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Circular RNAs (circRNAs) play an important regulatory role in human diseases, including diabetic nephropathy (DN). The purpose of this study was to investigate the role and mechanism of circHOMER1 action in DN.Human mesangial cells (HMCs) were tested with high glucose (HG) to mimic DN cell models. Quantitative real-time PCR was performed to determine circHOMER1, microRNA (miR)-137 and SRY-box transcription factor 6 (SOX6) expression. SOD activity and MDA level were detected to evaluate cell oxidative stress. ELISA assay was used to analyse the levels of inflammation factors. The protein levels of extracellular matrix (ECM) deposition-related markers and SOX6 were assessed by western blot analysis. The interaction between miR-137 and circHOMER1 or SOX6 was analysed by dual-luciferase reporter assay and RNA pull-down assay.CircHOMER1 was highly expressed in HG-induced HMCs and DN patients. Downregulation of circHOMER1 suppressed oxidative stress, inflammation and ECM deposition in HMCs induced by HG. In terms of mechanism, circHOMER1 could sponge miR-137 to regulate SOX6. Function assays showed that miR-137 inhibitor or SOX6 overexpression revoked the negative regulation of circHOMER1 knockdown on HG-induced HMCs injury. In addition, miR-137 expression was negatively correlated with circHOMER1 and SOX6 expression in DN patients.CircHOMER1 promoted HG-induced HMCs oxidative stress, inflammation and ECM accumulation via the miR-137/SOX6 axis, suggesting that circHOMER1 might be a target for DN treatment.

Accumulation and concomitant risk of metals in plastic-shed soil (PSS)-vegetable system around industrial areas have attracted growing public concern recently, while limited studies have focused on human bioaccessible metals in various plastic-shed vegetables and health risk calculated using bioaccessible metals. Previous studies showed that intensive farming and industrial activities could prominently affect metal migration from PSS to vegetables via altering PSS pH, total and bioavailable metal contents. In contrast, whether changes in PSS pH and metal contents control bioaccessible metals in vegetables and health risk is still unknown. For PSS management and sustainable plastic-shed vegetable production in the areas with rapid industrialization, 41 PSS and 32 plastic-shed vegetable samples were sampled from the industrial areas of Yangtze River Delta, China to systematically clarify the specific connections among anthropogenic activities, soil pH and metal contents, and metal transfer and health risk in PSS-vegetable-human system. The results indicated that Cr and Cd contents in 15.6% and 9.38% of vegetable samples exceeded the allowable limits in China. Tolerable cancer risk existed and was mainly induced by bioaccessible Cr in vegetables. Decreased PSS pH mainly caused by heavy use of nitrogen fertilizers increased bioavailable Ni, Cd, Zn, Pb, and Cu in PSS and subsequently enhanced their total and bioaccessible contents in vegetables. Prominent Cr accumulation in PSS induced by industrial wastewater irrigation exacerbated Cr uptake by vegetables, which increased bioaccessible Cr in vegetables and contributed greatly to cancer risk. To reduce transfer and health risk especially of Cd and Cr in the food chain, some appropriate measures related to source control and remediation should be proposed for preventing and mitigating PSS acidification and Cr accumulation.

Diabetes mellitus (DM) is a group of metabolic disorders in which high blood sugar levels occur over a prolonged period. Approximately 4% of the global population is affected by DM. Western medical treatment methods for diabetes including injection or oral hypoglycemic drugs have some toxic or side effects, economic pressures, and so on. Many researchers turn to discover new drugs from natural products or Traditional Chinese Medicine (TCM). Flavonoids are widely distributed in plants, and many studies have shown that flavonoids possess antidiabetic properties, exhibiting not only well-recognized antidiabetic and hypoglycemic activities but also activity in the treatment of diabetic complications. In this review, we systematically summarized anti-diabetic flavonoid compounds based on structure classification by examining the PubMed, Springer Link, Web of Science, and CNKI databases. There are 13 flavonoid compounds listed which have been studied extensively and have antidiabetic features respectively. Apigenin, baicalein, and catechin mainly reduces blood glucose via anti-oxidation; hesperidin is good for diabetic neuropathy; glycyrrhiza flavonoids have a significant effect on gestational DM; quercetin takes advantage of crossing the blood–brain barrier and improving renal function. Some compounds have protective and preventive effects on diabetic complications, such as kaempferol and puerarin which are beneficial to cardiomyopathy; myricetin has therapeutic potential in the treatment of DN; dihydromyricetin might improve CI. It is a pity or might be a pointcut that most studies remain in the animal experimental stage, and further investigation should be carried out.

