Association between chinese visceral adiposity index and risk of kidney stones in a health screening population: an ultrasonography based cross-sectional study.

BACKGROUND: Obesity is an important risk factor for kidney stones(KS). Chinese Visceral Adiposity Index (CVAI), as a specific indicator for visceral obesity in the Chinese population, can more accurately assess the visceral fat content in Chinese individuals compared to Visceral Adiposity Index (VAI). However, the association between CVAI and risk for KS has not been studied. METHODS: A total of 97,645 participants from a health screening cohort underwent ultrasound examinations for the diagnosis of kidney stones, along with measurements of their CVAI. Logistic regressions were utilized to determine the relationship between different quartiles of CVAI and the incidence of kidney stones. Simultaneously, subgroup analysis and the computation of dose-response curves were employed to pinpoint susceptible populations. RESULTS: Among the participants, 2,888 individuals (3.0%) were diagnosed with kidney stones. The mean CVAI values ± standard deviation for the four groups were: Q1 (18.42 ± 19.64), Q2 (65.24 ± 10.39), Q3 (98.20 ± 9.11), and Q4 (140.40 ± 21.73). In the fully adjusted multivariable model, CVAI was positively correlated with urolithiasis (OR = 1.001; 95% CI = 1.000, 1.002). Compared with the first quartile of CVAI, the population in the fourth quartile of CVAI had a higher prevalence of kidney stones (OR = 1.231; 95% CI = 1.066, 1.415). Through subgroup analysis, a positive correlation between CVAI and the risk of kidney stones was found in non-smokers (OR = 1.001, 95%CI:1.000, 1.002), non-drinkers (OR = 1.001, 95%CI:1.000, 1.002), non-hypertensive subgroups (OR = 1.003, 95%CI:1.002, 1.003), and non-diabetes subgroups (OR = 1.001, 95%CI:1.000, 1.002). CONCLUSION: The findings suggest that CVAI could be a reliable and effective biomarker for assessing the potential risk of kidney stone prevalence, with significant implications for the primary prevention of kidney stones and public health.

Clinical and genetic analysis of a case of O'Donnell-Luria-Rodan syndrome manifesting as growth retardation. / 以生长发育迟缓为表现的1例O'Donnell-Luria-Rodanç»¼åˆå¾ä¸´åºŠä¸Žé—ä¼ å­¦ç‰¹å¾åˆ†æž.

O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant genetic disorder caused by mutations in the KMT2E (lysine methyltransferase 2E) gene. The Third Xiangya Hospital of Central South University admitted a 12-year and 9-month-old male patient who presented with growth retardation, intellectual disability, and distinctive facial features. Peripheral blood was collected from the patient, and DNA was extracted for genetic testing. Chromosome karyotyping showed 46XY. Whole-exome sequencing and low-coverage massively parallel copy number variation sequencing (CNV-seq) revealed a 506 kb heterozygous deletion in the 7q22.3 region, which includes 6 genes, including KMT2E. The patient was diagnosed with ODLURO syndrome. Both the patient's parents and younger brother had normal clinical phenotypes and genetic test results, indicating that this deletion was a de novo mutation. The clinical and genetic characteristics of this case can help increase clinicians' awareness of ODLURO syndrome.

p120-catenin suppresses proliferation and tumor growth of oral squamous cell carcinoma via inhibiting nuclear phospholipase C-γ1 signaling.

