Objective To investigate the endothelial dysfunction in pre-hypertension and its influencing factors.Methods A total of 373 youth were divided as the subjects into hypertension group (HBP group),prehypertension group (PHT group) and normal blood pressure group (NBP group).Endothelial function was assessed based on carotid intima-media thickness (IMT),brachial artery flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV).Results IMT and baPWV in PHT group were higher than those in NBP group (P＜0.05),but did not reach the significant difference when compared with HBP group (P＞0.05).Compared with HBP,the levels of FMD in PHT group significantly increased (P＜ 0.05);however,no difference was observed in comparison with NBP group (P＞0.05).In the early stage of hypertension,diastolic BP (β=-0.120,P＜0.05) and body mass index (β=-0.115,P＜0.05) were negatively correlated with FMD;diastolic BP (β=0.146,P＜0.05),2-hour glucose (β=0.147,P＜0.05),high-density lipoprotein cholestrol (β=0.150,P＜0.05),and waist-hip ratio (β=0.126,P＜0.05) showed a positive correlation with IMT.baPWV was correlated with systolicBP (β=0.358,P＜0.01),waist circumference (β=0.254,P＜0.05),fasting glucose (β=0.155,P＜0.05),postprandial 2 h blood glucose (β =0.152,P ＜0.05),uric acid (β =0.206,P ＜ 0.05),and C-reactive protein (β=0.099,P＜0.05).Corclusion Our study shows that endothelial dysfunction may exist in the prehypertensive young,and several cardiovascular risks contribute to its development in the early stage of hypertension.

Objective To investigate the effect and potential mechanism of autophagy inhibitor chloroquine on the calcium oxalate crystals formation in rats.Methods From September 2016 to October 2016,Thirty healthy male SD rats were randomly divided into 3 groups:control group,model group and chloroquine intervention group.The method to establish calcium oxalate stone model was drinking water with 1％ ethylene and 1％ ammonium chloride freely.The rats of chloroquine intervention group were treat with chloroquine (40mg/kg · d) by intraperitoneal injection.Modeling was finished after 28 days.The amounts of renalcalcium oxalate crystals were detected by polarizing microscope.For all groups,the amounts of autophagosome were detected by transmission electron microscope.Twenty four hour urine compositions for stone risk factors were detected.The expressions of oxidative stress injury related molecular markers (SOD,MCP-1 and 8-OHdG) and the expressions of autophagy markers (LC3 and P62) were detected by immunohistochemistry.The RNA expressions of SLC26A6 in kidney were detected by Real-time PCR.Results Compared to the model group,the amounts of renal calcium oxalate crystals were significantly reduced in chloroquine intervention group (32.37 ± 5.14 vs.4.18 ± 0.25,P ＜ 0.05).Compared to the control group,the level of autophagy was increased in the model group.Compared to the model group,the level of autophagy was inhibited in the chloroquine intervention group.For control group,model group and chloroquine intervention group,the excretion of urinary oxalate were (3.1 ± 1.5) mmol,(22.5 ± 8.1) mmol,(2.8 ± 1.2) mmol,respectively;the excretion of urinary citrate were (63.4 ± 7.4) mmol,(45.9 ± 9.5)mmol,(15.6 ± 8.2) mmol,respectively.Compared to the control group,the amounts of urinary oxalate weresignificantly elevated in model group (P ＜ 0.05),but citrate were significantly reduced in the chloroquineintervention group(P ＜ 0.05).For control group,model group and chloroquine intervention group,theexpressions of SOD were 42.24 ±4.16,19.21 ± 2.25,39.08 3.53,respectively;the expressions of MCP-1 were 4.02 0.51,8.45 ± 0.55,5.52 ± 0.34,respectively;the expressions of 8-OHdG were 7.16 ± 0.54,11.21 ± 1.12,8.67 ±0.34,respectively;the RNA expressions of SLC26A6 were 0.35 ±0.07,1.02 ±0.17,0.70 ± 0.06,respectively.Compared to the control group,the expressions of SOD were significantly reduced in the model group,but the expressions of MCP-1,8-OHdG and SLC26A6 were significantly elevated(P ＜0.05).Compared to the model group,the expressions of SOD were significantly elevated chloroquine intervention group (P ＜ 0.05),but the expressions of MCP-1,8-OHdG and SLC26A6 were significantly elevated(P ＜ 0.05).Conclusions The autophagy inhibitor chloroquine could inhibit the formation of calcium oxalate crystals induced by ethylene in rat kidney via inhibit the renal autophagy level and expressions of the SLC26A6,reducing the renal oxidative stress injury and urinary oxalate excretion.

