OBJECTIVETo investigate the role of c-Jun N-terminal kinase (JNK) signal transduction pathway in the rats of nonalcoholic fatty liver disease (NAFLD).

METHODSSixty four Sprague-Dawley rats were randomly divided into four groups: 8-week control group (NG8w), 12-week control group (NG12 w), 8-week high-fat diet (HG8w), and 12-week high-fat diet group (HG12w), with 16 rats in each group. Glucose infusion rate (GIR) was tested by euglycemic hyperinsulinemic clamp; aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), free fatty acid (FFAs), fast insulin (FIns), tumor necrosis factor alpha (TNF alpha), superoxide dismutase (SOD) and malondialdehyde (MDA) were tested by biochemistry automatic analyzer or RIA; The expression of JNK1, insulin receptor substrate-1 (IRS-1), phospho-IRS-1 Ser307 (p-IRS-1 Ser307), Protein kinase B (PKB) and phospho-PKB Ser473 (p- PKB Ser473) were detected by Western blot.

RESULTSCompared to control group, body weight, liver index, serum levels of ALT, AST, TG, TC, FIns, FFAs, TNF alpha, and TC, TG FFAs, MDA in liver homogenates were increased, while the level of SOD, and GIR were decreased. The expression of JNK1 protein and p-IRS-1 Ser307 in liver tissue was up-regulated, while expression of p-PKB Ser473 was decreased (P < 0.05). A positive correlation was found between the expression intensity of JNK1 and IR (Pearson correlation: 0.718, P < 0.01).

CONCLUSIONThe high-fat could induce the expression of JNK1, which in turn modulates the phosphorylation of proteins in the insulin signaling pathway, and induces insulin resistant.

Alanine Transaminase ; blood ; Animals ; Biomarkers ; blood ; Dietary Fats ; administration & dosage ; Disease Models, Animal ; Fatty Liver ; etiology ; metabolism ; pathology ; Insulin Receptor Substrate Proteins ; metabolism ; Insulin Resistance ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Lipids ; blood ; Liver ; metabolism ; pathology ; Male ; Proto-Oncogene Proteins c-akt ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction

OBJECTIVETo investigate the blood lead status and influencing factors among preschool children in the sampling city.

METHODStratified-clustered-random sampling was used. Standardized questionnaire and peripheral blood samples were obtained from 69 968 children aged 0-6 years in fixed kindergartens and communities of Yinchuan, Xi'an, Chengdu, Wuhan, Hefei, Beijing, Harbin, Zhengzhou, Huhhot, Shijiazhuang, Haikou, Dalian, Qingdao, Guangzhou, Nanning and Changsha from 2004 to 2008, respectively. Tungsten atomic absorbtion spectrophotometry was employed to determine the blood lead level of children.

RESULTThe proportion of children with blood lead level ≥ 100 µg/L was 7.57% (among which the proportion of high blood lead level, mild lead poisoning, moderate lead poisoning, severe lead poisoning were 91.0%, 2.76%, 3.32%, 2.93%, respectively) and the blood lead level was lower than those of the past studies. The proportion of high blood lead level has steadily declined from 2004 to 2008 [the proportions were 10.03%, 7.85%, 7.40%, 6.91% and 4.78%, respectively (χ(2) = 297.36, P < 0.0001)]. The proportion of children with blood lead level ≥ 100 µg/L in Haikou, Zhengzhou, Guangzhou, Shijiazhuang, Changsha, Xi'an, Wuhan, Hefei, Chengdu, Yinchuan, Harbin, Beijing, Dalian, Huhhot, Nanning and Qingdao were 12.15%, 10.49%, 10.37%, 9.69%, 9.53%, 9.46%, 9.40%, 8.50%, 7.99%, 7.98%, 7.51%, 6.10%, 3.25%, 2.89%, 2.46% and 2.39%, respectively (χ(2) = 768.21, P < 0.0001). By multiple regression method, the risk factors which influenced blood lead status of children were education status of mother, older children, behavior and dietary habit of children, boy, stay for long time in traffic busy areas, the type of housing, taking traditional Chinese and herbal medicine. The protective factors against lead poisoning in children mainly included scattered living, the nutritional status of calcium, iron, zinc, frequent intake of milk, and older mother.

