[Incidence and cause of abnormal cholesterol in children aged 2-18 years in a single center].

OBJECTIVE: To investigate the abnormality and distribution of plasma cholesterol levels in single-center hospitalized children. METHODS: The blood lipid levels of children aged 2-18 years who had blood lipid test results in Peking University First Hospital from June 2016 to June 2019 were etrospectively analyzed. Cholesterol oxidase method was used for total cholesterol, and high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were detected by clearance method. The counting data were compared with chi-square test. RESULTS: The survey had involved 11 829 children (7 087 were boys and 4 742 were girls). 1 822 (15.4%) children were with elevated total cholesterol, 1 371 (11.6%) children with elevated low-density lipoprotein cholesterol, and 2 798 (23.7%) children with high-density lipoprotein cholesterol reduction. The total number of the children with abnormal cholesterol levels was 4 427 (37.4%). Among the 7 835 children who visited hospital due to the disease not commonly inducing dyslipidemia, 731 (9.3%) had elevated TC, 561 (7.2%) had elevated LDL-C, 1 886 (24.1%) had decreased HDL-C, and 2 576 (32.9%) had abnormal cholesterol levels. Among the children with different diseases, the difference in the incidence of abnormal cholesterol was statistically significant. The top three main groups of the children with increased total cholesterol and low-density lipoprotein cholesterol were "dyslipidemia", "urinary tract disease", and "nutritional disease"; The top three main groups of the children with reduced high-density lipoprotein cholesterol were "respiratory diseases", "dyslipidemia", "hematological diseases and malignant tumors". Among the 1 257 blood li-pid test results sent by other departments, 300 cases had abnormal cholesterol levels (23.8%). Among them, there were 70 children with hypercholesterolemia (5.6%), 44 children with increased low-density lipoprotein cholesterol (3.5%), and 224 children with reduced high-density lipoprotein cholesterol (17.8%). There were 365 (4.6%) children with low-density lipoprotein cholesterol ≥140 mg/dL (3.6 mmol/L) who needed to further exclude familiar hypercholesterolemia among the children who visited hospitals due to the disease not commonly inducing dyslipidemia. CONCLUSION: Children in hospitals have a high incidence of cholesterol abnormalities. Doctors need to pay more attention to the cholesterol diagnosis and management regardless of the discipline, which not only helps to control secondary hypercholesterolemia, but also provides the possibility of detecting familial hypercholesterolemia in time.

Investigation of the Inhibitory Effect of Platycodin D in Human Transitional Cell Carcinoma Cell Line 5637.

Platycodin D is an active component isolated from Chinese herb Platycodonis radix with various pharmacological activities, such as antitussive, expectorant, anti-inflammatory, and analgesic effects. Interestingly, platycodin D also exerts anticancer effects against several types of cancer. However, few studies on the anti-tumour effects of platycodin against urinary bladder cancer have been reported. In this study, we explored the anti-tumour effect of platycodin D against human bladder cancer and its mechanisms in vitro and in vivo. We found that platycodin D had significant anti-proliferative effects on four types of cancer cells, especially the 5637 bladder cancer cell line, and exerted these effects by preventing cell cycle progression from G0/G1 to S phase, down-regulating Ki-67 and cyclin D1 protein expression and up-regulating P21 protein expression. Furthermore, platycodin D inhibited 5637 cell migration by decreasing twist-related protein 1 (Twist1) and matrix metallopeptidase 2 (MMP2) expression and exerted significant tumour-suppressive effects in tumour-bearing nude mice. Platycodin D also increased caspase-9, caspase-8, caspase-3, and p53 expression and decreased Bcl-2 expression in tumour tissues. Taken together, our results provide a theoretical basis for application of platycodin D in treating urinary bladder cancer.

An electromagnetic separation system for the enrichment of 39Ar.

An isotope enrichment system for 39Ar has been developed at the Institute of Modern Physics, which is designed to increase the abundance of 39Ar in the incident sample gas. With intense Ar+ beams produced by a 2.45 GHz electron cyclotron resonance ion source and a high mass resolution spectrometer system, Ar isotopes are evidently separated on the target plane and selectively collected by an Al target. The separated Ar isotopes have been identified on the target plane, which is consistent with the simulations. According to the recent cross-checked results with atom trap trace analysis, a high enrichment factor of 39Ar has been successfully achieved. This paper will present the design and test results of this system.

Collagenofibrotic glomerulopathy- report of a rare renal disease with serial biopsies.

