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Uromodulin, also named Tamm Horsfall protein, have been associated with renal function and sodium homeostasis regulation. The authors sought to examine the effects of salt intake on plasma and urinary uromodulin levels and the association of its genetic variants with salt sensitivity in Chinese adults. Eighty patients from our natural population cohort were maintained sequentially either on a usual diet for 3 days, a low‐salt diet (3.0 g) for 7 days, and a high‐salt diet (18.0 g) for an additional 7 days. In addition, the authors studied 514 patients of the Baoji Salt‐Sensitive Study, recruited from 124 families who received the same salt intake intervention, and investigated the association of genetic variations in uromodulin gene with salt sensitivity. Plasma uromodulin levels were significantly lower on a high‐salt diet than on a baseline diet (28.3 ± 4.5 vs. 54.9 ± 8.8 ng/ml). Daily urinary excretions of uromodulin were significantly decreased on a high‐salt diet than on a low‐salt diet (28.7 ± 6.7 vs. 157.2 ± 21.7 ng/ml). SNPs rs7193058 and rs4997081 were associated with the diastolic blood pressure (DBP), mean arterial pressure (MAP) responses to the high‐salt diet. In addition, several SNPs in the uromodulin gene were significantly associated with pulse pressure (PP) response to the low‐salt intervention. This study shows that dietary salt intake affects plasma and urinary uromodulin levels and that uromodulin may play a role in the pathophysiological process of salt sensitivity in the Chinese populations.

Background: Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be associated with risk of cardiovascular disease. We, therefore, aimed to determine the potential associations of long-term BPV from childhood to middle age with subclinical kidney damage (SKD) and albuminuria in adulthood. Methods: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, which recruited children and adolescents aged 6 to 18 years at baseline, we assessed BPV by SD and average real variability (ARV) for 30 years (6 visits). Presence of SKD was defined as estimated glomerular filtration rate between 30 and 60 mL/min per 1.73 m 2 or elevated urinary albumin-to creatinine ratio at least 30 mg/g. Albuminuria was defined as urinary albumin-to creatinine ratio ≥30 mg/g. Results: During 30 years of follow-up, of the 1771 participants, 204 SKD events occurred. After adjustment for demographic, clinical characteristics, and mean BP during 30 years, higher SD SBP , ARV SBP , SD DBP , ARV DBP , SD MAP , ARV MAP , and ARV PP were significantly associated with higher risk of SKD. When we used cumulative exposure to BP from childhood to adulthood instead of mean BP as adjustment factors, results were similar. In addition, greater long-term BPV was also associated with the risk of albuminuria. Long-term BPV from childhood to middle age was associated with higher risk of SKD and albuminuria in adulthood, independent of mean BP or cumulative exposure to BP during follow-up. Conclusions: Identifying long-term BPV from early age may assist in predicting kidney disease and cardiovascular disease in later life.

Objective Pregnancy-associated plasma protein-A2 (PAPP-A2) is the homolog of PAPP-A in the vertebrate genome and its role in protecting against salt-induced hypertension in salt-sensitive rats has been confirmed. We sought to examine the associations of plasma PAPP-A2 levels and its genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in humans. Methods Eighty participants (18-65 years old) sequentially consuming a usual diet, a 7-day low-salt diet (3.0 g/day) and a 7-day high-salt diet (18 g/day). In addition, we studied participants of the original Baoji Salt-Sensitive Study, recruited from 124 families in Northern China in 2004 who received the same salt intake intervention, and evaluated them for the development of hypertension over 14 years. Results The plasma PAPPA2 levels significantly decreased with the change from baseline to a low-salt diet and decreased further when converting from the low-salt to high-salt diet. SNP rs12042763 in the PAPP-A2 gene was significantly associated with systolic BP responses to both low-salt and high-salt diet while SNP rs2861813 showed a significant association with the changes in SBP and pulse pressure at 14-year follow-up. Additionally, SNPs rs2294654 and rs718067 demonstrated a significant association with the incidence of hypertension over the 14-year follow-up. Finally, the gene-based analysis found that Pappa2 was significantly associated with longitudinal SBP changes and the incidence of hypertension over the 14-year follow-up. Conclusions This study shows that dietary salt intake affects plasma PAPP-A2 levels and that PAPP-A2 may play a role in salt sensitivity, BP progression and development of hypertension in the Chinese populations.