Background Recent studies have identified susceptibility genes of HBV clearance, chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, and showed the host genetic factors play an important role in these HBV-related outcomes. Methods Collected samples from different outcomes of HBV infection and performed genotyping by Affymetrix 500 k SNP Array. GCTA tool, PLINK, and Bonferroni method were applied for analysis of genotyping and disease progression. ANOVA was used to evaluate the significance of the association between biomarkers and genotypes in healthy controls. PoMo, FST, Vcftools and Rehh package were used for building the racial tree and population analysis. FST statistics accesses 0.15 was used as a threshold to detect the signature of selection. Results There are 1031 participants passed quality control from 1104 participants, including 275 HBV clearance, 92 asymptomatic persistence infection (ASPI), 93 chronic hepatitis B (CHB), 188 HBV-related decompensated cirrhosis (DC), 214 HBV-related hepatocellular carcinoma (HCC) and 169 healthy controls (HC). In the case–control study, one novel locus significantly associated with CHB (SNP: rs1264473, Gene: GRHL2, P = 1.57 × 10−6) and HCC (SNP: rs2833856, Gene: EVA1C, P = 1.62 × 10−6; SNP: rs4661093, Gene: ETV3, P = 2.26 × 10−6). In the trend study across progressive stages post HBV infection, one novel locus (SNP: rs1537862, Gene: LACE1, P = 1.85 × 10−6), and three MHC loci (HLA-DRB1, HLA-DPB1, HLA-DPA2) showed significant increased progressive risk from ASPI to CHB. Underlying the evolutionary study of HBV-related genes in public database, the derived allele of two HBV clearance related loci, rs3077 and rs9277542, are under strong selection in European population. Conclusions In this study, we identified several novel candidate genes associated with individual HBV infectious outcomes, progressive stages, and liver enzymes. Two SNPs that show selective significance (HLA-DPA1, HLA-DPB1) in non-East Asian (European, American, South Asian) versus East Asian, indicating that host genetic factors contribute to the ethnic disparities of susceptibility of HBV infection. Taken together, these findings provided a new insight into the role of host genetic factors in HBV related outcomes and progression.

The Keap1-Nrf2/ARE signaling pathway is an important defense system against exogenous and endogenous oxidative stress injury. The dysregulation of the signaling pathway is associated with many diseases, such as cancer, diabetes, and respiratory diseases. Over the years, a wide range of natural products has provided sufficient resources for the discovery of potential therapeutic drugs. Among them, polyphenols possess Nrf2 activation, not only inhibit the production of ROS, inhibit Keap1-Nrf2 protein-protein interaction, but also degrade Keap1 and regulate the Nrf2 related pathway. In fact, with the continuous improvement of natural polyphenols separation and purification technology and further studies on the Keap1-Nrf2 molecular mechanism, more and more natural polyphenols monomer components of Nrf2 activators have been gradually discovered. In this view, we summarize the research status of natural polyphenols that have been found with apparent Nrf2 activation and their action modes. On the whole, this review may guide the design of novel Keap1-Nrf2 activator.

The occurrence and development of tumors are closely related to epigenetic instability which modulates gene expression through DNA methylation, histone modification, chromatin remodeling, and RNA-related silencing. Histone deacetylase (HDAC) and poly (ADP-ribose) polymerase (PARP) are targets of epigenetic regulation. Over the years, a large number of studies have shown that HDAC inhibitors and PARP inhibitors have synergistic effects in the treatment of tumors, and there are reports of related dual HDAC/PARP inhibitors. This review will give a brief summary of the synergistic mechanisms of HDAC inhibitors and PARP inhibitors and introduce the design of the first dual HDAC/PARP inhibitor, which may guide the design of more dual HDAC/PARP inhibitors for the treatment of tumors.