p120-catenin (p120) serves as a stabilizer of the calcium-dependent cadherin-catenin complex and loss of p120 expression has been observed in several types of human cancers. The p120-dependent E-cadherin-ß-catenin complex has been shown to mediate calcium-induced keratinocyte differentiation via inducing activation of plasma membrane phospholipase C-γ1 (PLC-γ1). On the other hand, PLC-γ1 has been shown to interact with phosphatidylinositol 3-kinase enhancer in the nucleus and plays a critical role in epidermal growth factor-induced proliferation of oral squamous cell carcinoma (OSCC) cells. To determine whether p120 suppresses OSCC proliferation and tumor growth via inhibiting PLC-γ1, we examined effects of p120 knockdown or p120 and PLC-γ1 double knockdown on proliferation of cultured OSCC cells and tumor growth in xenograft OSCC in mice. The results showed that knockdown of p120 reduced levels of PLC-γ1 in the plasma membrane and increased levels of PLC-γ1 and its signaling in the nucleus in OSCC cells and OSCC cell proliferation as well as xenograft OSCC tumor growth. However, double knockdown of p120 and PLC-γ1 or knockdown of PLC-γ1 alone did not have any effect. Immunohistochemical analysis of OSCC tissue from patients showed a lower expression level of p120 and a higher expression level of PLC-γ1 compared with that of adjacent noncancerous tissue. These data indicate that p120 suppresses OSCC cell proliferation and tumor growth by inhibiting signaling mediated by nuclear PLC-γ1.

Long-Term Bioavailability of Single Doses of Intramuscular Vitamin D2.

OBJECTIVE: We sought to determine the long-term bioavailability of single doses of intramuscular (IM) vita-min D2 (D2) in healthy adults. METHODS: Forty healthy volunteers with hypovitaminosis D received a single dose of 200,000, 400,000, or 600,000 IU intramuscular D2 or no treatment. Levels of 25-hydroxyvitamin D2 (25[OH]D2) and 25-hydroxyvitamin D3 (25[OH]D3) in serum were measured by liquid chromatography-tandem mass spectrometry. Vitamin D binding protein (DBP) and intact parathyroid hormone (iPTH), bone turnover markers (BTMs), and serum and urinary calcium were also measured. RESULTS: After a single dose of D2 injection, the level of 25(OH)D2 increased slowly and reached a plateau at 8 weeks. The plateau remained stable for 12 weeks. The mean increase in 25(OH)D2 was 6.8, 9.6, or 15.6 ng/mL after injection of 200,000 IU, 400,000 IU, or 600,000 IU D2. Although endogenous 25(OH)D3 levels were reduced by IM D2, the total 25(OH)D levels increased by 5.0, 7.0, or 10.3 ng/mL in average after injection of 200,000 IU, 400,000 IU, or 600,000 IU D2. The iPTH levels were also decreased by IM D2. However, levels of serum calcium, BTMs, and DBP and urinary calcium were not altered by IM D2. CONCLUSION: A single dose of 200,000 IU, 400,000 IU, or 600,000 IU IM D2 raises total 25-hydroxyvitamin D levels by 5.0, 7.0, or 10.3 ng/mL on average for at least 12 weeks and reduces iPTH and endogenous 25(OH)D3 levels without affecting levels of serum calcium, BTMs, DBP, and urinary calcium.

Effect of Tannic Acid on Nutrition and Activities of Detoxification Enzymes and Acetylcholinesterase of the Fall Webworm (Lepidoptera: Arctiidae).

Plant tannins, polyphenolic plant secondary metabolites are involved in important chemical defense processes in plants. In this study, tannic acid was used as the standard of plant tannins to determine the effects on nutritional indices and activities of glutathione S-transferases (GSTs), cytochrome P450 monooxygenase (CYP450), carboxylesterase (CarE), and acetylcholinesterase (AChE) in fourth-instar larvae of Hyphantria cunea (Drury) by feeding on an artificial diet containing tannic acid under different treatments. We found that tannic acid significantly affected the digestive capacity and food utilization rate of H. cunea larvae. A tannic acid concentration of less than 2.0% promoted feeding and the utilization of undesirable food by H. cunea larvae, while inhibitory effects were observed at high concentrations (>2.5%). Tannic acid had a significant effect on the activity of detoxification enzymes and AChE in H. cunea larvae in concentration-dependent and time-dependent manners (P < 0.05). These results provide new insights into the potential mechanisms underlying detoxification in H. cunea larvae against tannic acid in host plants.

Regulation of 25-hydroxyvitamin D-1-hydroxylase and 24-hydroxylase in keratinocytes by PTH and FGF23.