Background/objectives Chronic kidney disease (CKD) is a global public health problem, including in China. The aim of this study was to identify the risk factors for the development and progression of subclinical renal disease (SRD) in a Chinese population. We also examined whether the impact of the risk factors on SRD changed over time. Subjects/methods To identify the predictors of SRD, we performed a cross-sectional study of the 2432 subjects in our Hanzhong Adolescent Hypertension Cohort. A subgroup of 202 subjects was further analyzed over a 12-year period from 2005 to 2017 to determine the risk factors for the development and progression of SRD. Results In cross-sectional analysis, elevated blood pressure, male gender, diabetes, body mass index, and triglyceride were independently associated with a higher risk of SRD. In longitudinal analysis, an increase in total cholesterol over a 4-year period and an increase in serum triglyceride over a 12-year period were independently associated with progression of albuminuria. Finally, increases in both total cholesterol and serum uric acid over a 4-year follow-up showed an independent association with a modest reduction in estimated glomerular filtration rate (eGFR). Conclusions In this study of a Chinese cohort, we show several metabolic abnormalities as independent risk factors for subclinical renal disease in a Chinese cohort. In addition, we demonstrate that the effects of total cholesterol, triglycerides and uric acid on the development and progression of albuminuria or the decline in eGFR vary at different points of follow-up. These findings highlight the importance of early detection of metabolic abnormalities to prevent SRD.

Objective Cyclooxygenase (COX)-2, an inducible isoform of the major rate-limiting enzymes that regulate the production of prostaglandins is associated with injury, inflammation and proliferation. We sought to examine whether plasma COX-2 levels and its genetic variants is associated with salt sensitivity, BP changes and/or hypertension in humans. Methods Eighty participants (aged 18-65 years) were maintained sequentially either on a usual diet for 3 days, a low-salt diet (3.0 g) for 7 days, and a high-salt diet (18.0 g) for an additional 7 days. In addition, we studied participants of the original Baoji Salt-Sensitive Study, recruited from 124 families from seven Chinese villages in 2004 who received the same salt intake intervention, and evaluated them for the development of hypertension. Results Plasma COX-2 levels were significantly decreased with reduction of salt intake from the usual to a low-salt diet and decreased further when converting from the low-salt to the high-salt diet. SNPs rs12042763 in the COX-2 gene was significantly associated with SBP responses to both low-salt and high-salt diet. SNPs rs689466 and rs12042763 were significantly associated with longitudinal changes in BPs. In addition, several COX-2 SNPs were significantly associated with incident hypertension over an 8-year follow-up. Gene-based analyses also supported the overall association of COX-2 with longitudinal changes in SBP and hypertension incidence. Conclusion This study shows that dietary salt intake affects plasma COX-2 levels and that COX-2 may play a role in salt sensitivity, BP progression and development of hypertension in the Chinese populations studied.

Corin, a transmembrane serine protease that can cleave pro-atrial natriuretic peptide (Pro-ANP) into smaller bioactive molecule atrial natriuretic peptide, has been shown to be involved in the pathophysiology of hypertension, cardiac hypertrophy. We sought to examine the associations of corin genetic variations with salt sensitivity, blood pressure (BP) changes and hypertension incidence. We studied participants of the original Baoji Salt-Sensitive cohort, recruited from 124 families from seven Chinese villages in 2004 who sequentially received a usual baseline salt diet, a 7-day low salt diet (3 g/day) and a 7-day high salt diet (18 g/day), respectively. They were followed up for 8 years (in 2009, 2012) to evaluate the development of hypertension. Corin SNP rs3749584 was significantly associated with diastolic BP (DBP) and mean arterial pressure (MAP) response to low-salt diet, while rs4695253, rs17654278 were associated with pulse pressure (PP) response to low-salt diet. SNPs rs4695253, rs12509275, rs2351783, rs2271036, rs2271037 were significantly associated with systolic BP (SBP), DBP, and MAP responses to high-salt diet. In addition, SNPs rs12641823, rs6834933, rs2271036, and rs22710367 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP over 8 years of follow-up. SNP rs73814824 was significantly associated with the incidence of hypertension over 8 years. Gene-based analysis showed that corin gene was significantly associated with longitudinal BP changes and hypertension incidence after 8-year follow-up. This study suggests that corin may play a role in salt sensitivity, BP progression, and development of hypertension.

