[Research on pediatric hereditary kidney disease: from now to the future].

Hereditary kidney disease is an important cause of chronic kidney disease in children. With the progress of genome sequencing, single-cell technology, and organoid cultures, the research on hereditary kidney disease has entered a new era. How to integrate big data resources, discover new disease-causing genes, and develop effective treatment methods will be the focus of future research. This article discusses the classification, research progress, challenges and prospects of pediatric hereditary kidney disease, so as to provide valuable insights into the research of hereditary kidney disease in children.

[Research progresses on acute skin failure in children].

Acute skin failure (ASF) is an inevitable damage to the skin and subcutaneous tissue caused by hemodynamic instability and/or low perfusion. At present, there are some understandings and reports about adult ASF at home and abroad, but there are few reports about children's ASF. This article reviewed the definition, pathophysiological changes, risk factors, clinical manifestations, and management of children's ASF, and put forward suggestions in order to provide ideas for clinical diagnosis and treatment of children's ASF, and promote the further study of children's ASF.

[Study of proanthocyanidin promotes osteogenic differentiation of human periodontal ligament stem cells through the transcription factor EB-induced autophagy-lysosome pathway].

Objective: To investigate the mechanism of proanthocyanidin (PA) in regulating the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs), and to explore the effects of PA on the expression and nuclear translocation of transcription factor EB (TFEB) and on the autophagy-lysosome pathway. Methods: PDLSCs were divided into control group and PA group, which were subjected to RNA sequencing analysis (RNA Seq) to detect differentially expressed genes. The osteogenic differentiation ability and autophagy level were observed by real-time fluorescence quantitative PCR (RT-qPCR) analysis, alkaline phosphatase (ALP) staining and transmission electron microscope (TEM), respectively. Scratch assay and Transwell assay were used to detect the migration ability of PDLSCs. Lysotracker and immunofluorescence staining were used to detect the biogenesis of lysosomes. The total protein expression of transcription factor EB (TFEB) as well as that in cytoplasm and nucleus were detected by Western blotting. Confocal laser scanning microscope (CLSM) was used to observe the nuclear translocation of TFEB. The PDLSCs were treated with small interfering RNA (siRNA) technology to knock down the expression levels of TFEB gene with or without PA treatment. Western blotting was used to analyze the expressions of autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3 (LC3B), as well as osteogenic-related proteins runt-related transcription factor 2 (RUNX2), ALP, and osteocalcin in PDLSCs. Results: Compared with the control group, the osteogenic-related and autophagy-related genes showed differential expression in PDLSCs after PA treatment (P<0.05). The mRNA expression levels of osteogenic-related genes RUNX2 (2.32±0.15) and collagen type Ⅰ alpha 1 (COL1α1) (1.80±0.18), as well as the autophagy related genes LC3B (1.87±0.08) and Beclin1 (1.63±0.08) were significantly increased in the PA group, compared with the control group (1.01±0.16, 1.00±0.10, 1.00±0.07, 1.00±0.06, respectively, all P<0.01). Compared with the control group, the PA group had higher ALP activity, and more autophagosomes and autophagolysosomes observed by TEM. PA promoted the migration of PDLSCs (P<0.05) and the increased number of lysosomes and the expression of lysosomal associated membrane protein 1 (LAMP1). In the PA group, the relative expression level of total TFEB protein (1.49±0.07) and the nuclear/cytoplasmic expression of TFEB protein (1.52±0.12) were significantly higher than the control group (1.00±0.11, 1.00±0.13, respectively) (t=6.43, P<0.01; t=5.07, P<0.01). The relative nuclear/cytoplasmic fluorescence intensity of TFEB in the PA group (0.79±0.09) was increased compared with the control group (0.11±0.08) (t=8.32, P<0.01). Knocking down TFEB significantly reduced the expression of TFEB (1.00±0.15 vs 0.64±0.04), LAMP1 (1.00±0.10 vs 0.69±0.09), Beclin1 (1.00±0.05 vs 0.60±0.05), and LC3B Ⅱ/Ⅰ (1.00±0.06 vs 0.73±0.07) in PDLSCs (P<0.05, P<0.05, P<0.01, P<0.01). When TFEB gene was knocked down, the expression levels of Beclin1 (1.05±0.11), LC3B Ⅱ/Ⅰ (1.02±0.09), RUNX2 (1.04±0.10), ALP (1.04±0.16), and osteocalcin (1.03±0.15) proteins were significantly decreased in the PA group compared with the pre-knockdown period (1.28±0.03, 1.44±0.11, 1.38±0.11, 1.62±0.11, 1.65±0.17, respectively) (P<0.05, P<0.01, P<0.05, P<0.01, and P<0.01, respectively). Conclusions: PA promotes the osteogenic differentiation of PDLSCs through inducing the expression and nuclear translocation of TFEB and activating the autophagy-lysosome pathway.

