Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses

Complex noise with impulse or impact property is common in workplace, and its damage on the auditory system is greater than that of steady-state noise. At present, the noise exposure measurement and evaluation indicators widely used in the world mainly include the equivalent continuous sound level and the cumulative noise exposure, both are based on the equal energy hypothesis(EEH). EEH only considered the damage of noise energy on the auditory system, but ignored the effect of temporal characteristics of noise, and underestimated the degree of hearing loss associated with complex noise. This paper first introduced the limitations of current noise exposure assessment standards at home and abroad, then introduced the definition of temporal kurtosis and the calculation method of its related energy indexes(such as cumulative noise exposure and equivalent continuous A-weighted sound pressure level), and further summarized the effectiveness of temporal kurtosis as an auxiliary parameter of noise energy in assessing the risk of hearing loss caused by complex noise, providing a rationale to supplement the existing noise assessment standards.

Objective The effects of interactions between genetic and environmental factors on the noise-induced hearing loss (NIHL) are still unclear. This study aimed to assess interactions among gene polymorphisms, noise metrics, and lifestyles on the risk of NIHL. Methods A case-control study was conducted using 307 patients with NIHL and 307 matched healthy individuals from five manufacturing industries. General demographic data, lifestyle details, and noise exposure levels were recorded. The Kompetitive allele-specific polymerase chain reaction (KASP) was used to analyze the genotypes of 18 SNPs. Results GMDR model demonstrated a relevant interaction between NRN1 rs3805789 and CAT rs7943316 (P = 0.0107). Subjects with T allele of rs3805789 or T allele of rs7943316 had higher risks of NIHL than those with the SNP pair of rs3805789-CC and rs7943316-AA (P < 0.05). There was an interaction among rs3805789, rs7943316, and kurtosis (P = 0.0010). Subjects exposed to complex noise and carrying both rs3805789-CT and rs7943316-TT or rs3805789-CT/TT and rs7943316-AA had higher risks of NIHL than those exposed to steady noise and carrying both rs3805789-CC and rs7943316-AA (P < 0.05). The best six-locus model involving NRN1 rs3805789, CAT rs7943316, smoking, video volume, physical exercise, and working pressure for the risk of NIHL was found to be the interaction (P = 0.0010). An interaction was also found among smoking, video volume, physical exercise, working pressure, and kurtosis (P = 0.0107). Conclusion Concurrence of NRN1 and CAT constitutes a genetic risk factor for NIHL. Complex noise exposure significantly increases the risk of NIHL in subjects with a high genetic risk score. Interactions between genes and lifestyles as well as noise metrics and lifestyles affect the risk of NIHL.

ObjectiveTo investigate the protective effect of human urine-derived stem cells (USCs) on erectile function and cavernous structure in rats with cavernous nerve injury (CNI).

METHODSSixty adult male SD rats with normal sexual function were randomly divided into four groups of equal number: sham operation, bilateral CNI (BCNI) model control, phosphate buffered saline (PBS), and USC. The BCNI model was established in the latter three groups of rats by clamping the bilateral cavernous nerves. After modeling, the rats in the PBS and USC groups were treated by intracavernous injection of PBS at 200 μl and USCs at 1×106/200 μl PBS respectively for 28 days. Then, the maximum intracavernous pressure (mICP) and the ratio of mICP to mean arterial pressure (mICP/MAP) of the rats were calculated by electrical stimulation of the major pelvic ganglions, the proportion of nNOS- or NF200-positive nerve fibers in the total area of penile dorsal nerves determined by immunohistochemical staining, the levels of endothelial cell marker eNOS, smooth muscle marker α-SMA and collagen I detected by Western blot, and the smooth muscle to collagen ratio and the cell apoptosis rate in the corpus cavernosum measured by Masson staining and TUNEL, respectively.