Background. Hyperuricemia has long been associated with increased cardiovascular risk, and arterial stiffness is proposed as a mediator. The present study is aimed at examining the associations of uric acid (UA) in blood and urine with arterial stiffness in a Chinese cohort. Methods. A total of 2296 participants (mean age: 43.0 years) from our previously established cohort of Hanzhong Adolescent Hypertension Study were included. The participants were classified as subjects with or without arterial stiffness, which was defined as brachial-ankle pulse wave velocity baPWV≥1400 cm/s and/or carotid intima-media thickness CIMT≥0.9 mm. Multivariate regression analyses were used to examine the relationship between serum and urinary UA and the risk of arterial stiffness after adjusting for age, gender, systolic blood pressure, fasting glucose, BMI, heart rate, total cholesterol, and triglycerides. Results. baPWV was positively correlated with urinary uric acid/creatinine ratio (uUA/Cre) (β=0.061, P<0.001), while CIMT was correlated with uUA/Cre (β=0.085, P<0.001) and fractional excretion of uric acid (FEUA) (β=0.044, P=0.033) in all subjects. In addition, uUA/Cre was significantly associated with the risk of high baPWV [1.032 (1.019-1.045)] and arterial stiffness [1.028 (1.016-1.040)]. Conclusion. Our study showed that urinary UA excretion was significantly associated with the risk of arterial stiffness in Chinese adults. These findings suggest that UA, especially urinary UA, may be used as a simple, noninvasive marker for early detection of arterial stiffness in otherwise healthy subjects.

Objective Atherosclerotic diseases are the leading cause of death worldwide. This study aimed to investigate the predictors of brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (CIMT) progression in a Chinese cohort over a 12-year follow-up period and to determine whether these predictors differ by follow-up time. Methods A total of 202 participants were recruited from a previously established cohort in Shaanxi Province, China. Both baPWV and CIMT were measured in 2013 and 2017. Multivariable regression was used to determine the predictors of CIMT and baPWV progression. Results Men had higher CIMT and baPWV and a higher rate of CIMT progression during two follow-ups than women. A 4-year change in SBP was associated with baPWV progression, whereas a 12-year change in DBP was associated with baPWV progression. The increased progression of baPWV presented a linear trend when subgrouping all the participants according to SBP and DBP changes over 4 and 12 years, respectively. In addition, heart rate (HR) change over 4 and 12 years was consistently associated with CIMT progression, and a linear trend was also seen when subgrouping the population. Conclusion Our study demonstrated that SBP and DBP contributed differently in different stages to the progression of arterial stiffness in this Chinese cohort. Moreover, HR was consistently involved in the increased progression of CIMT in all periods. These findings underline the importance of early detection and control of blood pressure and resting HR for the prevention of arterial stiffness progression.

Background/Aims: The aim of our study was to investigate the effect of high-salt diet on the renal expression of renalase and the potential role of the local renin-angiotensin system in this process. Methods: Sprague-Dawley (SD) rats were divided into groups according to salt content in diet and drug treatment as follows: normal-salt diet (NS), high-salt diet (HS), high-salt intake with hydralazine (HS+H), high-salt diet with enalapril (HS+E), and high-salt diet with valsartan (HS+V). The dietary intervention and drugs were given for four weeks. Renin activity and angiotensin II type 1 receptor (AT1R) levels were detected by real-time PCR. Renalase mRNA and protein were also measured. Results: After four weeks, systolic blood pressure and proteinuria were significantly increased in the HS group with respect to the NS group. Dietary salt intake caused a dramatic decrease in renalase expression in the rat kidneys. Renal cortex renin and AT1R increased significantly in the HS and HS+H groups. Urinary protein was positively correlated with renal renin and AT1R levels. However, in the HS+E and HS+V groups, enalapril and valsartan failed to influence renal renalase expression but abolished the increase in proteinuria, renal cortex renin, and AT1R levels with respect to the HS group. Conclusion: This study indicates that high salt intake reduces renal expression, and renal RAS may be not involved in the regulation of renalase in SD rats fed with high-salt diet.