[Genotype-phenotype analysis of Fabry disease caused by GLA gene variation in a pedigree].

Objective: To investigate the clinical phenotype and genetic characteristics of patients with Fabry disease caused by a GLA variant, IVS4+919G>A. Methods: It was a prospective study. Fabry disease screening was conducted among high-risk population in Ninghai from October 2021 to August 2023. Those children with decreased α-galactosidase enzyme activity<2.40 µmol/(L·h) or elavated Lyso-GL-3 level>1.10 µg/L in dried blood spot (DBS) method underwent GLA genetic testing for diagnosis confirmation. Meanwhile, family screening was carried out. A proband and his family members diagnosed with Fabry disease were research subjects. The clinical and genetic characteristics of patients with Fabry disease caused by the GLA variant (IVS4+919G>A) were analyzed. Results: The female proband aged 9.8 years with pain in both lower limbs as the initial symptom was found to have a heterozygous GLA variant IVS4+919G>A among 102 patients. In family screening, there were 4 family members (proband's father, elder sister, elder male cousin and elder female cousin) with Fabry disease and a family member (proband's fifth aunt) with a GLA variant. Among these 4 diagnosed family members, the elder male cousin of the proband, a boy aged 13.2 years had a heterozygous GLA variant, IVS4+919G>A with intermittent pain in both lower limbs as the initial symptom. The proband's father had knee joint pain. The proband's elder sister had decreased vision and his elder female cousin had no obvious symptoms. The proband's fifth aunt with a GLA variant had decreased vision. Conclusions: High-risk screening in children and family screening are helpful for early diagnosis and treatment of Fabry disease. Neuropathic pain may be a early symptom in children with Fabry disease caused by the GLA variant, IVS4+919G>A.

[5 cases of occupational heat illness].

Objective: Through the analysis of five cases of occupational heat illness caused by high temperature, we expounded the pathogenesis and summarized the clinical characteristics of heat cramp and heat exhaustion of the newly revised diagnostic criteria for occupational heat illness (GBZ41-2019), in order to prevent the occurrence of occupational heat illness to put forward controllable countermeasures. Methods: According to the occupational history, clinical diagnosis and treatment and the other relevant data submitted by five patients, the diagnosis process was analyzed and summarized. Results: Five patients developed symptoms from July to August in summer, belonging to high-temperature operation. They improved by timely treatment. The symptoms, signs and laboratory tests of the five patients were different, but they were diagnosed as occupational heat illness. Conclusion: Employers should pay attention to the high temperature protection and cooling work, and strengthen the labor protection. If patients with heat cramp and heat exhaustion were timely treated, they could basically recover. Occupational disease diagnosticians should seriously study the new diagnostic criteria of occupational disease and constantly improve their diagnostic ability.

[Effect of growth hormone supplementation on liver and lung function in patients with hypopituitarism].

