Objective This study was designed to explore the effect of hyperglycemia on the expression of Toll-like receptor 4 (TLR4 ) in renal tubular epithelial cells and its significance in diabetic nephropathy. Methods In vitro cultured renal tubular epithelial cells ( NRK-52E) were divided into LG group (cultured in 5mmol / L glucose DMEM) and HC group (cultured in 25mmol / L glucose DMEM). Cells were harvested at different time points. Immunohistochemistry, Rt-PCR, Western Blot were used to detect TLR4 protein and mRNA expression, and the levels of IL-6 and TNF-α from the cell culture supernatant were determined by EL1SA assay. Results After 6 hours, there was increased expression TLR4 mRNA in HC group, which appeared to be maintained for 24 hours and began to decrease after 48 hours ( P < 0.05). TLR4 protein expression increased in HC group after 24 hours, and increased even further after 48 hours. Compared with LG groups, the difference had statistical significance ( P <0.05). In HG group, IL-6 and TNF-α expression in the supernatant from the NRK-52E culture were significantly increased ( P < 0.05) , and the expression of IL-6 and TNF-α was positive correlated with the expression of TLR4 protein ( r =0.799,0.820). Conclusion High glucose triggers an increase in expression of TLR4 in NRK-52E cells, itself leading to an increase in expression of inflammatory factors such as TNF-α and IL-6. In this way, TLR4 participates in the progress of diabetic nephropathy.

Objective To determine the effect of aldosterone and its antagonist, spironolactone on epithelial-mesenchymal transition (EMT) of normal rat kidney epithelial cells (NRK-52E) in a high glucose milieu,and to explore the mechanism of renoprotection in diabetic nephropathy (DN ) in rats involving aldosterone and spironolacton. Methods NRK-52E cells were simultaneously cultured in the serum-free Dulbecco's modification of Eagle's medium Dulbecco (DMEM) for 12 hours. Then the low glucose (LG) group was cultured in LG (1000 mg/L) DMEM:The high glucose (HG) group was cultured in high glucose (4 500 mg/L) DMEM. The aldosterone (Aldo) groups were cultured in high glucose DMEM with the addition of 10,50 and 100 nmol/L aldosterone respectively. The SP group was cultured in high glucose (4 500 mg/L) DMEM plus 10~(-7)mol/L spironolactone. Immunohistochemistry, RT-PCR and Western blot were used to detect E-cadherin and α smooth muscle actin(α-SMA) mRNA expression. Results RT-PCR showed that compared with the LG Group, E-cadherin mRNA expression in the HG group was significantly lower, and α-SMA mRNA expression was significantly increased(P＜0.05). E-cadherin mRNA expression in the 50 nmol/L Aldo group and 100 nmol/L Aldo group was significantly lower than that in the HG group, while the expression of α-SMA mRNA was significantly increased in the HG group(P＜0.05), with a dose-dependent relationship with aldosterone(r=-0.70,P＜0.05;r=0.67, P＜0.05). E-cadherin mRNA in the SP group was significantly higher,while α-SMA mRNA expression was lower than that in the HG group(P＜0.01). Immunohistochemistry and Western blot showed that compared with the LG group, E-cadherin protein expression was significantly reduced, and α-SMA expression was significantly increased in the HG group(P＜0.01). In the 10 nmol/L Aldo, 50 nmol/L Aldo, and the 100 nmol/L Aldo groups, E-cadherin protein expression was significantly lower, and α-SMA protein expression was significantly higher than that in the HG group(P＜0.05), with a dose-dependent relationship with aldosterone(r=-0.83,P＜0.05;r=0.81, P＜0.05). In the SP group, E-cadherin protein expression was higher, and α-SMA protein level was lower than that in the HG group(P＜0.05). Conclusion Aldosterone can promote EMT of tubular epithelial cells in a high sugar milieu, leading to renal interstitial fibrosis in Diabetic nephropathy. Spironolactone can inhibit high glucose-induced renal tubular epithelial cells EMT, which may be an important mechanism for the inhibition of renal interstitial fibrosis.

