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Magnesium (Mg) is an essential nutrient that participates in various enzymatic reactions and regulates important biological functions. The distribution and reference ranges in China have not been reported in populations more than 45 years old. This study aimed to assess the magnesium status and determine the reference values of plasma Mg, Ca, and Ca/Mg ratios for China’s population more than 45 years old. A total of 2101 people were randomly selected from the China Nutrition and Health surveillance (CNHS) (2015–2017), considering the regional types and monitoring points. Then, 337 healthy individuals were further selected by a series of strict inclusion criteria to explore the reference range. The plasma magnesium and calcium were tested by inductively coupled plasma mass spectrometry (ICP-MS). The suggested reference values for plasma Mg, Ca, and Ca/Mg ratios were 0.75–1.14 mmol/L, 2.17–3.64 mmol/L, and 2.36–3.66, respectively. Taking 0.75 mmol/L as the lower cut-off limit, the prevalence of Mg deficiency was 6.66%, and the average level of plasma magnesium was 0.88 mmol/L for populations older than 45 years in China. In conclusion, this study provides the magnesium status and reference ranges for plasma Mg, Ca, and Ca/Mg ratio for Chinese people over 45 years old. The results of the recommended reference ranges in this study were very similar to our published results in women of reproductive age. Thus, the reference range of plasma magnesium in different populations in China was further improved.

New coronavirus (SARS-CoV-2), which has caused the coronavirus disease 2019 (COVID-19) pandemic, has brought about a huge burden on global healthcare systems. Rapid and early detection is important to prevent the spread of the pandemic. Here, an assay based on CRISPR/Cas13a and catalytic hairpin assembly (CHA), termed as Cas-CHA, was developed for ultrasensitive and specific detection of SARS-CoV-2 RNA. Upon specific recognition of the target, the CRISPR/Cas13a collaterally cleaved a well-designed hairpin reporter and triggered the CHA reaction. Under optimized conditions, the assay detected the SARS-CoV-2 RNA with a wide range of 100 aM to 100 nM and realized a low detection limit of 84 aM. At the same time, the whole detecting process could be completed within 35 min. More importantly, the assay was able to distinguish SARS-CoV-2 RNA from common human coronaviruses and analyze in saliva samples. By the flexible design of crRNA, the assay was expanded to detect other viruses. The clinical sample analysis verified that the proposed assay held a great potential for practical testing.

To analyze the relationship between vitamin D(VitD)-related single nucleotide polymorphism(SNP) and 25-hydroxyvitamin D(25(OH) D) levels and VitD nutritional status.A total of 1507 women of childbearing age aged 18-45 were selected from the sample bank of "2015 Chinese adult chronic disease and nutrition monitoring". Basic information(including region, season, age, height, weight, etc. ) of the subjects was collected. The SNPs related to VitD metabolism were screened, and the improved multiple ligase detection reaction was used for SNP testing. Liquid chromatography tandem mass spectrometry was used to determine the serum 25(OH)D concentration. The effects of genotypes on 25(OH)D level and VitD deficiency were analyzed by generalized linear model and binary logistic regression model, respectively.After adjusting for latitude, region, region type, season and age, CYP2R1 rs12794714, GC rs2282679, GC rs7041 and VDR rs2228570 were associated with serum 25(OH)D levels in women of childbearing age. The risk of VitD deficiency in individuals carrying GG genotype at rs2282679 was significantly higher than that in individuals carrying TT genotype(OR=2.466, 95%CI 1.690-3.598, Plt;0.001), and the risk of VitD deficiency in individuals carrying A allele at rs2228570 was lower than that in individuals carrying G allele(OR_(AA)=0.625, 95%CI 0.446-0.876, P_(AA)=0.006;OR_(GA)=0.661, 95%CI 0.502-0.869, P_(GA)=0.003).The genotype distribution of CYP2R1 rs12794714, GC rs2282679, GC rs7041 and VDR rs2228570 may be related to serum 25(OH)D level or VitD nutritional status of Chinese women of childbearing age.

Although several studies have shown the relationship between magnesium and diabetes, there are few studies regarding the association between magnesium status and prediabetes. This study aimed to examine the association between dietary magnesium intake and the risk of prediabetes in childbearing Chinese women (18–44 years). A total of 1981 participants without diabetes were randomly selected from China Nutrition and Health Surveillance (CNHS) in 2015 by considering the regional types and monitoring points, including 1420 normal fasting glucose (NFG) people and 561 prediabetes cases. The Food Frequency Questionnaire (FFQ) and inductively coupled plasma mass spectrometry (ICP-MS) measured dietary and plasma magnesium. The results of this study showed that dietary magnesium intake was inversely associated with fasting plasma glucose. For every 100 mg of magnesium intake, there was a 0.052 mmol/L (95% CI 0.019, 0.085) reduction in fasting plasma glucose (p = 0.002). Compared with the lowest intake quartile (