To analyze the clinical features of patients with anterior hypopituitarism (HP) complicated with cirrhosis, and to explore the effects of growth hormone supplementation on liver and lung function. A total of 11 patients with HP complicated with cirrhosis admitted to Peking Union Medical College Hospital from January 2016 to December 2022 were included in the study, including 8 males and 3 females, aged [M(Q1, Q3)]31 (20, 37) years. There were 6 patients with pituitary stalk interruption syndrome, 4 patients after craniopharyngioma resection, and 1 patient after germinal cell tumor chemoradiotherapy. Cirrhosis appeared at [M(Q1, Q3)]7 (1, 16) years after the diagnosis of HP. There were 7 cases complicated with hepatopulmonary syndrome (HPS). The liver and lung function of 5 patients were improved significantly after the addition of growth hormone, and the arterial partial pressure of oxygen increased from (47±11) mmHg(1 mmHg=0.133 kPa) to (84±12) mmHg. Timely supplementation of growth hormone can improve the symptoms of fatty liver, cirrhosis and HPS, and postpone or even avoid the transplantation of liver and other organs.

Asociación entre la velocidad estimada de onda de pulso y la muerte por todas las causas en pacientes con insuficiencia cardiaca / Association between estimated pulse wave velocity and all-cause death in patients with heart failure

Antecedentes La arteriosclerosis ha demostrado ser un factor de riesgo para el desarrollo de insuficiencia cardiaca y readmisión. ePWV es un indicador novedoso, no invasivo y simple de la rigidez arterial, y este estudio tiene como objetivo investigar su relación con la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Métodos Este estudio es un estudio de cohorte que incluyó a 1.272 pacientes con insuficiencia cardiaca de los datos de NHANES de 1999 a 2018. El ePWV se dividió en tres grupos y se calculó la tasa de mortalidad acumulada de pacientes con insuficiencia cardiaca utilizando curvas de supervivencia de KM. La relación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca se representó mediante un ajuste de curva suavizado. Se utilizó análisis de regresión de COX para evaluar la asociación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Resultados La edad promedio de la población del estudio fue de 67,8±12,6 años, con 862 hombres y 650 mujeres. Durante el período de seguimiento de 12 meses, hubo 790 casos de mortalidad por todas las causas. Se utilizó un análisis de regresión de Cox para validar la relación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Los pacientes con niveles más altos de ePWV tendían a tener una tasa de mortalidad por todas las causas más alta. Después del ajuste de múltiples factores, un aumento en ePWV se asoció positivamente con la tasa de mortalidad por todas las causas (HR=1,17, intervalo de confianza [IC] del 95%: 1,12-1,22). En comparación con el tercil más bajo, la HR ajustada por múltiples variables y el IC del 95% para el tercil más alto de ePWV fueron 1,81 (IC del 95%: 1,45-2,27)... (AU)

Background Arteriosclerosis has been proven to be a risk factor for the development of heart failure and readmission. ePWV is a novel non-invasive and simple indicator of arterial stiffness, and this study aims to investigate its relationship with all-cause mortality rate in patients with heart failure. Methods This study is a cohort study that included 1272 patients with heart failure from NHANES data from 1999 to 2018. The ePWV was divided into three groups, and the cumulative mortality rate of heart failure patients was calculated using KM survival curves. The relationship between ePWV and all-cause mortality rate in heart failure patients was represented by a smoothed curve fitting. COX regression analysis was used to assess the association between ePWV and all-cause mortality rate in heart failure patients. Results The average age of the study population was 67.8±12.6 years, with 862 males and 650 females. During the 12-month follow-up period, there were 790 cases of all-cause mortality. Cox regression analysis was used to validate the relationship between ePWV and all-cause mortality rate in patients with heart failure. Patients with higher levels of ePWV tended to have a higher all-cause mortality rate. After adjustment for multiple factors, an increase in ePWV was positively associated with all-cause mortality rate (HR=1.17, 95% confidence interval [CI]: 1.12-1.22). Compared to the lowest tertile, the multivariable-adjusted HR and 95%CI for the highest tertile of ePWV were 1.81 (95%CI: 1.45-2.27). Additionally, a smoothed curve fitting was used to observe the relationship between ePWV and mortality rate, where the curve demonstrated a positive correlation between ePWV and all-cause mortality rate. Furthermore, KM survival curves indicated that all-cause mortality rate increased with the increase in ePWV. Subgroup analysis suggested a correlation between ePWV and mortality rate... (AU)

Asociación entre la velocidad estimada de onda de pulso y la muerte por todas las causas en pacientes con insuficiencia cardiaca / Association between estimated pulse wave velocity and all-cause death in patients with heart failure

