OBJECTIVE: To learn the influence the gentamycin on C57BL/6J mice hear and cochlear hair cell ribbon synapses CaV1.3 calcium protein amount. To explore the relationship between hear loss and its dosage correlation change and significance. METHOD: The fixed amino glucoside to C57BL/6J mice was used to make abdominal cavity injection mold every day. The auditory brain-stem response ABR was used to measure the hear of mice in 7th, 14th, 28th after the injection. Immunofluorescence method was used to observe cochlear basement membrane of hair ribbon synapse CaV1.3 calcium channel proteins in the distribution and expression. Inner hair cells synaptic membrane was immune fluorescent tags with CtbP2 and CaV1. 3. RESULT: With the growth of the injected drugs, ABR threshold increased,but all the hair cells and shape had no obvious change. However the amount of hair rib bon synapse CaV1.3 calcium ion channel proteins in the expression had significant differences (P < 0.01). CaV1.3 calcium ion channel proteins increased slightly lower than normal at 7th day, significantly decreased at 14th day, had increased, increased quantity compare with 14th day, but at 28th day after intraperitoneal injection of gentamicin. CONCLUSION The increasing,decreasing and increasing trend of cochlear hair cells CaV1.3 proteins in the environment of amino glucoside drug toxicity showed that the increase of hair ribbon synapse CaV1.3 proteins may have a compensatory effect on the drug toxicity. With the increase of the drug toxicity effect, this kind of decompensated function could be the listening decline, which may be one of the mechanism of damage to hearing.
Animals ; Calcium Channels, L-Type ; metabolism ; Evoked Potentials, Auditory, Brain Stem ; Gentamicins ; pharmacology ; Hair Cells, Auditory, Inner ; drug effects ; metabolism ; Mice ; Mice, Inbred C57BL ; Proteomics

Objective To systematically evaluate the influence of acupuncture-moxibustion on the peroneal nerve conduction velocity in type 2 diabetic peripheral neuropathy (DPN), and to provide clinical references for acupuncture-moxibustion treatment for DPN.Method By searching the CBM, CNKI, VIP, Wanfang, Pubmed, Springer and Medline databases, randomized controlled trials (RCT) of acupuncture-moxibustion for the type 2 DPN published from January 2000 to January 2014 were retrieved and the relevant data of the peroneal nerve conduction velocity were collected for methodological evaluation. RevMan 5.1 software was adopted to conduct the meta-analysis.Result Totally 10 RCTs were recruited with 685 cases involved, including 355 cases in the treatment group and 330 cases in the control group. The meta-analysis results indicated that acupuncture-moxibustion can produce a better effect in improving the motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of peroneal nerve in type 2 DPN than the treatments used in the control group, and the differences were statistically significant between the two groups [MD=3.55, 95%CI (0.79, 6.31); MD=4.10, 95%CI (0.22, 7.99)].Conclusion Acupuncture-moxibustion can improve the peroneal nerve conduction velocity in type 2 DPN, and thus is worth application in clinic. Due to the limitation of the included studies, such as small sample size and low quality of the articles and high probability of bias, RCTs of large sample size and high quality are required to confirm the above conclusions.