ObjectiveTo investigate the prevalence of thyroid dysfunction (TD) and IgG subclasses of thyroid autoantibodies (TAs) and to determine the predictive factors of TD in chronic hepatitis C (CHC) patients.DesignThree hundred and twelve untreated hepatitis C virus-infected patients without a history of TD or treatment with thyroid hormones were enrolled in a cross-sectional study. Clinical and biological factors were statistically analyzed to determine the correlation between TD and this patient population.ResultsThe incidence of TD was 12.5% in CHC patients. Clinical hypothyroidism (5.8%) and subclinical hypothyroidism (3.8%) were more frequent than clinical hyperthyroidism (1.6%) and subclinical hyperthyroidism (1.3%). The percentage of TA-positive patients was significantly higher in people >60 years than in those ≤60 years (31.9 vs 18.6%; P=0.042). Positive thyroid peroxidase antibody (TPOAb) was more frequent, and alanine aminotransferase (ALT) levels were lower in patients who displayed TD (TPOAb: 62.1 vs 10.8%, P=0.000; ALT: 43.5 vs 51 IU/l, P=0.046). The positive percentage of TPOAb IgG2 subclass in the TD group was significantly higher than that of patients without TD (66.7 vs 16.7%, P=0.005). Multiple logistic regression analysis indicated that only TPOAb IgG2 subclass positivity was an independent risk factor for TD in CHC patients (odds ratio=8; 95% CI: 1.225–52.246; P=0.030).ConclusionsTPOAb IgG2 subclass positivity is a risk factor for TD in CHC patients before antiviral treatment. IgG2 subclass of TPOAb might play an important role in the presence of TD in CHC patients.

Objective To develop a patient safety culture instrument for use in Chinese hospitals, we assessed the appropriateness of existing safety culture questionnaires used in the USA and Japan for Chinese respondents and identified new items and domains suitable to Chinese hospitals. Design Focus group study. Setting and participants Twenty-four physicians, nurses and other health-care workers from 11 hospitals in three Chinese cities. Methods Three focus groups were conducted in 2010 to elicit information from hospital workers about their perceptions of the appropriateness and importance of each of 97 questionnaire items, derived from a literature review and an expert panel, characterizing hospital safety culture. Results Participants understood the concepts of patient safety and safety culture and identified features associated with safe care. They judged that numerous questions from existing surveys were inappropriate, including 39 items that were dropped because they were judged unimportant, semantically redundant, confusing, ambiguous or inapplicable in Chinese settings. Participants endorsed eight new items and three additional dimensions addressing staff training, mentoring of new hires, compliance with rules and procedures, equipment availability and leadership walk-rounds they judged appropriate to assessing safety culture in Chinese hospitals. This process resulted in a 66-item instrument for testing in cognitive interviews, the next stage of survey development. Conclusions Focus group participants provided important insights into the refinement of existing items and the construction of new items for measuring patient safety culture in Chinese hospitals. This is a necessary first step in producing a culturally appropriate instrument applicable to specific local contexts.

To study the mechanism underlying the effect of the SOCS3 rs4969170 A/G alleles on the occurrence of insulin resistance (IR) in patients with chronic hepatitis C.The promoter region of the SOCS3 gene was amplified by PCR,and luciferase expression vectors were constructed and transfected into HepG2,Huh7 cell lines.The relative luciferase activity of each expression vector was assessed by the dual luciferase reporter gene assay system.Western blotting was used to detect SOCS3 protein expression in PBMCs from groups of patients with the rs4969170 AA and AG genotypes.The state of IR in eight patients was evaluated by determining their HOMA-IR.The pGL3-A, PGL3-G and pGL3-control vectors showed significantly different luciferase expression in the HepG2 cells (0.121 00 ± 0.022 07,0.027 00+/-0.012 49 and 0.043 33 ± 0.005 51; F =48.068, P=0.001) and in the Huh7 cell lines (0.164 70 ± 0.007 10,0.027 33 ± 0.017 04 and 0.033 67 ± 0.014 98; F =115.137, P=0.001). The expression of SOCS3 protein was significantly higher in the rs4969170 AA genotype group than in the AG genotype group (1.22 ± 0.40 vs. 0.30 ± 0.19; t =4.149, P=0.006).The IR index of patients with the rs4969170 AA genotype and the AG genotype was 4.11 ± 2.62 and 1.47 ± 1.01 respectively.There were three patients with IR in the rs4969170 AA genotype group and one in the rs4969170 AG group. There was no statistically significant difference between the two genotype groups (t=1.881, P=0.109).The SOCS3 rs4969170 A haplotype may enhance transcriptional activity of the gene promoter to regulate gene expression, thereby increasing intracellular SOCS3 protein level and ultimately interfering with insulin signaling and causing IR in patients with chronic hepatitis C.