Introduction: Clinically, rat bite fever (RBF) is a condition caused by Spirillum minus or Streptobacillus moniliformis infections, following rat or any rodent bite. In the absence of a rat bite, this condition cannot be accurately diagnosed. Here, we report the first case of RBF due to S. moniliformis but without a rat bite in China. Case Presentation: A 77-year-old woman with reactive arthritis was admitted to the hospital due to high fever. Initially, we suspected reactive arthritis with liver function deterioration. However, we isolated a bacterium which was confirmed to be S. moniliformis using Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Subsequently, the patient was given targeted anti-infective treatment, which completely resolved the symptoms. The patient was discharged upon fully recovery. Conclusions: Rat bite fever infection caused by S. moniliformis may occur without actual rodent bite. MALDI-TOF MS may be applied to determine the diagnosis of RBF. Difficulties in pathogen and clinical diagnosis highlight the need for discovering the complete exposure history and a greater understanding of this rare zoonotic infections.

High iron stores have been reported to be associated with type 2 diabetes mellitus (T2DM). However, evidence for the associations of iron metabolism with T2DM is inconsistent, and whether there is a threshold effect remains controversial. In the present study, we aimed to examine the associations between various iron biomarkers and the risk of T2DM as well as impaired glucose metabolism (IGM) and hyperglycemia in Chinese women of childbearing age. A total of 1145 women were divided into three groups (normal blood glucose metabolism group; IGM group; T2DM group). Biomarkers of iron metabolism (serum ferritin (SF), transferrin, soluble transferrin receptor (sTfR), transferrin saturation, serum iron, total body iron, and sTfR-to-lgferritin index) were measured. After adjusting for various confounding risk factors, SF and sTfR were positively associated with the risk of IGM (fourth vs. first quartile: SF odds ratio (OR) = 1.93 (95% CI 1.17–3.20) and sTfR OR = 3.08 (95% CI 1.84–5.14)) and T2DM (SF OR = 2.39 (95% CI 1.40–4.06) and sTfR OR = 3.84 (95% CI 2.53–5.83)). There was a nonlinear relationship between SF and risk of T2DM and hyperglycemia (p for nonlinearity < 0.01). Our findings suggested that SF and sTfR could be independent predictors of T2DM risk.

Objective: To analyze the associations between serum 25(OH)D levels and the risk of metabolic syndrome (MetS) and its components, and the related genetic and non-genetic factors in non-diabetic women of childbearing age in China. Methods: Subjects were randomly selected from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. The data of sociodemographic characteristics and lifestyle factors were obtained through questionnaire survey. Anthropometry was measured by trained interviewers, and fasting blood was collected to test 25-hydroxyvitamin D [25(OH)D], total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), and other related parameters. Generalized linear mode and multivariate logistic analysis were performed to analyze the associations between serum 25(OH)D and MetS and its components, adjusting for the possible confounders. Results: Body mass index (BMI), serum alanine aminotransferase (ALT), hypersensitive C-reactive protein (hs-CRP), 25(OH)D, phosphorus (P), and parathyroid hormone (PTH) levels were associated with the number of MetS’s components. G allele carriers of GC rs2282679 had higher diastolic blood pressure (DBP) and FBG levels compared with the TT genotypes, while higher genetic risk score (GRS) seemed to be associated with reduced HDL-C level. The odds ratio (OR) for MetS in lowest group of 25(OH)D was 1.533 (0.980–2.399) after adjusting for season, district, area type, latitude, age, BMI, PTH, P, ALT, CRE, interleukin-6 (IL-6), and hs-CRP, compared with the median group, but the association was not significant. An insufficient 25(OH)D concentration (

To analyze the iodine nutritional status and related factors of mothers with children under 2 years old, we collected data from the 2016–2017 National Nutrition and Health Surveillance of Children and Lactating Women. A total of 1311 mothers from Hebei, Zhejiang, and Guangxi province were included in the study. Urinary iodine concentration (UIC), thyroid-stimulating hormone (TSH), body mass index (BMI), vitamin A (VA), and vitamin D (VD) were measured. The distributions of UIC and TSH were assessed. Relationships between UIC, TSH and the possible factors were analyzed. The median UIC (MUIC) (P25-P75) of total mothers and mothers in lactation was 142.00 µg/L (99.10-209.40 µg/L) and 139.95 µg/L (96.22-208.03) µg/L, respectively. No differences in UI were found between breastfeeding mothers and non-breastfeeding mothers. The prevalence of mothers with UICs P 300 µg/L. Region, area type, age, BMI, VA, or VD should be taken into consideration in the future iodine evaluation and surveillance.