Objective To study the diagnosis and treatment of Mycobacterium avium complex lung disease with severe renal insufficiency,and to provide a basis for improving the clinical diagnosis and treatment of MAC lung disease with severe renal insufficiency.Methods Clinical data of an elderly patient with MAC lung disease confirmed by induced sputum culture and complicated with chronic kidney disease (CKD 4) was reported.The related literatures at home and abroad were reviewed.Results A male patient aged 80 years with poor nutrition was suffering from progressive weight loss,exhaustion and night sweats.His weight was only 43-44 Kg.Chest CT showed that multiple small nodules,small spot pieces of shadow and ground glass shadows in bilateral lung tissues.PET/CT indicated that spot pieces and nodules with metabolic activity in high performance.Bronchoalveolar lavage fluid (BALF) inspection was negative.MAC was identified by induced sputum culture through high permeability brine induced sputum.It was difficult to choose drugs for the treatment of MAC lung disease due to his poor kidney function [GFR of left kidney:9.0 ml /min,GFR of right kidney:18.8 ml/min].Conventional anti-mycobacterium drugs showed a low to high resistance to MAC.Moxifloxacin was discontinued for renal insufficiency.His condition was stable after choosing trimodality therapy including azithromycin 0.25 g/d tiw,rifapentine 0.3 g/d biw,ethambutol 0.375 g /d tiw and the joining immunotherapy.Conclusions PET/ CT is not useful in identifying tuberculosis and MAC lung disease.The treatment of MAC lung disease is difficult in elderly patients with severe renal insufficiency and low weight.Individual therapy combined with immunotherapy and improving the nutrition state is a good choice for the treatment of MAC lung disease in elderly patients with severe renal insufficiency.The anti-MAC drugs should be carefully selected and the adverse reactions should be closely observed in order to obtain the satisfactory clinical results.

Objective:To provide microsurgical anatomy data in the course, branch, distribution, arterial network profile of the submental artery and the range of the flap excision in submental flap transplantation.Methods:From March, 2015 to March, 2020, a total of 36 head and neck cast specimens were studied. Acrylic-butadience-styrene plastic (ABS) filler were perfused into the external carotid artery to make cast specimens. The course, branching, distribution and the arterial framework of the submental artery under a surgical microscope were investigated.Results:The submental artery originated from the facial artery before reaching the lower edge of the mandible (1.50±0.50) cm, with a diameter of (1.50±0.85) (0.6-2.3) mm. The main trunk of submental artery was (5.5±0.5) cm in length, which ran forward along the lower edge of the mandible and branched out (9.0±3.0) (7-13) branches with diameters between 0.1-0.5 mm, and mainly distributed to skin and superficial fascia of the submental area. The main trunk of submental artery divided into ascending, horizontal and descending branches about 3.0 cm of the midline of the mandible. The ascending branch went upwards over the lower edge of the mandible and joined up with the lower labial arch or participated in the formation of the lower labial arch; the horizontal branch divided into several branches and joined up with the branches from the opposite side; the descending branch branched posteriorly and inferiorly, joined up with branches of lingual artery and superior thyroid artery. The branches of the submental artery and the branches of the peripheral arteries were joined up in the submental area to form the submental artery network. The diameter of the vessels in the network ranged 0.1-0.2 mm. The arterial network was built in the form of 1 to 3 layers, and the area of main network was about 7.0 cm×5.0 cm.Conclusion:The submental artery has a long trunk, many branches and abundant anastomoses between the branches, forming a dense submental artery network, which provides sufficient pedicle length, rich blood supply and cutting area for submental flap. The flap can be transplanted free or transposed. The best location of submental flap is near the midline of arterial network, and the appropriate area is 7.0 cm×5.0 cm.

To report the clinical, imaging, and pathological feature of a rare case of central precocious puberty with primary pigmented nodular adrenocortical disease(PPNAD), and to conduct a retrospective analysis of PPNAD with relevant literatures. The pubic hair was found in the child for more than one year. Physical examination showed Cushing′s syndrome. ACTH in blood decreased, cortisol rhythm was disordered, 24-hour urine free cortisol increased and the paradoxical increase of urine free cortisol after high dose dexamethasone suppression test. Adrenal enhancement computed tomography(CT)showed multiple small nodular shadows in bilateral adrenal glands. Gonadotropin releasing hormone(GnRH)stimulation test supported central precocious puberty and GnRH analogue was used to control the sexual development. PPNAD was supported by pathology result. The symptoms of Cushing′s syndrome were relieved partially after left adrenalectomy.

OBJECTIVETo early assess the impaired renal function in the obese children with non-alcoholic fatty liver disease (NAFLD) and to identify the relationship between NAFLD and impairment of renal function.