Objective To explore the association between fibroblast growth factor 23 (FGF-23) and calcium (Ca)-phosphorus(P) metabolism and bone mineral density (BMD) in patients on peritoneal dialysis.Methods Fifty-nine patients undergoing continuous ambulatory peritoneal dialysis(CAPD) were enrolled in this study.These patients were divided into three groups as normal, osteopenic and osteoporotic, according to World Health Organization criteria based on bone mineral density T scores.Another 30 healthy people were also enrolled as control group.Levels of serum FGF-23 and 1,25 (OH)2VitD3 were measured by ELISA.Parathyroid horomone(PTH) was detected by immunoradiometric assay.Calcium and phosphorus were assessed with autobiochemistry machine.Bone density was studied by dual-energy X-ray absorptiometry (DEXA).Results The incidences of osteoporosis at the femur neck and lumbar spine in CAPD patients were 23.7％ and 35.6％, respectively.Among three groups of CADP patients, no significant differences were found in the levels of serum FGF-23, while the level of serum FGF-23 in CAPD group was higher than that in control gronp(P＜0.01).A positive correlation was found between log [FGF-23]and serum phosphorus(r=0.604, P＜0.01).However, a negative correlation was found between log[FGF-23]and 1,25(OH)2VitD3 and GFR (r=-0.401, P＜0.05; r=-0.651, P＜0.01).There were no correlations of log [FGF-23]with PTH, Ca, T scores and the duration of dialysis.Conclusions In CAPD patients, serum FGF-23 increases significantly.Serum phosphorus, renal function and 1,25(OH)2VitD3may play an important role in adjusting the level of serum FGF-23, while FGF-23 has no direct effect on bone mineralization in CAPD patients.

Objective To assess the efficiency and safety of mycophenolate mofetil (MMF) in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO). Methods Twenty-seven patients with MS or NMO were selected, and the patients were divided into 2 groups:MMF group (MMF combined with glucocorticoid treatment group, 10 cases) and glucocorticoid group (only glucocorticoid treatment group, 17 cases). There were 5 cases with MS and 5 cases with NMO in MMF group. There were 13 cases with MS and 4 cases with NMO in glucocorticoid group. The therapeutic efficacy 6 months after treatment, expanded disability status scale (EDSS) before treatment and 6 months after treatment, and annualized relapse rate (ARR) were compared; and the safety was observed. Results There was no statistical difference in efficacy rate 6 months after treatment between MMF group and glucocorticoid group: 9/10 vs. 11/17, P>0.05. The EDSS scores 6 months after treatment in MMF group and glucocorticoid group were significantly lower than those before treatment: (2.41 ± 2.05) scores vs. (3.40 ± 2.05) scores and (1.17 ± 0.92) scores vs. (2.38 ± 1.28) scores, and there were statistical differences (P<0.05), particularly for the patients with MS. The ARR 6 months after treatment in MMF group was significantly lower than that before treatment: 0 time/year vs. 0.75 times/year, and there was statistical difference (P<0.05). The difference of ARR before and after treatment in MMF group was significantly higher than that in glucocorticoid group: 0.75 times/year vs.- 0.46 times/year, and there was statistical difference (P<0.01), particularly for the patients with MS. Only 1 female patient had myalgia when taking higher dosage of MMF, and the symptom tended to relieve after the dosage was reduced. Conclusions MMF is effective in the treatment of MS and NMO. MS can improve the neurological function and reduce the recurrence of the disease;and the safety is high.

Female ; Humans ; Hyperkalemia ; therapy ; Infant, Newborn ; Male ; Peritoneal Dialysis ; instrumentation

In order to find the optimal topographical factor for regionslization, the content of cimetidine in 116 Sinopodophyllum hexandrum sample collected from Sichuan, Qinghai, Gansu, Tibet, Yunnan and Shaanxi provinces, was determined. Using mathematical statistics and geographical spatial analysis of GIS analysis, the relationship between content of podophyllotoxin and influencing factors including altitude gradient and gradient position was analyzed. It is found that the optimal altitude was 2 800 m to 3 600 m, the aspect of slope north or northeast and northwest and the slope 12 degrees to 65 degrees with a high suitability degree. Considering the artificial planting, the suitable planting area for S. hexandrum is comfirmed. The topographical factor is important for S. hexandrum regionalization, but has hardly effect on podophyllotoxin content. The results of the study provide an important scientific basis for S. hexandrum production development. But there are many factors which affect suitability index and podophyllotoxin content of S. hexandrum, it is necessary to consider other factors like climate and soil while exploitation and protection of S. hexandrum.
Altitude ; Berberidaceae ; chemistry ; growth & development ; China ; Ecosystem ; Podophyllotoxin ; analysis