Early screening of diabetic kidney disease (DKD) remains a major challenge. Our aim was to evaluate the value of urinary orosomucoid 1 protein (UORM1) in early renal impairment screening in type-2 diabetes patients.The concentration of UORM1, the UORM1-to-creatinine ratio (UORM1CR), the urinary albumin-to-creatinine ratio (ACR), the alpha-1-microglobulin-to-creatinine ratio (A1MCR) and estimated glomerular filtration rate (eGFR) were measured in 406 type-2 diabetes patients. Any positive values for ACR, A1MCR and/or eGFR were considered as indicative of renal impairment.On average, the levels of UORM1 and UORM1CR were about seven times higher in subjects with renal injury than in those without. Both UORM1 and UORM1CR, when adjusted via logarithm-transformation, were significantly related to ACR, A1MCR and eGFR levels. The highest correlation was observed between UORM1CR and A1MCR (r = 0.85, P .001). The cut-off values for UORM1 (2.53 mg/L) and UORM1CR (3.69 mg/g) for the early diagnosis of kidney impairment were obtained from receiver operating characteristic curves. UORM1CR obviously had higher diagnostic efficiency corresponding to 83.26% sensitivity and 90.32% specificity than UORM1. Likewise, its sensitivity was higher than those of ACR, A1MCR and eGFR. Bad glycaemic control had the highest risk of increased UORM1CR (odds ratio [OR] = 2.81, P .001), while high HDL-C (high-density lipoprotein cholesterol) decreased the risk of increased UORM1CR (OR = 0.38, P = .017).The UORM1CR (3.69 mg/g) has the high diagnostic efficiency for the early screening of renal impairment in type-2 diabetes patients. Furthermore, good glycaemic control and high HDL-C might be protective factors against UORM1CR increase.

Objectives Numerous biomarkers have been shown to be associated with albuminuria. However, few of them are valuable separate predictors of albuminuria development. This study aimed to develop a model for predicting the short-term risk of new-onset albuminuria in normoalbuminuric patients with type 2 diabetes (T2D). Methods 213 patients with T2D who were normoalbuminuric at the baseline were enrolled in this study. Basal levels of clinical characteristics and renal biomarkers including urinary orosomucoid (alpha-1-acid-glycoprotein, UORM), neutrophil gelatinase-associated lipocalin, retinol-binding protein, alpha-1-microglobulin, transferrin, and albumin-to-creatinine ratio (ACR) were utilized to analyze the association with the short-term risk of new-onset albuminuria. Results 19.72% of normoalbuminuric subjects at baseline progressed to albuminuria over the 2-year follow-up period. Except for NGAL, the basal levels of the other five renal biomarkers were significantly associated with new-onset albuminuria risk in the univariate analysis. In the multivariate logistic regression analysis using Forward: LR method, a model incorporating UORM/Cr, ACR, and HbA1c was established. Comparatively, this model had a higher potential to predict new-onset albuminuria risk compared with the single use of renal markers. In the validation of this model performed by 5-fold cross-validation method, the accuracy of this model was 0.818 ± 0.008 in the training sets, 0.827 ± 0.062 in the test sets, indicating a good capability for assessing albuminuria risk. Finally, a nomogram based on this model was constructed to facilitate its use in clinical practice. Conclusion The combined analysis of UORM/Cr, ACR and HbA1c may be of potential value for predicting the short-term risk of new-onset albuminuria in such patients.

Circular RNAs (circRNAs) are aberrantly expressed in the brain and play a role in a variety of central nervous system diseases. However, the essential role and therapeutic potential of circRNAs in ischemic stroke (IS) are poorly understood. Here, using circRNA sequencing, we showed that circRNA homeodomain-interacting protein kinase 3 (circHIPK3) was abundantly expressed in ischemic brain tissues in transient middle cerebral artery occlusion (tMCAO)-evoked stroke model mice. Knockdown of circHIPK3 markedly reduced the infarct volume, brain water content, neurological deficit scores, and blood-brain permeability and ameliorated brain microvascular endothelial cell (BMEC) apoptosis and mitochondrial dysfunction in tMCAO mice. Gain- and loss-of-function experiments were performed to verify the effects of miR-148b-3p on oxygen-glucose deprivation (OGD)-induced BMEC apoptosis and mitochondrial dysfunction. Mechanistically, circHIPK3 functions as an endogenous sponge of miR-148b-3p to decrease its activity, resulting in upregulation of CDK5R1 and CDK5 expression, downregulation of SIRT1 expression and subsequent BMEC apoptosis and mitochondrial dysfunction. Collectively, our findings suggest that circHIPK3 and its coupling mechanism are implicated in IS, providing translational evidence that circHIPK3 could be a key therapeutic target for IS.

Streptococcus suis (S. suis) is a zoonotic pathogen that primarily inhabits the upper respiratory tract of pigs. Therefore, pigs that carry these pathogens are the major source of infection. Most patients are infected through contact with live pigs or unprocessed pork products and eating uncooked pork. S. Suis mainly causes sepsis and meningitis. The disease has an insidious onset and rapid progress. The patient becomes critically ill and the mortality is high. In this case report, we described a rare case of S. suis isolated from a middle-aged woman in Jinhua City, Zhejiang Province, China, who did not have any contact with live pigs and had not eaten uncooked pork. S. Suis was isolated from both the patient's blood and cerebrospinal fluid samples.