Renal 25-hydroxyvitamin D-1α-hydroxylase (1αOHase, CYP27B1) and 24-hydroxylase (24OHase, CYP24A1) are tightly regulated. However, little is known about the regulation of 1α(OH)ase and 24(OH)ase in extrarenal tissue such as the epidermis. This study was to determine the roles of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF 23) in the regulation of 1α(OH)ase and 24(OH)ase in epidermal keratinocytes as well as epidermal keratinocyte proliferation and differentiation. The results showed that PTH increased the protein level of 1α(OH)ase in human epidermal keratinocyte cell line HaCaT, but had no effect on the level of 24(OH)ase. The effect of PTH on 1α(OH)ase was blocked by the PKC inhibitor. Treatment with FGF23 decreased mRNA and protein levels of 1α(OH)ase and increased mRNA and protein levels of 24(OH)ase in HaCaT cells. The effect of FGF23 on 1α(OH)ase and 24(OH)ase was blocked by the mitogen-activated protein kinase/extracellular regulated protein kinase (MAPK/ERK) inhibitor. In addition, treatment with PTH enhanced levels of differentiation markers including keratin 1, involucrin, loricrin, and filaggrin but reduced levels of BrdU incorporation in HaCaT cells. These effects were inhibited by the PKC inhibitor. FGF23 enhanced proliferation of HaCaT cells, but reduced levels of early differentiation markers including keratin 1 and involucrin and enhanced levels of the later differentiation markers including loricrin and filaggrin. These results suggest that PTH stimulates 1α(OH)ase expression and differentiation of HaCaT cells and inhibits proliferation via PKC. The data also suggest that FGF23 inhibits 1α(OH)ase expression and stimulates 24(OH)ase expression via MAPK/ERK. In addition, FGF23 enhances proliferation and late differentiation and inhibits early differentiation of HaCaT keratinocytes.

Successful treatment of a giant ovarian cyst by levothyroxin in a young adult woman: A case report.

Ovarian cysts are one of the most common gynecologic affections for females. The most effective therapy is surgery, but not for all conditions. An 18-year-old woman was referred to our hospital because of menstruation disorder and abdominal distension. Ultrasound and computer tomography of the abdomen revealed a giant ovarian cyst. Magnetic resonance imaging revealed profound pituitary enlargement. Laboratory studies showed severe hypothyroidism, mild anemia, hyperlipidemia, hyperprolactinemia and an elevated level of cancer antigen-125. Regression of the giant ovarian cyst and pituitary enlargement was observed after a 5-month levothyroxine replacement therapy. Thus, for patients with ovarian cysts, hypothyroidism should be taken into account. Making correct diagnosis would avoid unnecessary surgery.

Performance evaluation of two immunoassays for 25-hydroxyvitamin D.

Although immunoassays in measuring 25-hydroxyvitamin D [25(OH)D] have been improved recently, relatively large differences are still seen between results of 25(OH)D measured by immunoassays and by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In the present studies, we compared two immunoassays with LC-MS/MS for measuring 25(OH)D concentrations. Concentrations of 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] in serum samples from 59 healthy subjects were measured by two immunoassays including Siemens ADVIA Centaur Vitamin D Total (Centaur) and Roche Elecsys Vitamin D Total (Elecsys) and LC-MS/MS. To determine the cross reactivity of Elecsys and Centaur toward 25(OH)D2, a dosage of 200,000 IU vitamin D2 was given after first sampling. Serum samples were obtained 30 days later and concentrations of 25(OH)D2 and 25(OH)D3 were measured again. The results showed poor agreement between the immunoassays and LC-MS/MS in 25(OH)D2 and 25(OH)D3 measurements. The percentage of 25(OH)D2 cross-reactivity was 45.3% for Centaur and 41.2% for Elecsys and there was no significant difference between Centaur and Elecsys. In conclusion, Centaur and Elecsys perform unsatisfactorily in measuring 25(OH)D levels, especially for 25(OH)D2 cross-reactivity. Therefore, clinicians need to be aware of the underestimation of vitamin D status when using these immunoassays for measuring individuals supplemented with vitamin D2.