RESULTSAfter 28 days of treatment, the rats in the USC group, as compared with those in the PBS and BCNI model control groups, showed significant increases in the mICP (［81 ± 9.9］ vs ［31 ± 8.3］ and ［33 ± 4.2］ mmHg, P <0.05), mICP/MAP ratio (0.72 ± 0.05 vs 0.36 ± 0.03 and 0.35 ± 0.04, P <0.05), the proportions of nNOS-positive nerve fibers (［11.31 ± 4.22］% vs ［6.86 ± 3.08］% and ［7.29 ± 4.84］% , P <0.05) and NF200-positive nerve fibers in the total area of penile dorsal nerves (［27.31 ± 3.12］% vs ［17.38 ± 2.87］% and ［19.49 ± 4.92］%, P <0.05), the eNOS/GAPDH ratio (0.52 ± 0.08 vs 0.31 ± 0.06 and 0.33 ± 0.07, P <0.05), and the α-SMA/GAPDH ratio (1.01 ± 0.09 vs 0.36 ± 0.05 and 0.38 ± 0.04, P <0.05), but a remarkable decrease in the collagen I/GAPDH ratio (0.28 ± 0.06 vs 0.68 ± 0.04 and 0.70 ± 0.10, P <0.05). The ratio of smooth muscle to collagen in the corpus cavernosum was significantly higher in the USC than in the PBS and BCNI model control groups (17.91 ± 2.86 vs 7.70 ± 3.12 and 8.21 ± 3.83, P <0.05) while the rate of cell apoptosis markedly lower in the former than in the latter two (3.31 ± 0.83 vs 9.82 ± 0.76, P <0.01; 3.31 ± 0.83 vs 9.75 ± 0.91, P <0.05).

CONCLUSIONSIntracavernous injection of USCs can protect the erectile function of the rat with cavernous nerve injury by protecting the nerves, improving the endothelial function, alleviating fibrosis and inhibiting cell apoptosis in the cavernous tissue.

Actins ; analysis ; Animals ; Arterial Pressure ; Collagen ; analysis ; Disease Models, Animal ; Erectile Dysfunction ; prevention & control ; Male ; Nitric Oxide Synthase Type I ; analysis ; Nitric Oxide Synthase Type III ; analysis ; Penile Erection ; physiology ; Penis ; innervation ; Pudendal Nerve ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Saline Solution ; administration & dosage ; Stem Cell Transplantation ; methods ; Stem Cells ; Urine ; cytology

Objective To study antioxidant role and mechanism of Rg1 in rats with cerebral ischemia reperfusion injury (IRI).Methods One hundred and twenty healthy male rats were randomly divided into six groups: control group, sham operation group, model group, different concentration (30,60,90 mg/kg) of Rg1 treatment group.MCAO SD rats model was established by suture－occluded method;the Rg1 treatment groups were given Rg1 i.p. in advance, after 24 hours of reperfusion, neurobehavioral scores of all groups were examined by Longa’s standard;The expression of Nrf2 and HO－1 were analyzed by western blot;The content of SOD and MDA was detected by kit.Results The score of model group rats are significantly higher than control group,compared with the model group, the score of different concentration of Rg1 treatment group was decreased (P＜0.05) . The Nrf2 and HO－1 expression in model group was mildly higher than the control or sham group (P＜0.05) . Both of them in every Rg1 treatment group was higher than model group. Compared with control or sham group, SOD content was observably depressed but MDA content was dramatically increased in model group,interestingly,SOD content was enhanced, MDA content was attenuated in different concentration of Rg1 treatment group (P＜0.05). Conclusion Rg1 increases Nrf2 and HO－1 protein expression and SOD content, reduces MDA content,improves neurofunctional performance of rats after MCAO,and alleviates cerebral cerebral IRI.

ObjectiveTo explore the application value of real-time contrast-enhanced ultrasound (RTCEU) in improving the detection rate of transrectal ultrasound-guided prostate biopsy.