Aged ; Alcoholic Beverages ; Humans ; Hyponatremia ; etiology ; Male ; Substance Withdrawal Syndrome ; complications

Objective To investigate the effect of electroacupuncture on diaphragm function of chronic obstructive pulmonary disease (COPD) rats with muscular dystrophy, and to explore the regulatory mechanism. Methods Forty male rats were randomly divided into blank group, model group, electroacupuncture group, exercise group, electroacupuncture plus exercise group, 8 rats in each group. After successful establishment of COPD rat model with muscular dystrophy, the modeled rats in various intervention groups were given electroacupuncture and/or exercise treatment. After the last treatment, the changes of rat body mass were observed, the rat lung function was detected, and the mRNA expression levels of myosin heavy chains (MHC) of MHC-1, MHC-2 and diaphragmatic related signal proteins of Atrogin-1, muscle ring-finger protein-1(MuRF-1), MyoD were detected by real-time quantitative polymerase chain reaction (qPCR). Results (1) Compared with the blank group, inspiratory resistance (IR) and functional residual mass (FRC) in the model group were increased (P < 0.05) , and the dynamic lung compliance(Cydn) was decreased(P<0.05). Compared with the model group, IR and FRC in the intervention groups were decreased (P < 0.05), but the differences among the three intervention groups were insignificant(P>0.05). (2) Compared with the blank group, the mRNA expression levels of MHC-1, Atrogin-1, MuRF-1, MyoD in the model group were increased (P<0.05), and the mRNA expression level of MHC-2 was decreased (P < 0.05). Compared with the model group, the mRNA expression levels of MHC-1, Atrogin-1, MuRF-1, MyoD in the intervention groups were decreased (P < 0.05) , and the mRNA expression level of MHC-2 was increased(P<0.05). Compared with the exercise group, the mRNA expression levels of Atrogin-1, MuRF-1, MyoD in the electroacupuncture group were decreased (P<0.05), and the mRNA expression level of MHC-2 was increased (P<0.05) , but the above indexes in electroacupuncture plus exercise group showed no obvious changes(P>0.05). Conclusion Electroacupuncture can improve respiratory function of COPD rats with muscular dystrophy, and the possible mechanism is related with the increase of MHC-2 mRNA expression and with the decrease of Atrogin-1, MuRF-1, MyoD mRNA expression, which result into the regulation of ubiquitin proteasome pathway(UPP), reduction of myosin loss, and the relief of diaphragmatic atrophy.

Mild traumatic brain injury (mTBI) is a common type of brain disorders among young adults. The dysfunction of the brain is often exacerbated due to diffuse axonal injury (DAI) which based on the injury of white matter fibers and axons. Since mild and moderate brain injury or DAI are diffuse and subtle, conventional CT and MRI are difficult to make a positive diagnosis. Recent clinical study indicated that functional magnetic resonance imaging has a high detection rate in the diagnosis of acute mild and moderate brain injury, especially the diffusion tensor imaging (DTI) and 1H-magnetic resonance spectroscopy (1H-MRS). This paper has reviewed the principles and characteristics of DTI and 1H-MRS, and recent research in the clinical and animal experiments on brain injury.
Animals ; Axons/pathology* ; Brain/pathology* ; Brain Concussion/pathology* ; Brain Injuries/pathology* ; Diagnosis, Differential ; Diffuse Axonal Injury/pathology* ; Diffusion Tensor Imaging ; Humans ; Magnetic Resonance Spectroscopy/methods* ; Nerve Fibers, Myelinated/pathology* ; Severity of Illness Index

Objective: Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying N-acetyl-α-neuraminidase-1 (NEU1) variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1. Methods: First, whole-exome sequencing and detailed clinical examinations were performed on the family. Second, structural analyses, including assessments of energy, flexibility and polar contacts, were conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed. Results: We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by a sialidase activity assay. Cherry-red spots were more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal electroencephalographies and visual evoked potentials had a relatively early age of onset, whereas patients with myoclonus had a late onset. Conclusion Changes in flexibility and local polar contacts may be indicators of NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.