INTRODUCTION: Collagenofibrotic glomerulopathy or collagen type-III glomerulopathy is a rare glomerular disease characterised by the deposition of type III collagen fibres in the subendothelial space and mesangium of the glomerulus. CASE REPORT: Here, we present a case of collagenofibrotic glomerulopathy in a 49-year-old Indian female, the first to be reported from Singapore. Renal biopsy showed PAS (periodic acid-Schiff), silver and Congo red negative, amorphous extracellular material that expanded mesangial and subendothelial regions. Such materials were strongly positive for anti-collagen III immunofluorescent staining. Under electron microscopy, the mesangial and some subendothelial regions were greatly expanded by abundant collagen fibres which were different from normal collagen III fibres in both appearance and periodicity. DISCUSSION: The availability of past renal biopsies for reference offered insight into disease progression. From the initial diagnosis of focal segmental glomerulosclerosis to eventually collagenofibrotic glomerulopathy over a time span of more than 10 years, this case highlights the gradual accumulation of collagen fibres in the glomeruli before classical features are apparent. It also emphasises the importance of electron microscopy in the diagnosis of this disease.

Racial difference in bioavailability of oral ibandronate between Caucasian and Taiwanese postmenopausal women.

Following 150 mg of oral ibandronate, Taiwanese females have greater serum and urine levels of this drug and bone resorption marker suppression than Caucasian women. These inter-ethnic differences seems to be partly explained by a 2.48-fold higher bioavailability of ibandronate in Taiwanese postmenopausal women. INTRODUCTION: Interethnic differences in the pharmacokinetics of oral ibandronate for osteoporosis are unknown. We compared the disposition of oral ibandronate between Caucasian and Taiwanese postmenopausal women. METHODS: Ibandronate 150 mg was administered to 35 Caucasian and 16 Taiwanese postmenopausal women in two separate phase 1 studies. Interethnic comparisons were performed to assess pharmacokinetic properties, including the area under the concentration-time curve (AUC), peak concentration (Cmax), elimination half-life, urinary drug recovery (Ae%), renal clearance (CLr), apparent total clearance (CL/F), and apparent volume of distribution (Vd/F). RESULTS: The mean AUC, Cmax, and Ae% were 2.41-, 1.69-, and 2.95-fold greater in the Taiwanese than in the Caucasian subjects, and the average CL/F and Vd/F were 2.48- and 2.46-fold smaller. There were no significant differences in mean CLr and half-life between both groups. As bisphosphonates are not biotransformed but are mainly excreted in the urine, the total body clearance is close to the CLr. These results suggested a larger bioavailability in the Taiwanese group which resulted in the differences in the CL/F and Vd/F. Multiple linear regression analysis demonstrated ethnicity influences of the pharmacokinetic properties after adjusting for the other variables. CONCLUSIONS: Bioavailability was largely responsible for the interethnic pharmacokinetic differences following oral administration of 150 mg ibandronate and seemed greater in the Taiwanese compared with the Caucasian subjects. Further dose-ranging studies are warranted to determine the optimal dosages of oral ibandronate in patients of Asian or Taiwanese ethnicity.

Serum fibroblast growth factor 23 and mineral metabolism in patients with euthyroid Graves' diseases: a case-control study.

This study investigated the alterations of mineral metabolism in patients with Graves' disease (GD) who achieved euthyroidism. They had higher fibroblast growth factor 23 (FGF23) and phosphorus as compared with healthy subjects. Serum FGF23 was negatively correlated with serum phosphorus. These indicated abnormal mineral metabolism even after 1.6 years of euthyroid status. INTRODUCTION: FGF23 is involved in the mineral homeostasis, especially the regulation of serum phosphorus. Graves' disease (GD) is associated with accelerated bone turnover, hyperphosphatemia, and elevated serum FGF23. Evidence suggested that serum FGF23 decreased after a 3-month treatment of GD. However, it remains unclear whether serum FGF23, serum phosphorus, and other markers of mineral metabolism will be normalized after euthyroid status achieved. METHODS: A total of 62 patients with euthyroid GD and 62 healthy control subjects were enrolled, and the median duration of euthyroid status was 1.6 years. Endocrine profiles including thyroid function test, autoantibodies, serum FGF23, and bone turnover markers were obtained and compared between the two groups. RESULTS: Euthyroid GD patients had significantly higher serum FGF23 and phosphorus, and lower 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH) levels as compared with the control group. Serum FGF23 was significantly and negatively correlated with phosphorus level after adjusted for age, gender, calcium, iPTH, and 25(OH)D in the euthyroid GD group. CONCLUSION: Serum phosphorus and FGF23 levels remain higher in GD patients even after euthyroid status has been achieved for a median of 1.6 years. Serum FGF23 was negatively correlated with serum phosphorus in euthyroid GD patients. Underlying mechanisms warrant further investigations. TRIAL REGISTRATION: Registration number: NCT01660308 and NCT02620085.