To investigate the association of rs7041 polymorphism of GC gene that encodes the vitamin D-binding protein with serum vitamin D status in Chinese women of childbearing age.A total of 1812 plasma samples of women childbearing aged 18-44 years old were selected by stratified random sampling technology from the established biological samples bank of Chinese Chronic Diseases and Nutrition Survey(CCDNS, 2015-2018). The serum 25(OH)D status was detected by enzyme-linked immunosorbent assay. The genotypes of rs7041 in the GC gene were analyzed by improved multiple ligase detection reaction method.A total of 1812 childbearing women aged 18-49 years were included in this study. The frequency of rs7041 genotypes in the study were distributed according to the Hardy-Weinberg equilibrium, indicating sufficient representativeness of our sample. The median serum 25(OH)D status was 16. 69(12. 04, 21. 69)ng/mL. The higher 25(OH)D levels was detected in the overall sample, southern women or women with normal vitamin D status with the CC genotype than the AA genotype(Plt;0. 05). Before and after correction, the risk of vitamin D insufficiency in the women carrying the CC genotype was decreased significantly compared with the women carrying the AA genotype(OR=0. 571, 95%CI 0. 373-0. 873). And the CC genotype of rs7041 was associated with a significant decrease in risk of 25(OH)D deficiency(in the subgroup of southern childbearing women, OR=0. 284, 95%CI 0. 144-0. 560 and in the subgroup of northern childbearing women, OR=0. 109, 95%CI 0. 015-0. 798).The GC rs7041 with A/C polymorphism are significantly correlated with 25(OH)D status in Chinese childbearing women, mutant CC genotype is a protective factor for vitamin D non-normal status risks.

We evaluated the iodine nutritional status and related factors among school-age children based on the 2016 National Nutrition and Health Surveillance of Children and Lactating Women, 3808 children from Hebei, Guangxi, and Zhejiang province were included in the study. Urinary iodine concentration (UIC), thyroid-stimulating hormone (TSH), body mass index (BMI), vitamin A (VA), and vitamin D (VD) were measured. The abnormal rate of UIC and TSH were assessed. Relationships between UIC/TSH and the possible factors were analyzed. The overall median UIC was 185.14 µg/L, and the median UIC of children aged 8–10 was 164.60 µg/L. Prevalence of iodine deficiency and excess was 13.84% and 14.36%, respectively, and 12.87% of children showed TSH excess. UIC, as well as the abnormal rates of iodine deficiency (ID) and TSH, were significantly different among the three provinces. The median UICs and excess rates increased with age, reaching 211.45 µg/L and 21.35% at age of 14~, while TSH showed the opposite trend. Overweight children tended to have lower UIC and higher TSH. Higher UIC and TSH were found in VA sufficient group (p &lt, 0.01). Further, the VD deficient group had a higher TSH compared to the sufficient group (p &lt, 0.01). Moreover, UI and TSH distribution was obviously different among different vitamin A/D status (p &lt, 0.05). Although the median UIC of school-age children was optimal, there were pockets of inadequate and excessive UI in the three provinces. Compared to the national IDD monitoring results in 2014, the iodine nutritional status of children was greatly improved. Considerations of region, age, BMI, VA, or VD are needed in the future iodine evaluation and surveillance.

The widespread use of cyclophosphamide (CP) in medical treatment had caused ubiquitous contamination in the environment. To data, many studies have been carried out on the toxic effect of CP. However, among these toxic effects of CP, which are the most sensitive remains unclear. Present study aimed to investigate the toxicity of CP on mice and evaluate the sensitivity of physiological-biochemical parameters upon exposure of mice to CP. Results showed that as compared with the control group, CP caused significant reduction in body weight (p leukocyte density > ALT in kidney > spleen coefficient; while among the stimulated parameters, the sensitivity was ranked as MDA (liver) > Cr (kidney) > ALT (liver). Overall, the most sensitive parameters to CP toxicity may be associated with growth, immune system and the normal function of liver and kidney.

AIM Various studies have reported that urinary neutrophil gelatinase-associated lipocalin (NGAL), an indicator of tubular damage, may be an effective biomarker of renal impairment in patients with diabetes. This study aimed to compare the ability of urinary alpha-1-microglobulin (a traditional tubular damage marker) with NGAL for evaluating renal insufficiency in patients with type-2 diabetes. METHODS Urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used to determine whether 513 participants with type-2 diabetes had renal dysfunction. Urinary alpha-1-microglobulin-to-creatinine ratio (A1MCR) and NGAL-to-creatinine ratio (NCR) were calculated. RESULTS Although both A1MCR and NCR were significantly higher among participants with renal insufficiency than among participants without renal damage, the difference in A1MCR values between participants with and without renal insufficiency was relatively greater than the difference in NCR values, especially among the male subjects. The correlation of ACR or eGFR with A1MCR was stronger than that of ACR or eGFR with NCR. A1MCR showed a good capability for detecting renal dysfunction (area under the curve = 0.80), its cut-off value was 14.82 mg/g, corresponding to 71.4% sensitivity and 73.1% specificity. The diagnostic efficiency of A1MCR was significantly higher than that of NCR. CONCLUSION The results indicated that the traditional tubular damage marker A1MCR was more significantly associated with renal insufficiency defined by ACR and/or eGFR and may have a higher diagnostic efficiency compared with the efficiency of NCR in patients with type-2 diabetes.