Ultra Wideband (UWB) technology is promising for wireless personal area network (WPAN) applications due to its high data rate, low power requirement and short-range characteristics. Instead of exploring new unused frequency band, the UWB communication follows the overlay principle, i.e., sharing the spectrum with existing systems and devices. This novel radio technology has been recently approved by the regulatory authorities in the United States and Canada, and is being considered for approval in Europe and Asia. In this paper, an overview of the UWB radio technology from the technical, economical, and regulatory perspectives is provided. Firstly, the definition of UWB by the Federal Communications Commission (FCC) is introduced, followed by a brief introduction to the history. The current status of the standardization process resulting from the FCC’s recent decision to permit unlicensed operation in the [3.1–10.6] GHz band is discussed. Then, the reasons of considering UWB as a future solution for WLAN/WPAN applications are studied. In particular, the unique properties of UWB and its difference from other wireless technology alternatives are studied. Then, the benefits and challenges related to the commercial deployment of UWB for future applications are discussed. Finally, the research problems and challenges posed by the UWB technology are focused.

To outline the clinical manifestations and compare the different radiological methods of detecting malformation of cervical segment of internal carotid artery.A retrospective analysis of 7 cases with malformation of cervical segment of internal carotid artery between May, 2004 and April, 2011. CT angiography (CTA) and magnetic resonance angiography (MRA) were used to detect the morphology of cervical segment of internal carotid artery.This disease entity provided no obvious symptoms in five cases, and such complains as pharyngeal foreign body sensation in one and odynophagia in another. Physical examination showed a bulge with pulsation on pharyngeal wall in four cases, and apparent normal pharynges in other three patients, all of which were covered with intact pharyngeal mucosa. Twelve carotid arteries were observed in seven cases, five of which were showed tortuosity and seven kinking. All of the five patients with recorded radiological materials had identified malformations of internal carotid artery, two of which were tortuosity bilaterally and two kinking bilaterally and one tortuosity and kinking respectively. CTA and MRA revealed tortuosity of cervical segment of internal carotid arteries.No typical clinical symptoms were shown in the malformation of cervical segment of internal carotid artery. Pharyngeal bulge with pulsation could be encountered. CTA and MRA showed excellent ability to depict the malformation of cervical segment of internal carotid artery and its relationship with surrounding structures, which could protect carotid artery from unintended damage.

To establish a simple, rapid, inexpensive and sensitive method for detecting hot region for mutations in exon 7 of PAH gene.High-resolution melting (HRM) technology was used to detect a c.728GA mutation in exon 7 in 88 patients with classical type phenylketonuria. Suspected mutations were validated by direct DNA sequencing.The results detected by HRM are in good agreement with the results obtained by direct sequencing.HRM analysis is a simple, rapid, inexpensive and sensitive method for detecting hot mutational region in exon 7 of PAH gene.

The variation in mutations in exons 3, 6, 7, 11 and 12 of the phenylalanine hydroxylase (PAH) gene was investigated in 59 children with phenylketonuria (PKU) and 100 normal children. Three single nucleotide polymorphisms were detected by sequence analysis. The mutational frequencies of cDNA 696, cDNA 735 and cDNA 1155 in patients were 96.2%, 76.1% and 7.6%, respectively, whereas in healthy children the corresponding frequencies were 97.0%, 77.3% and 8.3%. In addition, 81 mutations accounted for 61.0% of the mutant alleles. R111X, H64 > TfsX9 and S70 del accounted for 5.1%, 0.8% and 0.8% mutation of alleles in exon 3, whereas EX6-96A > G accounted for 10.2% mutation of alleles in exon 6. R243Q had the highest incidence in exon 7 (12.7%), followed by Ivs7 + 2 T > A (5.1%) and T278I (2.5%). G247V, R252Q, L255S, R261Q and E280K accounted for 0.8% while Y356X and V399V accounted for 5.9% and 5.1%, respectively, in exon 11. R413P and A434D accounted for 5.9% and 2.5%, respectively, in exon 12. Seventy-two variant alleles accounted for the 16 mutations observed here. The mutation characteristics and distributions demonstrated that EX6-96A > G and R243Q were the hot regions for mutations in the PAH gene in Shanxi patients with PKU.