METHODSThree hundred and eighty-six obese children were enrolled and divided into NAFLD group and simple obesity group (control) according to the diagnostic criteria. Clinical biochemical parameters and early impaired renal functions were evaluated and compared. Among all patients 234 obese children aged over 10 y were subdivided into 3 groups: NAFLD combined with metabolic syndrome (NAFLD+MS) group, NAFLD group and simple obesity group (control), and the above indexes were compared among 3 groups.

RESULTSThe urinary microalbumin levels in NAFLD, NAFLD+MS (>10y) and NAFLD groups (>10y) were significantly higher than those in controls. Additionally, the positive correlations of urinary microalbumin with systolic pressure, triglyceride and 2h-postprandial blood glucose were found.

CONCLUSIONThere is early renal dysfunction in children with NAFLD and those accompanied with MS, which may be associated with hypertension and glucose-lipid metabolic disorder. The results indicate that NAFLD is not only an early sign of early impaired renal function but also an early stage of chronic kidney disease (CKD) in obese children.

Adolescent ; Albuminuria ; diagnosis ; Child ; Child, Preschool ; Fatty Liver ; complications ; physiopathology ; Female ; Humans ; Kidney ; physiopathology ; Male ; Non-alcoholic Fatty Liver Disease ; Obesity ; complications ; physiopathology

OBJECTIVETo compare and evaluate clinical applications of two definitions of metabolic syndrome in children and adolescents, which was developed by Pediatric Academy of Chinese Medical Association in 2012 (Chinese definition) and by International Diabetes Federation in 2007 (IDF definition), respectively.

METHODS593 obese children and adolescents aged 10 ≊16 y from July 2006 to December 2012 were enrolled in the study. The diagnostic concordance of two definitions for metabolic syndrome and individual components was estimated, and their sensitivity and specificity for detecting insulin resistance and early macrovascular complications were compared.

RESULTSThe concordance between two definitions for diagnosing metabolic syndrome was good (kappa=0.626); as for detecting the individual components, the Kappa concordance index were 1.000, 0.803, 0.780, 0.734 and 0.594 for hypertriglyceridemia, hyperglycemia, cholesterol abnormality and hypertension, respectively. The incidence of insulin resistance and early macrovascular complications, detected by the two definitions, were both increased with increasing number of abnormal components. The sensitivity and specificity for detecting insulin resistance in children with metabolic syndrome were 54.5% and 65.7% by Chinese definition, and 36.1% and 83.1% by IDF definition; while the sensitivity and specificity for detecting early macrovascular complications were 58.3% and 55.8% by Chinese definition, and 37.3% and 70.8% by IDF definition. After adjusting for age and sex, compared to the obese children and adolescents without metabolic syndrome, the odds ratios of insulin resistance and early macrovascular complications were 2.166 (P<0.001) and 1.771(P=0.008) for children with metabolic syndrome diagnosed by Chinese definition, and the odds ratio of insulin resistance and early macrovascular complications were 2.618 (P<0.001) and 1.357 (P=0.190) by IDF definition.

CONCLUSIONThe concordance between Chinese and IDF definitions for diagnosing metabolic syndrome in Chinese obese children and adolescents is good. Compared to IDF definition, Chinese definition is more sensitive for hypertension, hyperglycemia and hypercholesterolemia, thus it can more effectively detect insulin resistance and early macrovascular complication.

Adolescent ; Child ; Female ; Humans ; Insulin Resistance ; Male ; Metabolic Syndrome ; classification ; complications ; diagnosis ; Obesity ; complications ; Sensitivity and Specificity