To investigate the effect of salvianolic acid B (SA-B) on renal interstitial fibrosis due to unilateral ureteral obstruction.Thirty-six SD male rats were randomly divided into 3 groups, 12 in each group, the sham-operated group, the model group and the SA-B treated group. The rat model of renal interstitial fibrosis was successfully established by unilateral ureteral obstruction (UUO). Rats in the SA-B treated group was intragastrically administrated with SA-B (12.5 mg x kg(-1)) daily after modeling. Rats of each group were killed respectively at day 14 and day 21 after UUO. Pathological changes of renal tissue were observed by hematoxylin and eosin (HE) staining. The expression of alpha-smooth muscle actin (alpha-SMA) in kidney was determined with immunohistochemistry. And the expressions of cytokeratinl9 (ck19) mRNA in renal tissue were detected using reverse transcription polymerase chain reaction (RT-PCR).Renal interstitial fibrosis was obviously ameliorate in SA-B treated group. The expression of alpha-SMA was significantly decreased in SA-B treated group as compared with that in model group at day 14. And the expression of ck19 was significantly lower than that determined in model group at day 21.SA-B could ameliorate renal interstial fibrosis due to UUO, probable by inhibiting epithelial-to-myofibroblast transdifferentiation and the activation of myofibroblast.

To primarily investigate the changing mode of anti-SARS coronavirus IgG antibody in clinically diagnosed SARS patients and the possibility of subclinical infection in physicians and nurses through close association with SARS patients.The plasma levels of anti-SARS coronavirus IgG antibody of 57 normal subjects, 127 physicians and nurses worked in SARS wards for one month and 73 SARS patients with different course of SARS were measured by enzyme linked immunosorbent assay.Plasma anti-SARS coronavirus IgG antibody was not detected in normal subjects and the clinical personnel. After 0-7 days, 8-10 days, 11-14 days, 15-20 days of onset of disease, the positive rates were 0.33%, 52%, 86% respectively, and the general positive rate was 61%.The specificity and sensitivity of ELISA to detect plasma anti-SARS IgG antibody were satisfactory. Cases with positive reaction could be diagnosed as patients already infected by the virus. The specific IgG antibody didn't emerge in some patients in the early stage of the disease, and the negative results didn't indicate that they were not infected. And follow-up investigation should be made in those patients. Unlike common epidemic infectious diseases, SARS probably hadn't the potentiality of subclinical infection.

To analyze the usage of corticosteroids in the treatment of SARS.The usage of corticosteroids in 43 SARS patients were reviewed. The initial dosage and the highest dosage of prednisolone were investigated.According to the dosage of the early 3 days, the initial dosage was calculated. The initial methyprednisonlone dosage was (170.82 +/- 15.89) mg.d-1, from 48 to 500 mg.d-1. The maximal dosage was (291.44 +/- 37.63) mg.d-1 (48-800 mg.d-1). Four patients recovered without corticosteroides therapy. Initial therapy was kept in 25 cases. Two had hyperglycemia, one of whom died of hyperosmotic coma and renal failure. 14 cases were not responsive and needed to increase the dosage of corticosteroids. 9 of them accepted pulse dosage therapy and acquired good outcome. None in the group had significant side effect. The severity of patients of the two groups had no significant difference. Those of nonresponsiveness had higher dosage and needed longer time to reach stable.Sub-pulse dosage of methyprednisolone was effective for most SARS patients. Those who were less responsiveness might due to their poor sensitiveness to corticosteroids instead of SARS severity. Pulse treatment might be safe in carefully selected patients.

To observe the application and the roles of non-invasive positive pressure ventilation (NIPPV) in the treatment of severe acute respiratory syndrome (SARS).To analyze retrospectively the data of NIPPV in 105 SARS cases hospitalized from 8 Apr to 14 May, 2003. To generalize the indication, parameter adjustment, treatment effects, side effects and affection rate of the medical faculty.The total number of the patients was 105. Among them 24 patients accepted NIPPV, 5 patients died. The mortality was 4.7%, which was lower than the average rate of our country. The most common side effect was subcutaneous emphysema, of which the incidence rate was 16.7%. There was no SARS affected among the medical faculty during the course of NIPPV.NIPPV is a safe and effective method for the treatment of the severe SARS. The proper application of NIPPV could decrease the chance of the invasive ventilation and decrease the affective rate of the medical faculty.