To study the mutations in exons 3, 6, 7, 11 and 12 of the phenylalanine hydroxylase gene (PAH) in Shanxi population.The mutations in exons 3, 6, 7, 11 and 12 and flanking sequences of PAH gene were detected by PCR-DNA sequencing, in 59 patients with phynelketonuria(PKU) and 100 healthy children from Shanxi province.By sequence analysis, three single nucleotide polymorphism (SNP) Q232Q (CAACAG), V245V (GTGGTA) and L385L (CTGCTC) were detected in both the patients and healthy children, with the frequencies of nt 696, 735 and 1155 of the PAH cDNA up to 96.2%, 76.1% and 7.6% in patients respectively, and 97.0%, 77.3% and 8.3% respectively in the healthy controls. In addition, 72 different mutations accounting for 61.0% of mutant alleles were identified in the patients only. In exon 3, R111X, H64TfsX9 and S70 del were found accounting for 5.1%, 0.8% and 0.8%; EX6-96AG in exon 6 was found accounting for 10.2%. In exon 7, R243Q was the highest incidence accounting for 12.7%, followed by Ivs7+2 TA(5.1%) and T278I(2.5%); the lowest incidences were G247V, R252Q, L255S, R261Q and E280K accounting for 0.8 %, respectively. In exon 11, Y356X (5.9%) and V399V (5.1%) were found; in exon 12, R413P and A434D were found accounting for 5.9% and 2.5%. In total, 9 missense mutations, 3 splice site mutations, 2 nonsense mutations and 2 deletions were included in 16 kinds of different mutations.The mutation characteristics and distribution in exons 3, 6, 7, 11 and 12 of the PAH gene have been identified, and it suggested that the EX6-96AG and R243Q were the hot spots of PAH gene mutations in Shanxi PKU population.

Laminoplasty has become a common alternative to laminectomy for cervical spondylotic myelopathy or radiculopathy. The procedures have been compared before, but data on functional recovery are limited. We aim to compare the safety and short-term clinical and functional outcomes of cervical laminoplasty and cervical laminectomy.We performed a retrospective analysis of the outcome of 72 patients who had laminoplasty and 49 patients who had laminectomy at our hospital from 1999 to 2005. Patients had cervical spondylotic myelopathy or radiculopathy. All of the patients were similar in age and pre-operative functional status. All patients were assessed pre-operatively and 4 months post-operatively with the Rankin disability score, Glasgow outcome scale and Karnofsky and Nurick scales.Laminoplasty resulted in greater improvement than laminectomy on the Rankin scale (p0.0001, chi-square test), GOS (p0.0027, chi-square test) and Karnofsky scores (p0.01, Wilcoxon test). Nurick scores improved in both groups without a significant difference (p0.62, Wilcoxon test). The proportion of patients who improved on all scales tended to be greater in the laminoplasty group. Patients spent 1.8 fewer days in the hospital after laminoplasty (p=0.04, Wilcoxon rank-sum test). There was no mortality or permanent morbidity for either procedure.Both cervical laminectomy and laminoplasty are safe and effective for the treatment of cervical myelopathy or radiculopathy. Cervical laminoplasty results in a shorter hospital stay and greater functional improvement at 4 months follow-up.