Highlights The level of urinary α1 -microglobulin to creatinine ratio (A1MCR) increases with longer diabetes duration. Patients with a diabetes duration >14 years have a higher tubular damage rate. Being male and a diabetes duration >14 years have an interaction effect on increased A1MCR.

Background There is no worldwide recognized reference system and standard for urinary albumin measurement until now, so the analytical quality from different laboratories has always varied. In this study, we aimed to evaluate the analytical performance of a urinary albumin assay system using Sigma-metric, and thereby choose a suitable control rule to guarantee the analytical quality of the assays. Method Two levels of diluted reference material (ERM-DA47OK/IFCC) were used to calculate the biases, the coefficient of variation (CV) were calculated from six months of internal quality control measurements at two levels, and the external quality assessment standard of China for urinary albumin (30%) was used as the total allowable error(TEa). Results The Sigma values for quality control levels 1 and 2 were 4.28 and 6.14, leading to recommended Westgard rules of 13s/22s/R4s/41s (N = 2, R = 2) and 13s(N = 2, R = 1), respectively. Westgard rule 13s/22s/R4s/41s(N = 2, R = 2) was selected for the quality control of the urinary albumin measurements, and with it, the power function graph showed a high efficacy for determining the detection errors with a probability of false rejection of 1.004% and a probability of error detection of 98.80%. Conclusion With a TEa of 30% recommended by the external quality assessment standard of China, Westgard rule 13s/22s/R4s/41s(N = 2, R = 2) with a high efficacy for determining the detection error is recommended for the quality control of urinary albumin measurements.

Objectives Mortality associated with carbapenemase-producing Enterobacteriaceae is high as there are few therapeutic options. Escherichia coli sequence type 410 (ST410) is currently an international high-risk clone and is responsible for a large number of clinical infections. Here we report the draft genome sequence of a ST410 clinical E. coli isolate (ECS9) co-harbouring blaNDM-5, blaOXA-1, blaCTX-M-15, blaCMY-2, aac(3)-IIa and aac(6')-Ib-cr genes, obtained from a patient with bloodstream infection in China. Methods The genome of E. coli ECS9 was sequenced using an Illumina HiSeqTM 4000 instrument with a 150-bp paired-end approach. Generated sequence reads were assembled using Velvet 1.2.10. Contigs were annotated using Rapid Annotation using Subsystem Technology (RAST), and further whole-genome sequence data analyses were performed. Results Escherichia coli ECS9 belongs to multilocus sequence typing (MLST) ST410. The total number of assembled bases was 4 935 145 bp, with 5077 protein-coding sequences. The presence of the blaNDM-5, blaOXA-1, blaCTX-M-15 and blaCMY-2 genes was detected in addition to other antimicrobial resistance genes conferring resistance to fluoroquinolones, aminoglycosides, trimethoprim, sulfonamides and tetracyclines. Conclusion To our knowledge, this is the first report of anE. coli ST410 strain co-harbouring blaNDM-5, blaOXA-1, blaCTX-M-15, blaCMY-2, aac(3)-IIa and aac(6')-Ib-cr, obtained from a bloodstream infection in China. The presented genome sequence of carbapenemase-producing E. coli strain ST410 could provide further insight into the acquisition of multiple resistance genes by this successful lineage.

The prevalence and clinical risk factors of normoalbuminuric renal impairment have not yet been investigated in elderly Chinese populations. To clarify this, we conducted survey research on an elderly Chinese community population.A total of 691 elderly community participants were included in this study. Normoalbuminuria was defined as a urinary albumin to creatinine ratio (ACR)30 mg/g in morning urine. The estimated glomerular filtration rate (eGFR) and urinary alpha-1-microglobulin to creatinine ratio (MCR) were evaluated to assess normoalbuminuric kidney impairment in this elderly population.Among the whole cohort, 30.25% had albuminuria, 8.68% showed reduced eGFR and 49.78% had increased MCR. Normoalbuminuric subjects also showed a high prevalence of low eGFR and increased MCR (6.02% for reduced eGFR and 37.55% for increased MCR). Among the normoalbuminuric participants, the highest prevalence of increased MCR was found in the subjects with diabetes (50%), whereas the highest prevalence of low eGFR was found in women (8.11%). There was no significant difference in ln-MCR values between normoalbuminuric subjects with eGFR60 and 60 ml/min/1.73 mAlbuminuria may have limited utility as a screening marker of renal injury, as a considerable proportion of the elderly population have renal impairment despite normoalbuminuria. Rather than focusing solely on patients with diabetes or hypertension, normoalbuminuric renal impairment should be given more attention within the overall elderly population.