Objective To explore the differences between patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) accompanied with or without community-acquired pneumonia (CAP).Methods We collected 141 patients with COPD who met the admission criteria and had multiple acute exacerbation hospitalization history.Among them,40 patients with AECOPD accompanied with or without acute exacerbation of hospitalization of CAP (group A),38 patients with AECOPD accompanied with acute exacerbation of hospitalization of CAP (group B) and 63 patients with AECOPD but without acute exacerbation of hospitalization of CAP (group C).The demographic differences of age,sex and smoking status were analyzed and compared.The clinical symptoms and blood-related inflammatory indicators of pa tients in group A were analyzed and compared under the acute aggravation of CAP.The number of acute hospitalizations in 12 months before onset and 12 months after discharge were tracked.Results The age,smoking rate,COPD-GOLD classification,dyspnea index,anxiety and depression score in group A were higher than those in group B and C,while the percentage of forced expiratory volume in the first second (FEV1) in predicted value was lower than that in group B and C.The proportion of patients who cooperated or needed long-term home oxygen therapy and drug therapy was higher than that in group B and C,with statistical significance (P ＜ 0.05),but there was no statistical difference in each index between group B and C (P ＞ 0.05).The clinical symptoms of cough,expectoration,fever and other blood-related inflammatory indicators were aggravated in group A when accompanied with CAP.The number of acute hospitalizations in 12 months after discharge of AECOPD without CAP was significantly higher than that of COPD with CAP (P ＜ 0.05),while there was no significant difference in blood gas analysis indicators between the two cases (P ＞ 0.05).The number of hospitalizations in 12 months after discharge,percentage of neutrophils (N)and the level of interleukin (IL)-17 were independent clinical predictors of COPD with CAP.Conclusions Patients with AECOPD accompanied with or without CAP (group A) had poor lung function,worse illness conditions,greater support of home oxygen therapy and drug therapy and poor quality of life.Patients with AECOPD accompanied with CAP had more symptoms and higher levels of inflammatory indicators,but less risk of re-hospitalization in 12 months after cure than AECOPD patients without CAP.The number of hospitalization in 12 month after discharge,the percentage of neutrophils (N),and IL-17 level were helpful in screening the patients with CAP from the AECOPD patients.

Essential palatal tremor is relatively rare in clinical practice, which manifests involuntary and rhythmic contraction of soft-palate along with auditory click. The cause is unknown and there is no specific treatment at present. This article reports a female patient with essential palatine tremor, who presented with involuntarily beating of soft palate, disappeared during sleep, had sensory tricks, and gradually developed mental and psychological problems such as anxiety disorders. After treatment with integrated traditional Chinese and Western medicine, the symptoms improved. The clinical features of the case were analyzed, relevant literature was reviewed, and the possible etiology and characteristics of the disease were explored, so as to provide reference for clinical diagnosis and treatment.