Antecedentes La arteriosclerosis ha demostrado ser un factor de riesgo para el desarrollo de insuficiencia cardiaca y readmisión. ePWV es un indicador novedoso, no invasivo y simple de la rigidez arterial, y este estudio tiene como objetivo investigar su relación con la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Métodos Este estudio es un estudio de cohorte que incluyó a 1.272 pacientes con insuficiencia cardiaca de los datos de NHANES de 1999 a 2018. El ePWV se dividió en tres grupos y se calculó la tasa de mortalidad acumulada de pacientes con insuficiencia cardiaca utilizando curvas de supervivencia de KM. La relación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca se representó mediante un ajuste de curva suavizado. Se utilizó análisis de regresión de COX para evaluar la asociación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Resultados La edad promedio de la población del estudio fue de 67,8±12,6 años, con 862 hombres y 650 mujeres. Durante el período de seguimiento de 12 meses, hubo 790 casos de mortalidad por todas las causas. Se utilizó un análisis de regresión de Cox para validar la relación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Los pacientes con niveles más altos de ePWV tendían a tener una tasa de mortalidad por todas las causas más alta. Después del ajuste de múltiples factores, un aumento en ePWV se asoció positivamente con la tasa de mortalidad por todas las causas (HR=1,17, intervalo de confianza [IC] del 95%: 1,12-1,22). En comparación con el tercil más bajo, la HR ajustada por múltiples variables y el IC del 95% para el tercil más alto de ePWV fueron 1,81 (IC del 95%: 1,45-2,27)... (AU)

Background Arteriosclerosis has been proven to be a risk factor for the development of heart failure and readmission. ePWV is a novel non-invasive and simple indicator of arterial stiffness, and this study aims to investigate its relationship with all-cause mortality rate in patients with heart failure. Methods This study is a cohort study that included 1272 patients with heart failure from NHANES data from 1999 to 2018. The ePWV was divided into three groups, and the cumulative mortality rate of heart failure patients was calculated using KM survival curves. The relationship between ePWV and all-cause mortality rate in heart failure patients was represented by a smoothed curve fitting. COX regression analysis was used to assess the association between ePWV and all-cause mortality rate in heart failure patients. Results The average age of the study population was 67.8±12.6 years, with 862 males and 650 females. During the 12-month follow-up period, there were 790 cases of all-cause mortality. Cox regression analysis was used to validate the relationship between ePWV and all-cause mortality rate in patients with heart failure. Patients with higher levels of ePWV tended to have a higher all-cause mortality rate. After adjustment for multiple factors, an increase in ePWV was positively associated with all-cause mortality rate (HR=1.17, 95% confidence interval [CI]: 1.12-1.22). Compared to the lowest tertile, the multivariable-adjusted HR and 95%CI for the highest tertile of ePWV were 1.81 (95%CI: 1.45-2.27). Additionally, a smoothed curve fitting was used to observe the relationship between ePWV and mortality rate, where the curve demonstrated a positive correlation between ePWV and all-cause mortality rate. Furthermore, KM survival curves indicated that all-cause mortality rate increased with the increase in ePWV. Subgroup analysis suggested a correlation between ePWV and mortality rate... (AU)

[Nutritional status of 15 children with progeria].

Objective: To analyze the nutritional status of progeria, and to provide reference for scientific nutritional management of progeria. Methods: This cross-sectional study included 15 children with progeria who were treated at Children's Hospital, Zhejiang University School of Medicine, between April 2022 and May 2023. Data of medical history, physical examination, laboratory tests, dietary survey and body composition were collected and analyzed. Results: Among 15 patients there were 7 males and 8 females, aged 7.8 (2.3, 10.8) years. Twelve of the 15 patients exhibited signs of malnutrition. A 24-hour dietary survey was carried out in 14 of them. The daily energy intake of 11 cases was below recommended levels. Carbohydrate intake was insufficient in 10 cases, protein intake was insufficient in 7 cases, and fat intake was insufficient in 12 cases. Deficiencies in calcium, magnesium, iron and zinc were noted in 13, 13, 9 and 10 cases, respectively. Body composition was determined by dual-energy X-ray absorptiometry in 8 cases, and the bone mineral density was below average in 5 of them. Conclusions: Malnutrition, characterized by reduced energy intake, micronutrient deficiencies, and alteration in body composition, is prevalent in children with progeria. Regular routine nutritional assessment and proper interventions may benefit their long-term health status.