Acrylamide, exists in carbohydrate-rich food heated at high temperatures, is a probable carcinogen to humans. Excessive alcohol intake can also lead to a variety of pathological changes in the body. Acrylamide in the foods and alcohol in the drinks are unavoidable. And studies have demonstrated that combination of the two substances which are taken into the body via diet may cause adverse effects in the cells, even induce impairments on testicular spermatogenesis in male offsprings. Both acrylamide and alcohol are mainly metabolized in the liver, where cytochrome P450 2E1 (CYP2E1) acts as the common metabolic enzyme of the two xenobiotics. This study aimed to explore the effects of acrylamide and alcohol combination on rat hepatoma BRL cells proliferation and the probable mechanisms. MTT, western blotting, EdU fluorescence staining, flow cytometry and PCR were used. Results showed that combination of acrylamide and alcohol at low doses promoted BRL cells proliferation through CYP2E1/Akt/ NF-κB/cyclinB1/cyclinD1 activation and ROS production. The combined effects of acrylamide and alcohol largely depended on ROS level. Furthermore, acrylamide and alcohol could synergistically induce miR-21, which was related to the progress of liver regeneration. These data showed that combination of acrylamide and alcohol at low doses promoted BRL cells proliferation through inducing ROS production, which indicated that intake of fried starch food with small dose of alcohol might have positive effects on liver regeneration.

BACKGROUND Accurate detection of urine albumin is important for evaluating the progression of diabetic kidney disease. However, two levels of daily quality control may not be practically feasible in some small clinical laboratories owing to a small number of patient samples and high costs. We aimed to prepare homemade quality control material (HQM) to measure urine albumin and then verify its performance. METHODS Normal saline solution and fresh mixed urine samples from five donors with serious kidney disease were used to prepare two levels of HQM (HQM1 and HQM2). Anhydrous ethylene glycol and sodium azide were used as antifreeze and as a preservative, respectively. RESULTS Before being separated into Eppendorf tubes, 20 tests for HQM1 and HQM2 were performed, resulting in mean ± SD of 19.52 ± 0.91 mg/L and 105.28 ± 3.71 mg/L, respectively. After having been divided, the vial-to-vial variations of HQM1 and HQM2 were small (4.93% and 3.70%, respectively). The stability of HQM1 and HQM2 stored at 2 - 8°C was about 2 months and 80 days, respectively, and when stored at -20°C, remained stable for more than 8 months. After 1 - 8 months of cryopreservation at -20°C, once opened, the HQM in every Eppendorf tube could be kept for at least five days (CV < 6.1%). CONCLUSIONS Our HQM stored at -20°C remained stable for a long time, and so could be considered as an alternative to standard QMs in the clinical laboratory.

Reactivation of tumor suppressor genes by nontoxic bioactive food component represents a promising strategy for cancer chemoprevention. Retinoic acid receptor β (RARβ), one member of the RAR receptor family, is considered as a tumor suppressor. Reduced expression of RARβ has been reported in lung cancer and other solid tumors. DNA hypermethylation of the promoter region of RARβ is a major mechanism for its silencing in tumors. Recently, curcumin has been considered as a potential DNA methyltransferase inhibitor. Herein, we demonstrated that curcumin significantly elevate RARβ expression at the mRNA and protein levels in tested cancer cells. Additionally, curcumin decreased RARβ promoter methylation in lung cancer A549 and H460 cells. Mechanistic study demonstrated that curcumin was able to downregulate the mRNA levels of DNMT3b. In a lung cancer xenograft node mice model, curcumin exhibited protective effect against weight loss because of tumor burden. Tumor growth was strongly repressed by curcumin treatment. As the results from in vitro, RARβ mRNA were increased and DNMT3b mRNA were decreased by curcumin treatment compared with the mice in control group. Altogether, this study reveals a novel molecular mechanism of curcumin as a chemo-preventive agent for lung cancer through reactivation of RARβ.

BACKGROUND: A direct correlation between hepatitis B virus DNA (HBV‐DNA) and liver markers has not been identified in chronic hepatitis B (CHB) patients. However, the effect of HBV‐DNA changes on liver markers remains unclear. We explored the association between decreased HBV‐DNA and liver makers in CHB patients. METHODS: Chronic hepatitis B patients who visited Jinhua Central Hospital twice were selected for analysis. Finally, 171 participants with a 1‐log reduction in HBV‐DNA between the two visits were enrolled as the case group, and 158 participants with no significant changes in HBV‐DNA were enrolled as the control group. RESULTS: There was no significant correlation between HBV‐DNA and liver markers (P>.05). However, in longitudinal analysis, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma‐glutamyl transpeptidase (GGT) were significantly different between the two tests (P26 times, ALT was reduced by half or more. A similar trend was observed with a decrease of >63 times for AST and a decrease of >76 times for GGT. CONCLUSIONS: A large change in HBV‐DNA can lead to a significant variation in liver markers. In particular, ALT was more sensitive than other liver markers to a reduction in HBV‐DNA.

