students, and proposed some practical strategies to address these challenges and to improve the teaching.

Observation of the degradation of three types of plastic pellets exposed to UV irradiation in three different environments.

Plastic debris represents one of the most prevalent and persistent pollution problems in the marine environment. In particular, microplastics that are mainly degraded from larger plastic debris have become a growing environmental concern. However, studies on the degradation of plastics in the aquatic environment that hydrobios reside in have been limited, while several studies regarding the degradation of plastics have been conducted under outdoor or accelerated weathering conditions. Thus, observation of the degradation of three types of virgin plastic pellets exposed to UV irradiation in three different environments (i.e., simulated seawater, ultrapure water, and a waterless (air) condition) was carried out. Data on the changes in physical and chemical properties were collected. The FTIR spectra showed that hydroxyl groups and carbonyl groups developed in three types of weathered plastic pellets under the air and ultrapure water environmental conditions after 3months of UV irradiation, while only carbonyl groups were found in plastic pellets in the simulated seawater environment. In contrast, the Raman spectra showed no significant changes in the weathered plastic pellets, but there were different intensities of characteristic peaks after exposure to UV irradiation. In addition, SEM images illustrated that granular oxidation, cracks and flakes were common patterns during degradation, and the plastic pellets in the three different environments experienced different levels of chemical weathering. We suggest that further studies on the degradation processes of plastic debris are needed to predict the fate of plastic debris in the environment.

Characteristic of microplastics in the atmospheric fallout from Dongguan city, China: preliminary research and first evidence.

Microplastic pollution has exhibited a global distribution, including seas, lakes, rivers, and terrestrial environment in recent years. However, little attention was paid on the atmospheric environment, though the fact that plastic debris can escape as wind-blown debris was previously reported. Thus, characteristics of microplastics in the atmospheric fallout from Dongguan city were preliminarily studied. Microplastics of three different polymers, i.e., PE, PP, and PS, were identified. Diverse shapes of microplastics including fiber, foam, fragment, and film were found, and fiber was the dominant shape of the microplastics. SEM images illustrated that adhering particles, grooves, pits, fractures, and flakes were the common patterns of degradation. The concentrations of non-fibrous microplastics and fibers ranged from 175 to 313 particles/m2/day in the atmospheric fallout. Thus, dust emission and deposition between atmosphere, land surface, and aquatic environment were associated with the transportation of microplastics.

Intermittent pneumatic compression regulates expression of nitric oxide synthases in skeletal muscles.

This study investigated the effects of intermittent pneumatic compression (IPC) on expression of nitric oxide synthase (NOS) isoforms in compressed (anterior tibialis, AT) and uncompressed (cremaster muscles, CM) skeletal muscles. Following IPC application of 0.5, 1, and 5h on both legs of rats, the endothelial NOS (eNOS) mRNA expression was significantly up-regulated to 1.2-, 1.8, and 2.7-fold from normal, respectively, in both AT and CM, and protein expression increased more than 1.5-fold of normal at each time point. Similarly, neuronal NOS expression was up-regulated, but to a lesser degree. In contrast, inducible NOS expression was significantly and time-dependently down-regulated in both muscles. After IPC cessation, eNOS levels returned to normal in both AT and CM. The results confirm our hypothesis that IPC-induced vasodilation is mediated by regulating expression of NOS isoforms, in particular eNOS, in both compressed and uncompressed skeletal muscles. The results also suggest the importance of precisely characterizing expression of each NOS isoform in tissue pathophysiology.

Resveratrol rescued the TNF-α-induced impairments of osteogenesis of bone-marrow derived mesenchymal stem cells and inhibited the TNF-α-activated NF-кB signaling pathway.

Resveratrol, trans-3,4'-trihydroxystilbene, is a natural phytoalexin. Its anti-inflammatory activity has attracted more and more attention in clinic over the years for the treatment of inflammatory diseases. However, its effect on bone repair and new bone formation in an inflammatory microenvironment is quite little understood, especially when bone-marrow derived mesenchymal stem cells (MSCs) are used in stem cell therapy for the treatment of inflammatory bone diseases. In the present study, we investigated the effect of resveratrol on osteogenic differentiation of primary mouse bone marrow derived MSCs and potential mechanism involved when cells were exposed to TNF-α treatment. We found that resveratrol reversed the apoptotic effect of TNF-α and abrogated its inhibitory effect on osteogenic differentiation of bone marrow derived MSCs. Mechanistic studies demonstrated that resveratrol rescued the TNF-α-induced impairments of osteogenesis, and inhibited TNF-α-activated NF-κB signaling. Our study may help understand the mechanism involved in the inhibitory effect of inflammatory cytokines on osteogenic differentiation, and highlights the role of resveratrol as a potential therapeutic agent for bone repair and especially in MSC-based cell therapy for the treatment of inflammation-associated bone diseases.

Promoting Effects on Proliferation and Chondrogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells by Four "Kidney-Tonifying" Traditional Chinese Herbs.