To observe the radiological features of chest X ray in SARS patients.The chest films of 23 cases of SARS were reviewed in the study. The chest film features and site of lung involvement were studied in early stage, most severe stage and recovery stage. The sequential chest film were evaluated hemiquantitatively. The correlation between the score of lung involvement and clinical course was also studied.The lung involvement was most common in lower lung field and outer zone both in early and acute stage. 91.3% cases had bilateral involvement and 91.2% had multifield involvement (two lung fields involvement is 47.8%, three and four lung fields involvement are both 21.7%). The ill-defined and variable opacities showed to be dominant. The improvement of acute stage lesion in 17 cases is related to the usage and increased dosage of corticosteroid, some cases showed non-parallel with symptom and chest X-ray. Hemiquantitative analysis showed there are 6 cases had second peak in X ray, the mean time of onset is 13.2 days, and lasted for 5.8 days.The chest X ray of SARS has some features and its changes can reflect the clinical situation.

To investigate the clinical characteristics and therapeutic effect in the early stage of patients with Severe Acute Respiratory Syndrome (SARS).A total of 45 clinical diagnosed SARS patients were enrolled in the study.43 (95.6%) of all 45 patients had exposure to SARS patients and the average incubation time was (7.3 +/- 4.7) days (range 2 to 20 days). The clinical features including fatigue (60%), dry cough (68.9%), dyspnea (53.3%), joint pain (26.7%) and diarrhea (26.7%). The laboratory test show that 33% patients with leukopenia and thrombocytopenia, 53.3% with elevated serum aminotransferase and 26.6% with increased creatinine kinase levels. The occurrence of abnormal chest radiographs was (4.2 +/- 2.9) days from the onset, and CT scanning was better than X-ray in the early diagnosis. The average time for the progression and improvement of the chest radiographs were (9.3 +/- 4.1) and (14.5 +/- 5.0) days, respectively. The administration of corticosteroids was started (4.8 +/- 3.5) days from the onset and the maximal dosage using of steroids was (8.4 +/- 3.9) days. There was a significant difference in the dosage of steroid between severe and mild patients [(610.6 +/- 212.4) mg/day vs (268.1 +/- 202.5) mg/day, P0.001)]. The IgG antibody was detected in 22 out of 34 (64.7%) patients and the average time for the occurrence of antibody was (18.2 +/- 6.4) days (range 9-27 days).Exposure to the SARS patients happened in most patients. The most common clinical features were fever and fatigue. The most common laboratory abnormalities were leukopenia and thrombocytopenia. Serum antibody was not detected until on the 9th day of the course of illness; CT is a more sensitive method for detection of the abnormal chest radiographs than regular X-ray test. The early usage of cortiscosteroids was an efficient method for the treatment, and the dosage of steroids should be individualized.

To study the function of leukocyte adhesion molecules in the pathogenesis of Chronic Obstructive Pulmonary Diseases (COPD) and cor pulmonale, and to evaluate the effect of anti-leukocyte-adhesion therapy for cor pulmonale.The positive expression rates of CD(11a), CD(11b), CD(18), CD(54) in peripheral blood were quantitatively analyzed by flow cytometry using monoclonal antibodies in 42 cases of COPD (stable stage), 41 cases of cor pulmonale (stable stage), 24 healthy controls as well as 20 cases of cor pulmonale who had taken huobahua.The expression rates of CD(11a), CD(11b), CD(18), CD(54) in monocytes and CD(11a) in lymphocytes from the COPD group were much higher than those in the control group (P0.05). CD(11a), CD(11b), CD(18), CD(54) in neutrophils and CD(11a), CD(18), CD(54) in monocytes, and CD(18) in lymphocytes in the cor pulmonale group were significantly stronger than those in the control group (P0.05); whereas the positive expression of CDs was greatly reduced in the cor pulmonale patients who had taken huobahua (P0.05). No differences were found in other groups.Upregulation of CD(11a)/CD(18), CD(11b)/CD(18), CD(54) in monocytes, CD(11a)/CD(18), CD(11b)/CD(18), CD(54) in neutrophils and CD(11a)/CD(18), CD(54) in monocytes in cor pulmonale may promote adhesion of leukocytes with endothelial cells, which may play an important role in the pathogenic process. Huobahua may prevent the development of cor pulmonale by down regulating the expression of CDs.