METHODSThis prospective study included 91 male patients with abnormally high PSA (4－20 μg/L) or abnormalities in DRE or MRI, who underwent 12+X prostate biopsy following conventional transrectal ultrasonography (TRUS) and RTCEU examination. We compared the numbers of suspected prostatic nodules before and after RTCEU as well as the detection rates of prostate cancer between conventional TRUS-guided 12PBx and 12PBx plus lesion-targeted biopsy procedures.

RESULTSTotally, 57 of the 86 suspected lesions on TRUS (66.3%), and 108 of the 118 abnormal nodules on RTCEU (91.5%) were confirmed to be prostate cancer. RTCEU achieved a significantly higher detection rate than TRUS (P<0.01). A total of 39 cases of prostate cancer (42.8%) were detected by RTCEU, while only 28 (30.7%) by TRUS, with statistically significant difference in the detection rate between the two procedures (P=0.033).

CONCLUSIONSReal-time contrast-enhanced ultrasound can significantly improve the detection rate of prostate cancer and provide a valuable guide to targeted prostate biopsy.

Contrast Media ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Humans ; Magnetic Resonance Imaging ; Male ; Prospective Studies ; Prostate ; diagnostic imaging ; pathology ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; blood ; diagnostic imaging ; pathology ; Ultrasonography, Interventional

BACKGROUNDThe conventional approaches to diabetes screening are potentially limited by poor compliance and laboratory demand. This study aimed to evaluate the performance of fasting plasma glucose (FPG) and postprandial urine glucose (PUG) in screening for diabetes in Chinese high-risk population.

METHODSNine hundred and nine subjects with high-risk factors of diabetes underwent oral glucose tolerance test after an overnight fast. FPG, hemoglobin A1c, 2-h plasma glucose (2 h-PG), and 2 h-PUG were evaluated. Diabetes and prediabetes were defined by the American Diabetes Association criteria. The area under the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy of 2 h-PUG, and the optimal cut-off determined to provide the largest Youden index. Spearman correlation was used for relationship analysis.

RESULTSAmong 909 subjects, 33.4% (304/909) of subjects had prediabetes, and 17.2% (156/909) had diabetes. The 2 h-PUG was positively related to FPG and 2 h-PG (r = 0.428 and 0.551, respectively, both P < 0.001). For estimation of 2 h-PG ≥ 7.8 mmol/L and 2 h-PG ≥ 11.1 mmol/L using 2 h-PUG, the area under the ROC curve were 0.772 (95% confidence interval [CI ]: 0.738-0.806) and 0.885 (95% CI: 0.850-0.921), respectively. The corresponding optimal cut-offs for 2 h-PUG were 5.6 mmol/L and 7.5 mmol/L, respectively. Compared with FPG alone, FPG combined with 2 h-PUG had a higher sensitivity for detecting glucose abnormalities (84.1% vs. 73.7%, P < 0.001) and diabetes (82.7% vs. 48.1%, P < 0.001).

CONCLUSIONFPG combined with 2 h-PUG substantially improves the sensitivity in detecting prediabetes and diabetes relative to FPG alone, and may represent an efficient layperson-oriented diabetes screening method.

Aged ; Asian Continental Ancestry Group ; Blood Glucose ; metabolism ; Diabetes Mellitus ; blood ; diagnosis ; urine ; Fasting ; blood ; Female ; Glucose Tolerance Test ; Humans ; Male ; Mass Screening ; methods ; Middle Aged ; Postprandial Period ; physiology