Identification of FOXM1 and CXCR4 as key genes in breast cancer prevention and prognosis after intermittent energy restriction through bioinformatics and functional analyses.

We explored potential biomarkers and molecular mechanisms regarding breast cancer (BC) risk reduction after intermittent energy restriction (IER) and further explored the association between IER and BC prognosis. We identified differentially expressed genes (DEGs) in breast tissues before and after IER by analyzing the expression profile from GEO. Then, enrichment analysis was used to identify important pathways of DEGs and hub genes were selected from PPI network. After that, GEPIA, ROC, and KM plotter were used to explore the preventive and prognostic value of hub genes. It was found that FOXM1 and CXCR4 were highly expressed in BC tissues and associated with the worse prognosis. FOXM1 and CXCR4 were down-regulated after IER , which meant that FOXM1 and CXCR4 might be the most important key genes for reducing the risk and improving prognosis of BC after IER . ROC curve indicated that FOXM1 and CXCR4 also had the predictive value for BC. Our study contributed to a better understanding of the specific mechanisms in protective effects of IER on BC and provided a new approach to improve the prognosis of BC, which might provide partial guidance for the subsequent development of more effective treatments and prevention strategies.

C/EBPß mediates anti-proliferative effects of 1,25(OH)2D on differentiated thyroid carcinoma cells.

Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy and highly expresses the receptor for 1,25-dihydroxyvitamin D (1,25(OH)2D). However, it is unclear whether 1,25(OH)2D regulates DTC proliferation and differentiation. Here, we found that 1,25(OH)2D3 inhibited proliferation but not differentiation of the DTC cells. Notably, CYP27B1was elevated in DTC cells and 25-hydroxyvitamin D3 (25(OH)D3) reduced DTC cell proliferation. Knockdown of VDR did not affect the anti-proliferative effects of 1,25(OH)2D3. However, knockdown of CCAAT enhancer-binding protein ß (C/EBPß)abolished 1,25(OH)2D3-suppressed DTC cell proliferation. In addition, 1,25(OH)2D3 induced phosphorylation and translocation of C/EBPßto the nucleus from the cytoplasm. However, inhibition of p38 mitogen-activated protein kinases (MAPK) abrogated 1,25(OH)2D3-induced phosphorylation and nuclear translocation of C/EBPßas well as 1,25(OH)2D3-suppressed DTC cell proliferation. Knockdown of C/EBPßreduced the expression of Notch3. Knockdown of Notch3 blocked 1,25(OH)2D3-suppressed DTC cell proliferation. In the DTC cell-derived xenograft SCID mouse, knockdown of C/EBPßmarkedly increased tumor growth and proliferation and decreased apoptosis. In DTC patients, C/EBPßwas predominantly located in the cytoplasm of DTC cells in the tumor tissue when compared with adjacent non-cancerous tissue in which C/EBPßis located in the nucleus. In conclusion, C/EBPßstimulated Notch3signaling via the p38 MAPK-dependent pathway mediates the inhibitory effect of 1,25(OH)2D on DTC cell proliferation.

Development, Reliability, and Validity of the"Knowledge-Attitude-Practice" Questionnaire of Foreigners on Traditional Chinese Medicine Treatment.