PURPOSE: The present study was designed to determine whether rapamycin could inhibit transforming growth factor beta1 (TGF-beta1)-induced fibrogenesis in primary lung fibroblasts, and whether the effect of inhibition would occur through the mammalian target of rapamycin (mTOR) and its downstream p70S6K pathway. MATERIALS AND METHODS: Primary normal human lung fibroblasts were obtained from histological normal lung tissue of 3 patients with primary spontaneous pneumothorax. Growth arrested, synchronized fibroblasts were treated with TGF-beta1 (10 ng/mL) and different concentrations of rapamycin (0.01, 0.1, 1, 10 ng/mL) for 24 h. We assessed m-TOR, p-mTOR, S6K1, p-S6K1 by Western blot analysis, detected type III collagen and fibronectin secreting by ELISA assay, and determined type III collagen and fibronectin mRNA levels by real-time PCR assay. RESULTS: Rapamycin significantly reduced TGF-beta1-induced type III collagen and fibronectin levels, as well as type III collagen and fibronectin mRNA levels. Furthermore, we also found that TGF-beta1-induced mTOR and p70S6K phosphorylation were significantly down-regulated by rapamycin. The mTOR/p70S6K pathway was activated through the TGF-beta1-mediated fibrogenic response in primary human lung fibroblasts. CONCLUSION: These results indicate that rapamycin effectively suppresses TGF-beta1-induced type III collagen and fibronectin levels in primary human lung fibroblasts partly through the mTOR/p70S6K pathway. Rapamycin has a potential value in the treatment of pulmonary fibrosis.
Cells, Cultured ; Collagen Type III/metabolism ; Fibroblasts/*drug effects/metabolism/physiology ; Fibronectins/metabolism ; Humans ; Lung/cytology/drug effects ; Pulmonary Fibrosis/drug therapy ; Signal Transduction/drug effects ; Sirolimus/*pharmacology ; TOR Serine-Threonine Kinases/metabolism/physiology ; Transforming Growth Factor beta1/*antagonists & inhibitors/physiology

Objective To design and synthesize novel triazole antifungal derivatives with 1 ,3 ,4-oxadiazole side chain for the study of antifungal activities. Methods Fourteen title compounds were synthesized via acylation ,aminolysis reaction ,cy-clization ,nucleophilic substitution ,etc. All the compounds were characterized by 1 H NMR ,MS spectra. The in vitro antifun-gal activities were evaluated against six human pathogenic fungi through the micro-broth dilution method. Results The title compounds exhibited strong antifungal activities against all the tested fungi ,especially against Candida albicans. Compounds 10d ,10i , 10l , and 10n were found to be the most effective , with a minimum inhibitory concentration (MIC80 ) of 0.003 9 μg/ml .They are 16-fold more potent than ICZ ( MIC80 0.062 5 μg/ml) and 64-fold more potent than FCZ (MIC80 0.25 μg/ml) .Conclusion The 1 ,3 ,4-oxadiazole side chain could affect the antifungal activities. That could be due to the prop-er incorporation between the 1 ,3 ,4-oxadiazole substituted phenyl ring with the target enzyme.

Abdominal aortic aneurysm (AAA) is a life-threatening disorder worldwide. Fibroblast growth factor 21 (FGF21) was shown to display a high level in the plasma of patients with AAA; however, its detailed functions underlying AAA pathogenesis are unclear. An in vitro AAA model was established in human aortic vascular smooth muscle cells (HASMCs) by angiotensin II (Ang-II) stimulation. Cell counting kit-8, wound healing, and Transwell assays were utilized for measuring cell proliferation and migration. RT-qPCR was used for detecting mRNA expression of FGF21 and activating transcription factor 4 (ATF4). Western blotting was utilized for assessing protein levels of FGF21, ATF4, and markers for the contractile phenotype of HASMCs. ChIP and luciferase reporter assays were implemented for identifying the binding relation between AFT4 and FGF21 promoters. FGF21 and ATF4 were both upregulated in Ang-II-treated HASMCs. Knocking down FGF21 attenuated Ang-IIinduced proliferation, migration, and phenotype switch of HASMCs. ATF4 activated FGF21 transcription by binding to its promoter. FGF21 overexpression reversed AFT4 silencing-mediated inhibition of cell proliferation, migration, and phenotype switch.ATF4 transcriptionally upregulates FGF21 to promote the proliferation, migration, and phenotype switch of Ang-II-treated HASMCs.