Acrylamide, a proven rodent carcinogen, is present in carbohydrate-rich food heated at high temperatures. It can be metabolized into glycidamide mainly by cytochrome P450 2E1 (CYP2E1). The fact that acrylamide is a potential carcinogen to human-beings draws public attention recently. This study aimed to elucidate the effect of acrylamide at low doses on proliferation of HepG2 cells, and to test whether the two well-studied chemopreventive agents, curcumin and (−)-epigallocatechin-3-gallate (EGCG), would have antagonistic effects against acrylamide. The results showed that lower concentration of acrylamide (⩽100 μM) significantly increased the proliferation of HepG2 cells, but not of the other cancer cells (MDA-231, HeLa, A549, and PC-3). Only in HepG2 cells, low concentration of acrylamide was able to induce CYP2E1 expression significantly. Knockdown of CYP2E1 restrained acrylamide to increase viability of HepG2 cells. In addition, acrylamide raised expression of epidermal growth factor receptor (EGFR), cyclin D1 and nuclear factor-κB (NF-κB), which contributed to cell proliferation. Both curcumin and EGCG effectively reduced acrylamide-induced proliferation, as well as protein expression of CYP2E1, EGFR, cyclin D1 and NF-κB. All these results suggest that low concentration of acrylamide may contribute to progression of hepatocellular carcinoma (HCC). Curcumin or EGCG could prevent acrylamide triggering this effect.

Acrylamide, a potential carcinogen, exists in carbohydrate-rich foods cooked at a high temperature. It has been reported that acrylamide can cause DNA damage and cytotoxicity. The present study aimed to investigate the potential mechanism of human hepatocarcinoma HepG2 cell proliferation induced by acrylamide and to explore the antagonistic effects of a natural polyphenol curcumin against acrylamide via miR-21. The results indicated that acrylamide (≤100 μmol/L) significantly increased HepG2 cell proliferation and miR-21 expression. In addition, acrylamide reduced the PTEN expression in protein level, while induced the expressions of p-AKT, EGFR and cyclin D1. The PI3K/AKT inhibitor decreased p-AKT protein expression and inhibited the proliferation of HepG2 cells. In addition, curcumin effectively reduced acrylamide-induced HepG2 cell proliferation and induced apoptosis through the expression of miR-21. In conclusion, the results showed that acrylamide increased HepG2 cell proliferation via upregulating miR-21 expression, which may be a new target for the treatment and prevention of cancer.

The association between dietary carbohydrate intake, glycemic index (GI) and glycemic load (GL), and risk of gastric cancer (GC) has been investigated by many studies. However, the results of these studies were controversial. The aim of our study was to systematically assess this issue. PUBMED and EMBASE were searched up to March 2015, and either a fixed- or a random-effects model was adopted to estimate overall relative risks (RRs). Dose–response, meta-regression, subgroup, and publication bias analyses were applied. Twenty-six studies with approximately 540,000 participants were finally included in this meta-analysis. High level of dietary carbohydrate intake (pooled RR 1.17, 95 % CI 0.91–1.50), GI (pooled RR 1.17, 95 % CI 0.80–1.69), and GL (pooled RR 1.06, 95 % CI 0.90–1.26) were all nonsignificantly associated with incidence of GC. In addition, no significant dose–response relationship was observed between carbohydrate intake, GI and GL, and the risk of GC. However, further subgroup analyses based on gender and geographic region suggested a significant association between higher carbohydrate intake (pooled RR 1.52, 95 % CI 1.10–2.08), GL (pooled RR 1.41, 95 % CI 1.04–1.92), and GC risk in males subgroup, and between higher carbohydrate intake (pooled RR 1.69, 95 % CI 1.36–2.09) and GC risk in Asian studies. No significant association was found between dietary carbohydrate intake, GI and GL, and risk of GC. However, significantly positive association was observed in the males subgroup and Asian studies.

Background Nonstructural protein 1 (NS1) Ag-based tests are useful for detecting dengue virus (DENV), but there is lack of evidence on the diagnostic accuracy of NS1 Ag-based tests in Asian population. Thus, we conducted this meta-analysis to obtain the overall estimated and summarized performance of the NS1 Ag-based tests in the detection of DENV in Asia. Methods PubMed, Embase and Medline were searched for studies that evaluated the diagnostic validity of NS1 Ag-based tests between January 1990 and November 2014. Data were analyzed by Meta-Disc and STATA software. Results A total of 18 studies including 3342 dengue cases and 1904 control cases which fulfilled the inclusion criteria were considered for analysis. The pooled sensitivity and specificity for NS1 Ag-based tests was 66 % (95 % CI 64.5–67.5) and 97.9 % (95 % CI 97.3–100), respectively. STRIP has the overall highest sensitivity (72.9 %, 95 % CI 70.1–75.5). According to viral serotype, the test with the highest sensitivity for DENV1, DENV2 and DENV3 were Platelia (83.7 %, 95 % CI 79.7–87.1), Panbio (71.8 %, 95 % CI 65.5–80.9) and STRIP (81.9 %, 95 % CI 75.5–87.2) respectively. The highest sensitivity for primary infection was Platelia (95.1 %, 95 % CI 92.6–96.9) and for secondary infection was STRIP (64 %, 95 % CI 53.2–73.9). Conclusion Our meta-analysis suggests that NS1 Ag-based test is a good diagnostic method for DENV with a high specificity. However, viral serotype, serological status, clinical severity and the duration of illness are the main factors influencing the diagnostic accuracy.