Targeted long-read sequencing for comprehensive detection of CYP21A2 mutations in patients with 21-hydroxylase deficiency.

BACKGROUND: 21-Hydroxylase deficiency (21-OHD) is caused by pathogenic CYP21A2 variations. CYP21A2 is arranged in tandem with its highly homologous pseudogene CYP21A1P; therefore, it is prone to mismatch and rearrangement, producing different types of complex variations. There were few reports on using only one method to detect different CYP21A2 variants simultaneously. AIMS: Targeted long-read sequencing method was used to detect all types of CYP21A2 variants in a series of patients with 21-OHD. METHODS: A total of 59 patients with 21-OHD were enrolled from Peking Union Medical College Hospital. Long-range locus-specific PCR and long-read sequencing (LRS) were performed to detect the pathogenic variants in CYP21A2. RESULTS: Copy-number variants of CYP21A2 were found in 25.4% of patients, including 5.1% with 3 copies of CYP21A2, 16.9% with 1 copy of CYP21A2, and 3.4% with 0 copy of CYP21A2. The remaining 74.6% of patients had 2 copies of CYP21A2. Pathogenic variants were identified in all 121 alleles of 59 patients. Specifically, single-nucleotide variants and small insertions/deletions (< 50 bp) were detected in 79 alleles, of which conversed from CYP21A1P were detected in 63 alleles, and rare variants were found in the other 16 alleles. Large gene conversions (> 50 bp) from pseudogene were detected in 10 alleles, and different chimeric genes (CYP21A1P/CYP21A2 or TNXA/TNXB) formed by large deletions were detected in 32 alleles. Of all variants, p.I173N was the most common variant (19.0%). CONCLUSIONS: Our study demonstrated that targeted long-read sequencing is a comprehensive method for detecting CYP21A2 variations, which is helpful for genetic diagnosis in 21-OHD patients.

Energetic Electron Precipitation Driven by Electromagnetic Ion Cyclotron Waves from ELFIN's Low Altitude Perspective.

We review comprehensive observations of electromagnetic ion cyclotron (EMIC) wave-driven energetic electron precipitation using data collected by the energetic electron detector on the Electron Losses and Fields InvestigatioN (ELFIN) mission, two polar-orbiting low-altitude spinning CubeSats, measuring 50-5000 keV electrons with good pitch-angle and energy resolution. EMIC wave-driven precipitation exhibits a distinct signature in energy-spectrograms of the precipitating-to-trapped flux ratio: peaks at >0.5 MeV which are abrupt (bursty) (lasting ∼17 s, or ΔL∼0.56) with significant substructure (occasionally down to sub-second timescale). We attribute the bursty nature of the precipitation to the spatial extent and structuredness of the wave field at the equator. Multiple ELFIN passes over the same MLT sector allow us to study the spatial and temporal evolution of the EMIC wave - electron interaction region. Case studies employing conjugate ground-based or equatorial observations of the EMIC waves reveal that the energy of moderate and strong precipitation at ELFIN approximately agrees with theoretical expectations for cyclotron resonant interactions in a cold plasma. Using multiple years of ELFIN data uniformly distributed in local time, we assemble a statistical database of ∼50 events of strong EMIC wave-driven precipitation. Most reside at L∼5-7 at dusk, while a smaller subset exists at L∼8-12 at post-midnight. The energies of the peak-precipitation ratio and of the half-peak precipitation ratio (our proxy for the minimum resonance energy) exhibit an L-shell dependence in good agreement with theoretical estimates based on prior statistical observations of EMIC wave power spectra. The precipitation ratio's spectral shape for the most intense events has an exponential falloff away from the peak (i.e., on either side of ∼1.45 MeV). It too agrees well with quasi-linear diffusion theory based on prior statistics of wave spectra. It should be noted though that this diffusive treatment likely includes effects from nonlinear resonant interactions (especially at high energies) and nonresonant effects from sharp wave packet edges (at low energies). Sub-MeV electron precipitation observed concurrently with strong EMIC wave-driven >1 MeV precipitation has a spectral shape that is consistent with efficient pitch-angle scattering down to ∼ 200-300 keV by much less intense higher frequency EMIC waves at dusk (where such waves are most frequent). At ∼100 keV, whistler-mode chorus may be implicated in concurrent precipitation. These results confirm the critical role of EMIC waves in driving relativistic electron losses. Nonlinear effects may abound and require further investigation.