Traditional Chinese medicine can promote the proliferation of bone marrow-derived mesenchymal stem cells (BMSCs). We chose four "Kidney-tonifying" Chinese herbal medicines, Radix Astragali, Salvia, Herba Epimedii, and Saussurea Involucrata, to evaluate whether they had positive effects on the proliferation of BMSCs and TGF-ß1-induced chondrogenic differentiation of BMSCs. The four Chinese herbal medicines were intragastrically administered to Sprague-Dawley rats, respectively, to prepare drug-containing serums of corresponding Chinese herbs. BMSCs were isolated, cultured, and exposed to culture solution containing 1%, 5%, 10%, and 15% (v/v) Radix Astragali-, Salvia-, Herba Epimedii-, and Saussurea Involucrata-containing serum, respectively. TGF-ß1-induced BMSCs were addressed in the same manner. Collagen type II protein was assessed by immunofluorescence methods. To assess whether the drug-containing serums had positive effects on the proliferation of BMSCs and TGF-ß1-induced BMSCs, MTT method was assessed. The proliferation of BMSCs was significantly enhanced when exposed to culture solutions containing 1% and 5% Radix Astragali-, 1% and 5% Salvia-, 5% Herba Epimedii-, and 1%, 5%, and 10% Saussurea Involucrata-containing serum. The proliferation of TGF-ß1-induced BMSCs was significantly enhanced when exposed to 1%, 5%, and 15% Radix Astragali-, 10% and 15% Salvia-, 5%, and 15% Herba Epimedii-, and 1%, 5%, and 10% Saussurea Involucrata-containing serum.

Role of nitric oxide in vasodilation in upstream muscle during intermittent pneumatic compression.

This study investigated the dosage effects of nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on intermittent pneumatic compression (IPC)-induced vasodilation in uncompressed upstream muscle and the effects of IPC on endothelial NOS (eNOS) expression in upstream muscle. After L-NMMA infusion, mean arterial pressure increased by 5% from baseline (99.5 +/- 18.7 mmHg; P < 0.05). Heart rate and respiratory rate were not significantly affected. One-hour IPC application on legs induced a 10% dilation from baseline in 10- to 20-microm arterioles and a 10-20% dilation in 21- to 40 microm arterioles and 41- to 70-microm arteries in uncompressed cremaster muscle. IPC-induced vasodilation was dose dependently reduced, abolished, or even reversed by concurrently infused L-NMMA. Moreover, expression of eNOS mRNA in uncompressed cremaster muscle was upregulated to 2 and 2.5 times normal at the end of 1- and 5-h IPC on legs, respectively, and the expression of eNOS protein was upregulated to 1.8 times normal. These increases returned to baseline level after cessation of IPC. The results suggest that eNOS plays an important role in regulating the microcirculation in upstream muscle during IPC.

Identification of QTLs for weight and cross-sectional area on cervical enlargement of spinal cord in mice.

Two inbred strains of mice, A/J, C57BL/6J and F2 intercross progenies,were used for QTL mapping for weight and cross-sectional area on cervical enlargement of spinal cord in mice. 13 QTLs located on Chromosome 2, 4, 8, 14, 15, 17, 18, 19 and X, respectively, for these two traits were found. Six QTLs were responsible for the cord weight, four for the cross-sectional area and three for both. Among 13 QTLs, three QTLs (P < 0.01) termed SC1 (located near D15Mit158) ,SC2 (DXMit140) and SC3 (DXMit64) accounted for 24%, 19% and 15% of the total variance in weight phenotype, and -3.78, 3.41 and 2.06 mg additive effect, respectively. The P value of other QTLs is between 0.01 and 0.05. SC1 is only one QTL that responsible for both weight and cross-sectional area in three QTLs above. This study revealed the location of major QTLs related size of spinal cord in mice, and may be helpful in fine mapping and ultimate identification of candidate genes.

Cyclic AMP-dependent protein kinase enhances SC35-promoted Tau exon 10 inclusion.

Alternative splicing of tau exon 10 generates tau with three or four microtubule-binding repeats (3R-tau or 4R-tau). The ratio of 3R-tau to 4R-tau is approximately 1:1 in the adult normal human brain. Disturbances in the ratio result in neurodegenerative tauopathies. Splicing factor SC35 acts on a SC35-like element located at the 5' end of tau exon 10 and promotes tau exon 10 inclusion. Here, we report that protein kinase (PKA) was able to interact and phosphorylate SC35. Activation or overexpression of PKA catalytic subunits promoted SC35-mediated tau exon 10 inclusion. Four PKA catalytic subunits, α1, α2, ß1, and ß2, all enhanced SC35-promoted tau exon 10 inclusion. SC35 has four putative PKA phosphorylation sites, Ser121, Ser128, Ser130, and Ser171. Pseudophosphorylation (SC354E) and blockage (SC354A) of phosphorylation of SC35 at these four sites increased and decreased, respectively, SC35's ability to promote tau exon 10 inclusion. Moreover, PKA catalytic subunits no longer further enhanced tau exon 10 inclusion when these four were mutated to either alanine or glutamate. These results suggest that PKA interacts with and phosphorylates SC35 and enhances SC35-promoted tau exon 10 inclusion. In Alzheimer's brain, down-regulation of the PKA pathway could lead to dysregulation of tau exon 10, contributing to tau pathogenesis.