Expression pattern of estrogen receptor ß and its correlation with multidrug resistance in non-small cell lung cancer.

The aim of this work was to determine the expression of the ERß (estrogen receptor ß) and multidrug resistance, namely MDR1 (P-glycoprotein, P-gp), in 152 samples of non-small cell lung cancer. The expression pattern of ERß and MDR1 were assessed by the quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry. We also analyzed the correlation between ERß and MDR1 with clinical and pathological data. The co-expression pattern of ERß and individual MDR1 proteins was assessed by correspondence analysis and chi-squared tests. In the present study, we found that patients with tumor stage I-II showed higher ERß mRNA expression levels and decreased expression of ERß protein with increasing tumor grade, which is opposite to MDR1 expression. In addition, an opposite co-expression pattern of ERß and individual MDR1 proteins was also observed. In conclusion, the results can be used to better understand the expression control of MDR1 and may allow for the establishment of new cancer chemistry strategies that will control P-gp expression in NSCLC.

A Case Series of Asymptomatic Hemodialysis Catheter-Related Right Atrial Thrombi That Are Incidentally Detected Prior to Kidney Transplantation.

A hemodialysis (HD) catheter-related right atrial thrombus (RAT) is rarely encountered prior to kidney transplantation (KT) but necessitates a decision about whether to anticoagulate and/or delay the surgery. There is controversy surrounding the clinical implications of a RAT in this situation. It is sometimes considered fatal but other opinions consider it to be benign, especially when incidentally detected. We reviewed the clinical characteristics, management, and outcomes of a patient series with HD catheter-related RAT detected prior to KT and speculated on its clinical significance. Among 3677 cases of KT performed on 3607 patients between January 1997 and September 2015 in our single tertiary center, 11 cases of HD catheter-related RAT detected on transthoracic echocardiography (TTE) prior to KT were included for analysis. The average maximal diameter of the RAT was 23.2 ± 16.3 (SD in mm) and 9 (81.8%) of these 11 patients had no symptoms associated with the RAT. Four patients (36.3%) had their catheters replaced, 5 patients (45.5%) had their catheters removed, and the catheters were maintained in the remaining 2 patients (18.2%). Six patients (54.5%) were anticoagulated with either heparin or warfarin. However all 11 patients had a successful KT suggesting that a HD catheter-related RAT incidentally detected prior to this surgery may not be as serious as previously considered and should not be a reason for delaying the transplantation.

MIG-6 negatively regulates STAT3 phosphorylation in uterine epithelial cells.

Endometrial cancer is the most common malignancy of the female genital tract. Progesterone (P4) has been used for several decades in endometrial cancer treatment, especially in women who wish to retain fertility. However, it is unpredictable which patients will respond to P4 treatment and which may have a P4-resistant cancer. Therefore, identifying the mechanism of P4 resistance is essential to improve the therapies for endometrial cancer. Mitogen-inducible gene 6 (Mig-6) is a critical mediator of progesterone receptor (PGR) action in the uterus. In order to study the function of Mig-6 in P4 resistance, we generated a mouse model in which we specifically ablated Mig-6 in uterine epithelial cells using Sprr2f-cre mice (Sprr2fcre+Mig-6f/f). Female mutant mice develop endometrial hyperplasia due to aberrant phosphorylation of signal transducers and activators of transcription 3 (STAT3) and proliferation of the endometrial epithelial cells. The results from our immunoprecipitation and cell culture experiments showed that MIG-6 inhibited phosphorylation of STAT3 via protein interactions. Our previous study showed P4 resistance in mice with Mig-6 ablation in Pgr-positive cells (Pgrcre/+Mig-6f/f). However, Sprr2fcre+Mig-6f/f mice were P4-responsive. P4 treatment significantly decreased STAT3 phosphorylation and epithelial proliferation in the uterus of mutant mice. We showed that Mig-6 has an important function of tumor suppressor via inhibition of STAT3 phosphorylation in uterine epithelial cells, and the antitumor effects of P4 are mediated by the endometrial stroma. These data help to develop a new signaling pathway in the regulation of steroid hormones in the uterus, and to overcome P4 resistance in human reproductive diseases, such as endometrial cancer.

Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation.

Ferroptosis is a form of regulated non-apoptotic cell death that has been implicated in several disease contexts. A better understanding of the ferroptotic death mechanism could lead to the development of new therapeutics for degenerative diseases, and a better understanding of how to induce ferroptosis in specific tumor contexts. We performed an unbiased genome-wide siRNA screen to find genetic suppressors of ferroptosis. We determined that loss of CARS, the cysteinyl-tRNA synthetase, suppresses ferroptosis induced by erastin, which inhibits the cystine-glutamate antiporter known as system xc(-). Knockdown of CARS inhibited erastin-induced death by preventing the induction of lipid reactive oxygen species, without altering iron homeostasis. Knockdown of CARS led to the accumulation of cystathionine, a metabolite on the transsulfuration pathway, and upregulated genes associated with serine biosynthesis and transsulfuration. In addition, inhibition of the transsulfuration pathway resensitized cells to erastin, even after CARS knockdown. These studies demonstrate a new mechanism of resistance to ferroptosis and may lead to strategies for inducing and suppressing ferroptosis in diverse contexts.

Long-term Outcomes of ABO-Incompatible Living Donor Kidney Transplantation: A Comparative Analysis.

BACKGROUND: Although ABO-incompatible kidney transplantation has become more common due to organ shortage, few studies on long-term outcomes have been performed in the Korean population. METHODS: A retrospective review of medical records was conducted for individuals who underwent living donor kidney transplantation at Asan Medical Center from February 2009 to January 2012. RESULTS: A total of 469 patients were included; the mean age was 42.8 ± 11.8 years, and the median follow-up period was 45 (range, 1-65) months. ABO-incompatible recipients (73) were compared with ABO-compatible patients (396). Patient survival was similar between the ABO-incompatible group (97.3% and 95.9% at 1 and 3 years) and the ABO-compatible group (99.0% and 98.5% at 1 and 3 years; P = .136). Death-censored graft survival was also comparable between groups (98.6% vs 99.7% at 1 year; 98.6% vs 98.7% at 3 years; P = .386). Graft function, acute rejection, and postoperative complications were not significantly different between groups. Additionally, high body mass index and multiple human leukocyte antigen mismatches were significant risk factors for acute rejection (OR: 1.08, 95% CI: 1.01-1.16, P = .033; and OR: 1.20, 95% CI: 1.02-1.40, P = .025, respectively). CONCLUSION: ABO-incompatible kidney transplantation could be a safe option when ABO-compatible donors are not available.

ApoE and S-100 expression and its significance in the brain tissue of rats with focal contusion.

This study explored the effect of focal cerebral contusion on the expression of ApoE and S-100, and its significance in determining the time of brain injury. Based on a rat model of cerebral contusion, immunohistochemistry was used to analyze the expressions of S-100 and ApoE at different time points after injury. Thirty minutes following cerebral contusion, ApoE protein expression was significantly increased in cortex neurons (P < 0.01), and S-100 protein expression was significantly (P < 0.001) elevated 2 h after cerebral contusion. Over time, the number of ApoE and S-100 positively expressing cells gradually increased. Three days after injury, ApoE was widely distributed throughout the tissue and the number of ApoE-positive cells and staining intensity reached a peak. ApoE expression decreased after this time point. Five days after cerebral contusion, the number of S-100-positive cells reached a peak level of expression higher than that in the control group. Our data demonstrate that the expression of ApoE and S-100 correlated with the progression of focal cerebral contusion. This suggests that both proteins may serve as effective biomarkers of focal cerebral contusions.

Induction of apoptosis in human cervical carcinoma Hela cells with active components of Menispermum dauricum.