OBJECTIVE: To explore the genetic basis for 4 patients with globozoospermia. METHODS: Semen and blood samples were collected from the patients for the determination of sperm concentration, viability, survival rate, morphology and acrosome antigen CD46. Meanwhile, DNA was extracted for whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing. RESULTS: All of the four patients were found to harbor variants of the DPY19L2 gene. Patients 1 ~ 3 had homozygous deletions of the DPY19L2 gene. Sanger sequencing confirmed that the DPY19L2 gene in patient 3 was disrupted at a recombination breakpoint area BP2, resulting in nonallelic homologous recombination and complete deletion of the DPY19L2 gene. Patients 2 and 3 respectively harbored novel homozygous deletions of exons 2 ~ 22 and exons 14 ~ 15. Patient 4 harbored heterozygous deletion of the DPY19L2 gene, in addition with a rare homozygous deletion of the 3' UTR region. CONCLUSION DPY19L2 gene variants probably underlay the globozoospermia in the four patients, which has fit an autosomal recessive pattern of inheritance and the characteristics of genomic diseases.
Male ; Humans ; Teratozoospermia/genetics* ; Homozygote ; Semen ; Sequence Deletion ; 3' Untranslated Regions ; Membrane Proteins

Objective To observe whether the IL-23/Th17 inflammatory pathway is involved in the development of calcific aortic valve disease,and whether secukinumab can delay the progression of calcific aortic valve disease by inhibiting this pathway.Methods Forty-seven mice were divided into a blank control group,model group,and secukinumab group according to the random number table method.The blank control group was fed normal chow,while the model group and secukinumab group were fed pro-calcification chow for 16 weeks to establish a calcific aortic valve disease model.After intervention with secukinumab for 4 weeks,peak flow velocity changes in the aortic valves were detected under Doppler ultrasonography in all mice.Relevant indexes were determined by hematoxylin and eosin staining,Von Kossa staining,immunohistochemical staining,ELISA,and qPCR.Results Compared with the model group,the secukinumab group showed significantly reduced peak flow velocity(P＜0.05)and serum IL-6,IL-17,and IL-23 levels(P＜0.05)in the aortic valve.Compared with the secukinumab group,the model group's leaflet thickness was significantly increased,and there were more calcium deposits.Immunohistochemical result showed that macrophage infiltration(P＜0.05),IL-17A(P＜0.05)and IL-23(P＞0.05)levels in the valve leaflets were reduced in the secukinumab group compared with the model group.PCR result suggested that the expression of STAT3,BMP-2,and α-SMA mRNA was significantly lower in the secukinumab group than the model group(P＜0.05).Conclusions The IL-23/Th17 inflammatory pathway is involved in the pathogenesis of calcific aortic valve disease.The inflammation,fibrosis,osteogenic differentiation,and calcification of mouse valves were alleviated after intervention with secukinumab,which may delay disease progression by inhibiting the IL-23/Th17 inflammatory pathway.

Objective To investigate the ameliorative effects and potential mechanism of Lithocarpus litseifoliu on renal function and inflammation in mice with hyperuricemic nephropathy(HN).Methods The HN model was established by the combined administration of adenine and potassium oxyzate.The mice were randomly divided into normal control group,model control group,benzbromarone group,and high,medium and low dose groups of Lithocarpus litseifoliu.Different drugs were given to the mice,and their body mass was recorded once a week.The levels of uric acid(UA),creatinine(Cr),urine protein(UP),blood urea nitrogen(BUN)and urine urea nitrogen(UUN)as well as the levels of tumor necrosis factor α(TNF-α)and interleukin 6(IL-6)in serum or urine of each group were collected and measured on the 21st day.Hematoxylin-eosin(HE)staining was performed to observe kidney tissue injury in mice;real-time PCR(RT-PCR)was performed to determine ATP-binding cassette subfamily G member 2(ABCG2),urate transporter protein(URAT1),glucose transporter protein 9(GLUT9),and cytosolic factor NF-κB p50(κB p50)in kidney tissues.Results Compared with the normal control group,the body mass of mice in the model control group was significantly lower after the second weeks of modeling(P＜0.05),and the levels of UA,Cr,UP,BUN,UUN,TNF-α,IL-6 contents and GLUT9 mRNA and κB p50 mRNA expression contents of kidney tissues were significantly higher(P＜0.01,P＜0.05).Compared with the model control group,the levels of Cr,UP,BUN and UUN contents and renal tissue nuclear cytokine κB p50 mRNA expression were significantly lower in the high,medium and low dose groups of Lithocarpus litseifoliu(P＜0.01,P＜0.05).The UA levels were significantly lower in the high dose group of Lithocarpus litseifoliu(P＜0.05),and renal ABCG2 mRNA expression was significantly higher in the medium dose group(P＜0.01).The renal URAT1 mRNA expression was significantly decreased in the low dose group(P＜0.01).Conclusion Lithocarpus litseifoliu has shown ameliorative effects on HN mice,and the mechanism may be related to the modulation of renal uric acid transporters,improvement of renal function and anti-inflammation effects.