5-(Hydroxymethyl)-2-furaldehyde inhibits adipogenic and enhances osteogenic differentiation of rat bone mesenchymal stem cells.

Eucommiae Cortex (Eucommia ulmoides Oliver Bark) has been used for anti-osteoporosis usually as an ethnic drug for hundred years in China. In this study, a bioactive compound, 5-(hydroxymethyl)-2-furaldehyde (5-HMF), was isolated from Eucommiae Cortex. We found that after rat bone mesenchymal stem cells (bMSCs) were induced by 5-HMF at the concentration of 0.05, 0.10 and 0.20 microg/mL in the normal medium for 7 and 14 days, the mRNA expression of ALP, COL1alpha1 (7 days only), OCN and OPN increased. However, in the adipogenic induction medium (AIM), the mRNA expression of PPARgamma, FABP4, C/EBPalpha and LPL decreased with the 5-HMF treatment. Mineralized nodule formations were enhanced after bMSCs were induced by 5-HMF for 14 and 21 days in normal medium. In the AIM medium, 5-HMF not only inhibited the formation of adipose cells obviously, but also stimulated the mineralized nodule formation after induced for 21 days. These results indicated that 5-HMF was a powerful inhibitor of adipogenesis and enhancer of osteoblastogenesis. It may be one of the constituents contributing to anti-osteoporosis in Eucommiae Cortex.

Wnt signaling pathways participate in Astragalus injection-induced differentiation of bone marrow mesenchymal stem cells.

Bone marrow mesenchymal stem cells (MSCs) have the capacity for self-renewal and multi-directional differentiation, and MSCs can differentiate into neuron-like cells under certain conditions. In this study, we used the traditional Chinese medicine Astragalus as an inducer. After 7 days of induction, the expression of specific markers was detected in each induced group by immunocytochemical staining. The results of real-time quantitative PCR and Western blot confirmed the immunocytochemistry analysis. We also tested some key genes and proteins of the Wnt signaling pathway, and found that they were increased in Astragalus-treated groups. After treatment with lithium chloride (LiCl), the protein expression of phospho GSK-3ß and ß-catenin was increased in each group compared to the corresponding group without LiCl. These findings demonstrate that Astragalus injection can induce differentiation of MSCs into neuron-like cells and suggest that the process of differentiation might be mediated by activation of Wnt signaling pathways.

Optimization of ultrasonic-assisted enzymatic hydrolysis for the extraction of luteolin and apigenin from celery.

The extraction of flavonoids is of increasing interest because of their various pharmacological effects. This study is the first attempt for the ultrasonic-assisted enzymatic hydrolysis (USAEH) applied in the extraction of 2 bioactive flavonoid compounds in celery--luteolin and apigenin. The quantitative yields of luteolin and apigenin were determined by high-performance liquid chromatography (HPLC). To achieve high yields of extracted compounds, the procedure was optimized with regard to the relative parameters involved. The optimal conditions for enzymatic hydrolysis using pectinase treatment were a reaction time of 30 min and a concentration of 0.4 mg/mL at pH 3 for luteolin and pH 5.5 for apigenin. The optimal ultrasonic parameters were an exposure period of 30 min at a temperature of 25 °C using a power source of 80 W. Under these optimal conditions, the yields of luteolin and apigenin were increased to 42.5 and 25.3 mg/g, respectively, which represented a 26.1-fold and a 32.2-fold increase in the yields of these 2 compounds, respectively, compared with the control model of aqueous extraction without enzyme or ultrasonic treatment.

[Genetic modifier loci of transplanted SP2/0 tumors in mice].

BACKGROUND & OBJECTIVE: Our previous study found that BALB/c mice are highly susceptible to transplanted SP2/0 tumors, whereas C57BL/6J mice are barely susceptible. This study was to detect genetic modifier loci that would influence the size of transplanted SP2/0 tumors using these two inbred mouse strains and their F2 progenies. METHODS: A total of 5x106 SP2/0 cells were inoculated subcutaneously in the left hide legs of 208 F2 mice derived from BALB/c and C57BL/6J strains. At the 17th day since inoculation, all mice were killed, the number and weight of transplanted tumors were recorded. A whole genomic scan using 85 microsatellite markers covering all chromosomes of the mouse, and composite interval mapping analysis were conducted in 208 F2 mice. RESULTS: Eight loci, with the percent of the total variance explanation of > or = 10% and P value of < or = 0.01, were found responsible for tumor formation. They were mapped on Chr1 (D1Mit113, 55cM and D1Mit407, 52 cM), Chr4 (D4Mit226, 41cM), Chr9 (D9Mit302, 55cM), Chr10 (D10Mit264, 42cM), Chr11 (D11Mit115, 35cM), Chr14 (D14Mit125, 45cM), and Chr18 (D18Mit123, 31cM). CONCLUSIONS: Multiple genetic variants affect individual susceptibility to transplanted SP2/0 tumors in mice. Identification of the target loci may be helpful in conformation of the haplotype and understanding of the genes responsible for tumor susceptibility or resistance.