Menispermum dauricum DC possesses a wide range of pharmacological effects. In this study, the mechanism of apoptosis induced by active components of M. dauricum was investigated in the human cervical carcinoma HeLa cell line. HeLa cells were treated with different M. dauricum concentrations over different time periods. The proliferation-inhibitory rate and cytotoxic effect of HeLa cells were measured by using the methyl thiazolyl tetrazolium (MTT) assay, and the apoptotic rate was detected by flow cytometry. Expressions of caspase-9, caspase-8, caspase-3, Bcl-2, and Fas proteins, in the apoptotic pathway, and the expression of nuclear factor-kappa B (NF-κB) were detected by SP immunocytochemistry. The MTT assay showed that active components of M. dauricum could significantly inhibit the growth of HeLa cells in a dose- and time-dependent manner (P<0.01). The Sub-Gl peak was found by flow cytometry, and the maximal apoptosis rate was 24.93%. Immunocytochemistry showed that after treatment with M. dauricum, the expressions of caspase-8, caspase-9, caspase-3, Fas protein, and NF-κB all increased, and the expression of the Bcl-2 protein decreased, with significant differences relative to the control group (P<0.01). Apoptosis in HeLa cells could be induced by active components of M. dauricum through the NF-κB signal transduction pathway and the caspase pathway, which was related to the downregulation of Bcl-2 expression and the upregulation of Fas expression.

Ultrafast response sensor to formaldehyde gas based on metal oxide.

Thick film semiconductor gas sensors based on indium oxide were fabricated on Si substrate. The sensing materials on Si substrate were characterized using optical microscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM), and so on. They were very fine and uniform and we found out that particle sizes were about 20~30 nm through XRD analysis. Gas responses of fabricated sensors were measured in a chamber where gas flow was controlled by mass flow controller (MFC). Their resistance changes were monitored in real time by using data acquisition board and personal computer. Gas response characteristics were examined for formaldehyde (HCHO) gas which was known as the cause of sick building syndrome. Particularly, the sensors showed responses to formaldehyde gas at sub ppm (cf, standard of natural environment in building is about 80 ppb by ministry of environment in Korea), as a function of operating temperatures and gas concentrations. Also, we investigated sensitivity, repetition, selectivity, response speed and reproducibility of the sensors. The lowest detection limit is HCHO 25 ppb and sensitivity at 800 ppb is over 25% at 350 °C operating temperature. The response time (8 s) and recovery time (15 s) to HCHO gas at 200 ppb were very fast compared to other commercial products in flow type measurement condition. Repetition measurement was very good with ±3% in full measurement range. The fabricated metal oxide gas sensor showed good performance to HCHO gas and proved that it could be adaptable to indoor environment in building.

Clinical courses of renal transplant recipients with high BK viremia.

OBJECTIVE: We sought to investigate the clinical courses of renal transplant recipients with plasma BK viral loads >10(4) copies/mL. METHODS: A single-center retrospective review was performed of 88 kidney transplant patients in whom high BK viremia (defined as plasma BKV load >10(4) copies/mL) was detected more than once from January 1, 2004, to December 31, 2011. RESULTS: At the time of transplantation, the mean recipient and donor ages were 44.5 ± 11.1 and 43.9 ± 11.3 years, respectively, and 59 subjects (67.0%) were male. The median times to first BK positivity and high BK viremia after transplantation were 44 and 136 days, respectively. Within 3 months after transplantation, we detected, 56 cases of high BK viremia (63.6%). The mean duration of high BK viremia was 8.2 ± 7.7 months. When plasma BKV load was first >4 logs, the mean log BKV load was 5.50 ± 1.11 log copies/mL, which rose to a maximum of 5.82 ± 1.11. At these times, mean serum creatinine concentrations were 1.67 ± 0.79 and 2.64 ± 2.78 mg/dL, respectively. There were 31 cases (35%) of biopsy-proven BK nephropathy patients among 51 (58%) biopsies. Treatment modalities included discontinuation or dose reduction of mycophenolic acid drugs (n = 68) and switch from tacrolimus to cyclosporine (n = 9), cidofovir (n = 9), and leflunomide (n = 3). Based on the serum creatinine elevation after high BK viremia, patients were divided into group 1 (n = 27; 30.1%), whose maximal creatinine change was <0.5 mg/dL, and group 2, with a greater alteration. On multivariate logistic regression analysis, the maximal plasma BK viral load was significantly associated with a greater serum creatinine elevation (P < .001). CONCLUSIONS: High BK viremia mostly occurred within 3 months after kidney transplantation. About 30% of renal allograft recipients with high BK viremia maintained stable renal function. Maximal plasma BK viral load was the only independent risk factor for high serum creatinine elevation.

Identification of a novel HLA-B allele, B*07:162, in a Taiwanese individual.

The new allele, HLA-B*07:162, is identical to HLA-B*07:12 in exon 2 but has a non-synonymous substitution at position 419 (A to C) in exon 3.