Marinesco-Sj?gren syndrome (MSS), also known as hereditary ataxia-dwarf-mental retardation syndrome, is a rare autosomal recessive ataxia syndrome. This article reviews the recent advance in clinic characteristics, pathogenic gene mutation sites, pathogenesis and clinic diagnosis and treatment of MSS, in order to improve clinicians' understanding of the disease and diagnosis and treatment level, and reduce the missed diagnosis and misdiagnosis of the disease.

Sialidosis is a rare lysosomal storage disease caused by NEU1 gene mutation at 6p21.33. It is characterized by myoclonic, ataxia, epilepsy, and decreased vision. A pair of twins with sialidosis type 1 are reported to enrich clinicians ′ understanding of the disease, so as to improve the diagnosis and treatment. The proband was a 16-year-old male. The main symptom was intermittent limb involuntary trembling for 2 years, with paroxysmal loss of consciousness. Fundus examination showed cherry-red spots. His twin brother had similar symptoms, but the overall performance was mild. Whole exome sequencing results showed that both patients carried compound heterozygous mutations of c.239C>T (p.P80L) and c.803A>G (p.Y268C) in NEU1 gene, which were from their normal phenotype mother and father.

Objective:To improve the dosimetric accuracy of cell irradiation experiments by developing a method of accurately measuring the absorbed dose of ultra-thin solution in culture dishes under 200 kV medium-energy X-rays using EBT3 films.Methods:EBT3 film dose calibration was performed under Cyberknife 6 MV beam, and the beam quality (half-value layer) and effective energy of the 200 kV beam used in this study generated from Small Animal Radiation Research Platform through measurements and calculations were obtained to determine the EBT3 energy response correction factor. The 200 kV beam was utilized to irradiate three commonly used culture dishes filled with ultra-thin liquid placed on EBT3 films and the corrected EBT3 doses were taken as the liquid absorbed doses. The dose linearity of immersed films was also measured and analyzed. In addition, after modeling the irradiation environment, the independent Monte Carlo calculations of the liquid absorbed dose were performed by MCNP5 program. The calculation results were compared with the film measurement results to verify the accuracy of the measured doses.Results:The 200 kV beam had a half-value layer of 8.77 mm aluminum and effective energy of 57.4 keV, corresponding to an energy response correction factor of 0.889. The average liquid absorbed doses of large, medium and small culture dishes measured by EBT3 films under the specified parameters of 200 kV beam were (1.434±0.004) Gy, (1.467±0.011) Gy and (1.469±0.027) Gy after correction, respectively. The percentage errors from the corresponding Monte Carlo calculation doses were 0.07%, -0.70%, and 0.47%, respectively, where the relatively consistent results could be found. In addition, the dose linearity of immersed EBT3 films was also good, with coefficient of determination R2=0.9972. Conclusion:The method of measuring the dose of ultra-thin cell solution using EBT3 films proposed in this study is feasible, and the dose results obtained yield high accuracy under 200 kV beam.