The reinfection threshold, revisited.

One mode by which infection-derived immunity fails is when recovery leads to a reduced but nonzero risk of reinfection. This type of partial protection is called leaky immunity with the degree of leakiness quantified by the relative probability a previously infected individual will get infected upon exposure compared to a naively susceptible individual. Previous authors have defined the reinfection threshold, which occurs when the basic reproduction number equals the inverse of the leakiness, however, there has been some debate about whether or not this is a real threshold. Here we show how the reinfection threshold relates to two important occurrences: (1) the point at which the endemic equilibrium changes from being a stable spiral to a stable node, and (2) the point at which the rate of change of the prevalence increases the most relative to leakiness. When the recovery period is short relative to the average lifetime then both occurrences are close to the reinfection threshold. We show how these results are related to the reinfection threshold found in other models of imperfect immunity. To further demonstrate the significance of this threshold in modeling, we conducted a simulation study to evaluate some of the consequences the reinfection threshold might have in parameter estimation and modeling. Using specific parameter values chosen to reflect an acute infection, we found that the basic reproduction number values larger than that of the reinfection threshold value were less identifiable than those below the threshold.

[Mechanism study of platelet derived growth factor receptor alpha on the bidirectional differentiation regulation of glioma-associated oncogene homolog 1-positive mesenchymal stem cells in mice].

Objective: To investigate the role of platelet derived growth factor receptor alpha (PDGFRα) on bidirectional differentiation of glioma-associated oncogene homolog 1-positive mesenchymal stem cells (Gli1+-MSC). Methods: Breeding double reporter transgenic mice ROSAmT/mG/Gli1-CreERt2/PDGFRαfl (Experimental group) and ROSAmT/mG/Gli1-CreERt2 (Control group), 20 mice in each of the two groups at four weeks of age were selected, MSC were isolated from the mouse aortic epithelium. After tamoxifen inducement, the two groups of Gli1+-MSC were screened by green fluorescent protein (GFP) labeling and flow cytometry sorting. PDGFRα was conditionally knocked out in the experimental group, and the control group Gli1+-MSC expressed PDGFRα normally. The two groups of Gli1+-MSC were subjected to adipogenic induction and fibrogenic induction, the Western blotting was performed to detect PDGFRα, adipocyte markers [perilipin and CCAAT/enhancer binding protein alpha (C/EBPα)] and fibrogenic markers [alpha smooth muscle actin (α-SMA) and fibroblast-specific protein 1 (FSP-1)] and semi-quantitative analysis was performed. The degree of cellular adipose differentiation after bidirectional induction of Gli1+-MSC in both groups was observed by oil red O staining and analyzed semi-quantitatively. Results: After tamoxifen induction, Gli1+-MSC could be accurately isolated from flow cytometry by GFP labeling. Via adipogenic differentiation, the expression of PDGFRα in the experimental group (0.017±0.002) was significantly lower than that in the control group (0.184±0.012) (t=25.48，P=0.002). The protein expressions of perilipin (3.138±0.414) and C/EBPα (3.565±0.289) were significantly higher than those in the control group (2.312±0.218 and 2.179±0.103, respectively) (t=6.21，P=0.025；t=6.69，P=0.022). Thus, the knock-out of PDGFRα enhanced the adipogenic differentiation ability of Gli1+-MSC. After fibrogenesis induction, the protein expressions of PDGFRα, α-SMA and FSP-1 in the experimental group (0.030±0.001, 0.932±0.177 and 0.276±0.020, respectively) were significantly lower than those in the control group (0.439±0.006, 1.352±0.170 and 0.835±0.097, respectively) (t=149.40, P<0.001; t=66.38,P<0.001; t=11.41,P<0.08). This suggested that the knock-out of PDGFRα significantly inhibited Gli1+-MSC differentiation toward fibroblasts. After bidirectional induction, significantly less adipocyte formation was seen in the control group and more in the experimental group. Quantitative analysis showed that the amount of oil red O staining in the experimental group (0.461±0.042) was significantly higher than that in the control group (0.017±0.007) after bidirectional induction (t=23.20, P<0.01). Conclusions: PDGFRα plays an important role in the regulation of bidirectional differentiation of vascular adventitial Gli1+-MSC.