To compare the clinical benefits of rapid Rhino Stammberger sinus dressing (RR), a new nasal packing material for functional endoscopic sinus surgery (ESS), with traditional packing materials sorbalgon plus Vaseline gauze (SV) prospectively.Twenty-four patients with chronic sinusitis of the similar grade were enrolled in the study. After ESS, the nasal cavities of each patient were packed with RR in the right side as observing group and SV in the left side as control group. SV in the left nasal cavity was removed in the first day after operation and RR remained in the right nasal cavity until the first endoscopic follow-up 1 week postoperatively. The same perioperative treatments such as irrigation and local steroid were given in both sides of nasal cavities. The grade of rhinalgia, nasal obstruction, discharge, bleeding and epiphora in each side of nasal cavities were assessed on a visual analogue scale (VAS) by the patients at the operation day (packing period), the first day and the second day after operation respectively. Postoperative endoscopic assessment of nasal cavities including crust, discharge, pseudomembrane, edema of mucosa, bubble and ostium obstruction were carried out by a rhinologist on VAS at 1, 2, 3, 4, 6, 8 weeks postoperatively. The follow-up continued until the complete mucosal healing.Three patients were dropped from statistical analysis. One of them with severe hypertension bleeding when he awoke from anesthesia, the RR was run out from the nasal cavity. The other two were lost in the follow-up. Twenty-one patients completed the follow -up ranging between 2-20 months. The scores of rhinalgia, epiphora at the operation day and the rhinalgia at the first day after operation in RR side were lower than SV side (P0.05). The scores of the amount of crust at the first week after operation in RR side were lower than SV side (P0.05). Statistically, no significant deference was found between RR and SV in the length of mucosal healing period.Patients felt more comfortable with the package of RR than traditional material. No pain and secondary bleeding happened. The efficacy of RR on mucosal healing was similar with SV. RR showed some advantages and could be used as packing material following ESS.

To study the relation between hereditary nonsyndromic hearing impairment (NSHI) in Chinese and mutation in Connexin 31 (Cx31) gene and to explore the pathogenic mechanism.Forty-seven pedigrees with hereditary NSHI, 38 Children with sporadic NSHI and cases of control were collected in present studies. The coding sequence of Cx31 gene was amplified by polymerase chain reaction (PCR), screened by denaturing high-performance liquid chromatography (DHPLC) and confirmed by direct sequencing.The mutation rate of heterozygous mutation C --T at position 798 of Cx31 cDNA in patient group and in control were 14.1% (12/85) and 1% (1/100) respectively. Significant difference was found between the two group (P0.01). Heterozygous mutation G --A at position 580 of GJB3 cDNA, which results in a missense mutation (A194T), was found in two members of one pedigree with autosomal dominant NSHI. The mutation was not found in numbers with normal hearing of this pedigree and controls. Heterozygous mutation G --A at position 250 of Cx31 cDNA was found in one child with sporadic congenital NSHI. In our previous studies, Cx26 gene mutations have been screened among the patient with hereditary NSHI and sporadic NSHI and the control of our test, and two Cx26 gene mutations were found in two pedigrees. But the two NSHI pedigrees which were confirmed to have Cx26 gene mutation were not found to have Cx31 mutation. The patient and the control which were confirmed to have Cx31 gene mutations were not found to have Cx26 mutations.Cx31 gene was associated with nonsyndromic hearing impairment There was no cross and cooperative effect between Cx26 gene and Cx31 gene.

To study the use of spiral computed tomography three-dimensional images (SCT-3DI) in the evaluation of patients with laryngotracheal stenosis. The value and utility of SCT-3DI compared with actual endoscopy were also investigated in terms of accuracy of diagnosis and validity of treatment.Eight patients with laryngotracheal stenosis were underwent SCT-3DI and regular endoscopy examination preoperatively. Of eight patients, Five had traumatic causes, two with tracheal narrowing due to tracheal granulomas, one with too much scar tissue of unknown etiology in the subglottic area. The location, extent and contour of the stenosis were identified and compared with actual endoscopy findings, and confirmed by surgical procedures.SCT-3DI evaluation was accurate in assessing the length, width and shape of all the laryngotracheal stenosis in our study. The results of SCT-3DI were best correlated with actual endoscopy findings and those found in the surgery. Based on the SCT-3DI, five patients were treated by open surgical techniques including laryngotracheal reconstruction procedures and dilation methods with hyoid grafts or stents. Two undertaken endoscopic treatment with CO2 laser excision of scar tissue or granulomas, one accepted no surgical procedures. All eight patients were successfully decannulated with improved voice and satisfied airway after 6-month postoperative follow-up.Evaluation of the upper airway with SCT-3DI is useful in the diagnosis, measurement, and definition of the laryngotracheal stenosis. Objective data obtained from SCT-3DI is very helpful for operative scheme. Patients treated with appropriate procedures best suited for every stenosis have reached satisfactory clinical results.