Objective To explore the characteristics and their influencing factors of economic burden for pneumoconiosis disease,and to provide a baseline to develop the prevention measures and to reduce the economic burden of pneumoconiosis. Methods The retrospective epidemiological method was used to investigate the general information of pneumoconiosis cases,frequency of outpatient and hospitalization per year,medical expenditure. Direct economic loss and its influencing factors of pneumoconiosis patients were analyzed. Results A total of 421 pneumoconiosis cases were investigated. All subjects were male,including 306 inpatients. The average medical expenditures of outpatient and inpatient were 594. 53 ± 336. 23 and 32 266. 06 ± 28 130. 67 Yuan,respectively. The annual average expenditures of outpatient and inpatient were 2 907. 25 and 48 721. 75 Yuan,respectively. In terms of health care costs,the highest proportion of western medicine was 44. 08% ,followed by traditional Chinese medicine(12. 62% ). With an increase in pneumoconiosis stage,the annual frequency of outpatient and hospitalization,as well as total expenditure increased accordingly. The average annual cost of pneumoconiosis inpatient with complications and non - complication inpatient were 55 822. 20 and 23 532. 21 Yuan,respectively. The annual average cost of outpatient with complications and without complications were 4 236. 41 and 882. 31 Yuan, respectively. The expenditures for pneumoconiosis disease with complications among outpatient and inpatient were significantly higher than those of pneumoconiosis patients without complications(P < 0. 05). Conclusion Direct economic loss of pneumoconiosis disease is relatively high. The disease stage and complications of pneumoconiosis are the main factors influencing the direct economic loss of pneumoconiosis.

Objective To learn the iodine nutritional status of the vulnerable population with different iodine level under the current level of iodized salt in Shandong province and to offer prevention and cure measures.Methods Five groups of vulnerable population including school children aged 8 - 10, pregnant, lactation women, infants and women of childbearing age from mountain areas ( Daiyue, Mengyin counties ) , plain ( Luxian,Gaomi counties ) and coastal (Zhaoyuan county ) of five different iodine deficient areas were investigated in 2007.The thyroids of children aged 8 - 10 were checked by palpation and B ultrasound, their edible salt iodine level was detected by direct titration. The lever of urinary iodine of vulnerable population was examined by arsenic and cerium speetrophotometry. Results The goiter rates of 8 - 10 year-old were 1.8%(9/514) and 1.2%(6/514), respectively by palpation and B-ultrasonic. The mean iodine of 501 edible salt samples was 30.95 mg/kg. The coverage rate of iodized salt was 94.6% (474/501). The rate of qualified iodized salt was 90.4% (453/501). The median of urinary iodine was 216.7 μg,/L. The urinary iodine of school children aged 8 - 10, pregnant, lactation women, infants and women of childbearing age were 234.0, 165.5, 162.4, 257.5, 233.0 μg/L, respectively. Conclusions Current iodine nutritional level is basically appropriate in all groups of vulnerable people. The current iodine content of iodized salt could meet the needs of population from different iodine deficient areas of Shandong province.

OBJECTIVETo investigate the clinical and pathological characteristics of patients with clinically presumed hypertensive nephrosclerosis (HN).

METHODSClinical data and renal biopsy results were obtained in 63 patients diagnosed clinically as HN (primary hypertension plus renal injury).

RESULTSHN was confirmed by biopsy in 47 out of 63 patients (74.6%, 12 malignant nephrosclerosis and 35 benign nephrosclerosis). Primary nephritis (PN) was diagnosed by biopsy in 10 patients (7 IgA nephropathy, 2 mesangial proliferative nephritis, 1 chronic interstitial nephritis) and focal and segmental glomerulosclerosis (FSGS) in 6 patients. Blood pressure, body mass index, GFR and blood lipids were similar among groups. HN patients were related to higher age, more frequent family history of hypertension, longer hypertension duration, higher left ventricular mass index, lower serum creatinine and lower incidence of microscopic hematuria. Most patients with malignant nephrosclerosis and FSGS patients showed grades III and IV retinopathy.

CONCLUSIONOur results show that HN was misdiagnosed in nearly 25% patients in this cohort. Since the clinical features are similar between HN, PN and FSGS, renal biopsy is needed to establish the diagnosis of HN.

Adult ; Aged ; Female ; Humans ; Hypertension, Renal ; complications ; diagnosis ; pathology ; Kidney ; pathology ; Male ; Middle Aged ; Nephrosclerosis ; diagnosis ; etiology ; pathology