CCDC3 Gene Regulates the Proliferation of Breast Cancer Cells.

We studied the effect of CCDC3 on the viability of human breast cancer cell line MDA-MB-231. The levels of CCDC3 mRNA and the corresponding protein in MDA-MB-231, MCF-7, T-47D, and HCC1937 cell lines were measured by reverse transcription quantitative real-time PCR and Western blotting. Since MDA-MB-231 cells had higher expression of mRNA CCDC3 and CCDC3 protein, we used this cell line for transfection with small interfering RNA by lentivirus. Cell Counting Kit-8 and clone formation assay were used to detect the effects of CCDC3 knockdown on cell viability; flow cytometry was used to detect the effects of CCDC3 knockdown on cell apoptosis and cell cycle. In MDA-MB-231 cell line, the CCDC3 protein level was significantly down-regulated after CCDC3 knockdown in comparison with the control group (p<0.05). The cell viability and the number of clones in the CCDC3 knockdown group were significantly reduced (p<0.05), while the apoptosis rate significantly increased (p<0.05). Thus, after CCDC3 knockdown, cell viability is weakened in MDA-MB-231 cells, and cell apoptosis rate is increased. Therefore, CCDC3 gene is promising as a new candidate target for BC treatment.

[Clinical discussion on methimazole in the treatment of hyperthyroidism].

Methimazole is the most commonly used medication for hyperthyroidism with good effects and little adverse reactions. However, improper selection of initial dose will affect the efficacy, such as excessive dose is proven to various adverse reactions; insufficient dose can hardly achieve desired efficacy. Based on the literature and personal clinical experience, the author discusses the following clinical issues related to methimazole in the treatment of hyperthyroidism, including the selection of initial dose, dose adjustment and withdrawal of methimazole, drug therapy for patients with liver function injury, and management strategies for methimazole-related adverse reactions.

Insecticidal activity, Chemical Constituents of Trachyspermum ammi, Withania coagulans and Murraya koenigii ethanloic extracts against Bemisia tabaci.

Whitefly is one of the most widespread agricultural pests in the world. Essential oils might be used to control this insect in an environmentally responsible way. The fumigant, repellent, and anti-oviposition activity of ethanol-extracted essential oils of Trachyspermum ammi, Withania coagulans, and Murraya koenigii against Bemisia tabaci was investigated in this study. In the experiment, three essential oil concentrations (2.5 mg/mL, 5 mg/mL, and 10 mg/mL) were used. Trachyspermum ammi had the highest percentage of whitefly death in laboratory experiments due to its fumigant toxicity; the same tendency was found in contact toxicity and repellent effect. Mortality percent rises as the concentration of essential oil increases with bioassay time. As the concentration of essential oil grows with bioassay time, so does the mortality rate. The most adult whiteflies escaped from the treated plants' greenhouse due to the highest essential oil concentration. The greatest repellency was found with Trachyspermum ammi essential oil at 10 mg/mL. The essential oil had the greatest anti-oviposition efficacy against whiteflies. Trachyspermum ammi possessed the most potent anti-oviposition deterrent, followed by Withania coagulans in second place. Murraya koenigii finished third with moderate anti-oviposition, which affects the number of eggs produced in comparison to the control. As a consequence, these three oils might be used as an effective and environmentally acceptable bio-insecticide to control B. tabaci.