Gastric cancer is one of the most common malignancies worldwide. Interleukin‐1‐beta (IL‐1β) is a pro‐inflammatory cytokine and potent inhibitor of gastric acid secretion. Some studies provided evidence of the association between IL‐1B 31 polymorphism and gastric cancer risk while other studies did not. Therefore, we conducted a comprehensive meta‐analysis to reassess the association. A systematic literature search of the PubMed and EMBASE databases identified 37 studies with 6108 cases and 8980 controls for this meta‐analysis. The crude odd ratios (ORs) and the 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Meta‐regression was used to determine the major source of heterogeneity across the studies. The pooled analysis did not suggest the significant association of IL‐1B 31 C>T polymorphism with gastric cancer risk. Stratified analysis was performed by ethnicity, source of control, genotype method, and indicated a significantly increased gastric cancer risk associated with IL‐1B 31T variant in the population‐based subgroup (heterozygous model: OR = 1.22, 95% CI = 1.03–1.45). Moreover, stratified analysis by Helicobacter pylori infection status indicated that IL‐1B 31 polymorphism increased gastric cancer risk in infection‐positive subgroup (homozygous model: OR = 1.35, 95% CI = 1.02–1.78; heterozygous model: OR = 1.31, 95% CI = 1.04–1.66; recessive model: OR = 1.29, 95% CI = 1.04–1.61). The study suggested that IL‐1B 31 polymorphism might confer susceptibility to gastric cancer in the presence of H. pylori infection, indicating a gene–environment interaction in gastric carcinogenesis.

Reactivation of tumor suppressor genes by nontoxic bioactive food component represents a promising strategy for cancer chemoprevention. Retinoic acid receptor β (RARβ), one member of the RAR receptor family, is considered as a tumor suppressor. Reduced expression of RARβ has been reported in lung cancer and other solid tumors. DNA hypermethylation of the promoter region of RARβ is a major mechanism for its silencing in tumors. Recently, curcumin has been considered as a potential DNA methyltransferase inhibitor. Herein, we demonstrated that curcumin significantly elevate RARβ expression at the mRNA and protein levels in tested cancer cells. Additionally, curcumin decreased RARβ promoter methylation in lung cancer A549 and H460 cells. Mechanistic study demonstrated that curcumin was able to downregulate the mRNA levels of DNMT3b. In a lung cancer xenograft node mice model, curcumin exhibited protective effect against weight loss because of tumor burden. Tumor growth was strongly repressed by curcumin treatment. As the results from in vitro, RARβ mRNA were increased and DNMT3b mRNA were decreased by curcumin treatment compared with the mice in control group. Altogether, this study reveals a novel molecular mechanism of curcumin as a chemo-preventive agent for lung cancer through reactivation of RARβ.

Ubiquitin activating enzyme E1-like (UBE1L) is the activating enzyme for ISG15ylation (ISG15, interferon stimulated gene 15). UBE1L is thought to be a candidate tumor suppressor gene and has positive activity against stress responses such as viral infections. Both type I interferon and retinoic acid are known to induce UBE1L expression. However, the molecular mechanism of UBE1L regulation is unclear. Here, the effect of several chemopreventive polyphenols on UBE1L expression in human bronchial epithelial cells (Beas-2B) was investigated. Lower concentrations of curcumin, (-)-epigallocatechin-3-gallate (EGCG) and resveratrol upregulated UBE1L, while high concentrations of curcumin, EGCG and resveratrol downregulated UBE1L levels. Interestingly, curcumin, EGCG and resveratrol diminished intracellular reactive oxygen species (ROS) at lower concentrations but generated ROS at higher concentrations. The antioxidant N-acetylcysteine (NAC) increased UBE1L protein levels, while pro-oxidants such as hydrogen peroxide and tert-butyl hydroperoxide (tBHP) decreased UBE1L protein levels, indicating that the intracellular redox status is associated with UBE1L expression. Kinase inhibitors were used to examine the contribution of mitogen-activated protein kinase (MAPK) activity to the polyphenol-regulated UBE1L. Only the inhibition of c-Jun N-terminal kinase (JNK) significantly reduced UBE1L expression. Knockdown of nuclear factor erythroid-2 related factor-2 (Nrf2) caused a concomitant decrease in UBE1L protein levels. It is concluded from the above mentioned results that JNK/Nrf2 signal pathway is involved in the regulation of UBE1L via intracellular ROS status when cells came in contact with polyphenols.