OBJECTIVE: To develop a "knowledge-attitude-practice" questionnaire as an evaluating tool of foreigners' cognition on TCM treatment, so as to promote the internationalization of TCM. METHODS: The questionnaire was based on the "knowledge-attitude-practice" model and adjusted by expert consultation using the Delphi method. After conducting a survey among foreigners, Cronbach's α and exploratory factor analysis were used to test the internal consistency reliability and structural validity of the questionnaire, respectively. RESULTS: A total of 10 experts participated in two rounds of expert consultation. The recovery rates of two rounds of expert consultation form were 100.0%. The coefficient authority in two rounds of expert consultation was 0.87 and 0.88, respectively. The concentration of expert opinions in the knowledge, attitude, and practice dimensions was 3.80 to 4.70 points, 3.70 to 4.50 points, and 3.60 to 4.40 points, respectively, in the first round and 4.30 to 4.80 points, 4.10 to 4.60 points, and 4.00 to 4.50 points, respectively, in the second round. The coefficient of variation in the knowledge, attitude, and practice dimensions was 0.10-0.32, 0.16-0.29, and 0.19-0.35, respectively, in the first round and 0.09-0.19, 0.15-0.25, and 0.16-0.31, respectively, in the second round. The W value and significance test x 2 in the first round were 0.657 and 218.620 while those in the second round were 0.671 and 181.181(P < 0.001). 8 items were deleted and 1 item was added, and other reserved items were modified according to the statistical analysis results of evaluation items and expert suggestions after the first round and there were no changes after the second round. The revised questionnaire includes three dimensions of knowledge, attitude, and practice, with a total of 30 items. After translating the questionnaire into English, it was conducted in 176 foreigners. Cronbach's α coefficient of the total questionnaire, knowledge dimension, attitude dimension, and practice dimension was 0.908, 0.781, 0.823, and 0.918, respectively. Exploratory factor analysis extracted 3 factors with a cumulative contribution of 54.090%. After testing reliability and validity, 1 item was deleted, leaving 29 items. CONCLUSIONS: After two rounds of expert consultation based on the Delphi method, the results of expert authority, expert coordination, and expert opinions' concentration were promising, and the expert consultation results were reliable. The "knowledge-attitude-practice" questionnaire of foreigners on TCM treatment in English had good reliability and validity and can evaluate foreigners' cognition on TCM treatment.

Polymorphism of ERK/PTPRR Genes in Major Depressive Disorder at Resting-State Brain Function.

The polymorphism of ERK and PTPRR in MDD is rarely reported. The present study investigated the association between the polymorphism of ERK/PTPRR and MDD at resting-state brain function using genomic imaging. It indicated that the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) in functional magnetic resonance imaging (fMRI) changed significantly in various brain regions of MDD patients. The T/G allele of ERK-rs1267842 and G/C allele of PTPRR-rs1513105 showed abnormal ALFF and ReHo changes in cortex including superior frontal gyrus and middle temporal gyrus. The development of MDD may be related with the polymorphism of ERK-rs12678428 and PTPRR-rs1513105.

Phosphoprotein Phosphatase 1 Is Required for Extracellular Calcium-Induced Keratinocyte Differentiation.

Extracellular calcium is a major regulator of keratinocyte differentiation in vitro and appears to play that role in vivo, but the mechanism is unclear. We have previously demonstrated that, following calcium stimulation, PIP5K1α is recruited by the E-cadherin-ß-catenin complex to the plasma membrane where it provides the substrate PIP2 for both PI3K and PLC-γ1. This signaling pathway is critical for calcium-induced generation of second messengers including IP3 and intracellular calcium and keratinocyte differentiation. In this study, we explored the upstream regulatory mechanism by which calcium activates PIP5K1α and the role of this activation in calcium-induced keratinocyte differentiation. We found that treatment of human keratinocytes in culture with calcium resulted in an increase in serine dephosphorylation and PIP5K1α activation. PP1 knockdown blocked extracellular calcium-induced increase in serine dephosphorylation and activity of PIP5K1α and induction of keratinocyte differentiation markers. Knockdown of PLC-γ1, the downstream effector of PIP5K1α, blocked upstream dephosphorylation and PIP5K1α activation induced by calcium. Coimmunoprecipitation revealed calcium induced recruitment of PP1 to the E-cadherin-catenin-PIP5K1α complex in the plasma membrane. These results indicate that PP1 is recruited to the extracellular calcium-dependent E-cadherin-catenin-PIP5K1α complex in the plasma membrane to activate PIP5K1α, which is required for PLC-γ1 activation leading to keratinocyte differentiation.