CONCLUSIONThe blood lead level of children has decreased, but is still higher than those in developed countries. Lead exposure remains a public health issue which affects children most. The blood lead level of children is affected by multiple factors. Government and the whole society should pay attention to interrupt the lead pollutant and to promote nutritional health education. With all these efforts, it is possible to stop the progress of lead exposure and reduce its hazardous effects on the growth and development of children.

Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Lead ; blood ; Lead Poisoning ; epidemiology ; Male ; Risk Factors ; Surveys and Questionnaires ; Urban Population

OBJECTIVETo study the pathology characteristics and management of Hangman's fracture combined with intervertebral disc injury.

METHODSTwenty-one patients suffered from this special injury were converged in this study. All patients underwent anterior C(2 - 3) discectomy and fusion, 18 cases were fixed by anterior cervical plate. The type of fractures, radiology characteristics, and clinical outcomes were investigated.

RESULTSNo graft displacement or absorption, infection and neurologic deterioration occurred. All fresh dislocation of axis and C(2 - 3) angulation were corrected. Fusion of C(2 - 3) intervertebral space and pedicle fracture were acquired in all of the patients. After a mean follow-up of 31 months, ranging from 8 to 48 months, nearly all of the complains disappeared after operation.

CONCLUSIONSHangman's fracture is not restricted at pedicle of the axis. Fracture combined with intervertebral disc injury is a special type of Hangman's fracture. Anterior discectomy and fusion of C(2 - 3) intervertebral disc is an effective operation method in accord with the pathophysiology of this special injury.

Adult ; Axis, Cervical Vertebra ; Bone Transplantation ; methods ; Cervical Vertebrae ; injuries ; surgery ; Diskectomy ; methods ; Female ; Follow-Up Studies ; Humans ; Intervertebral Disc ; injuries ; surgery ; Male ; Middle Aged ; Spinal Fractures ; complications ; diagnosis ; surgery ; Spinal Fusion ; methods ; Traction ; Treatment Outcome

BACKGROUNDThe adverse health effects of lead for children under 6 years are well known. Studies to assess the lead exposure among children in China are small in sample size and lack of national representative data. The aim of this study therefore was to describe blood lead levels and identify risk factors for lead exposure among children aged 0 to 6 years living in 16 cities in China.

METHODSWe analyzed data from blood lead levels surveillance in China carried out in 16 large cities between 2004 and 2008. A stratified clustered random sampling strategy was used. A total of 69 968 children aged 0 to 6 years were included. We conducted multiple Logistic regression analyses to explore risk factors to high blood lead level.

RESULTSThe geometric mean blood lead level of the children was 4.50 µg/dl (median: 4.90 µg/dl; IQR: 3.20 - 7.00 µg/dl). Overall prevalence of blood lead level ≥ 10.00 µg/dl among 0- to 6-year-old children was 7.57%. But the proportion of blood lead level ≥ 5.00 but < 10.00 µg/dl was 42.12%. Blood lead levels were significantly higher in boys (4.63 µg/dl) than in girls (4.35 µg/dl) (P < 0.0001). The geometric mean blood lead levels and prevalence of blood lead level ≥ 10.00 µg/dl increased with age (P < 0.0001 for the two trends). After controlling for sociodemographic, dietary and behavior factors, multivariable analysis indicated that lower maternal education, male gender, younger age, often biting pencil or/and toys, walking or playing for long time on the street, not washing hands before eating are major risk factors for higher lead levels.

CONCLUSIONSThe blood lead levels among Chinese children in urban areas are lower than previous studies but close to those of developed countries. However, children with low lead exposure account for almost half and the sociodemographic factors (age, male sex, and low mother education level) continue to be associated with higher blood lead levels.

Child, Preschool ; China ; Female ; Humans ; Infant ; Infant, Newborn ; Lead ; blood ; Logistic Models ; Male ; Time Factors ; Urban Health

OBJECTIVE: To observe the inhibitory effect of Shenbai Jiedu Fang (SBJDF, a compound recipe of traditional Chinese herbal drugs) on chemically induced carcinogenesis of colorectal adenoma in mice and explore the role of PTEN/PI3K/AKT signaling pathway in mediating this effect. METHODS: Four-week-old male C57BL/6 mice were randomly divided into control group (n=10), AOM/DSS model group (n=20), low-dose (14 g/kg) SBJDF group (n=10) and high-dose (42 g/kg) SBJDF group (n= 10). In the latter 3 groups, the mice were treated with azoxymethane (AOM) and dextran sodium sulphate (DSS) to induce carcinogenesis of colorectal adenoma. In the two SBJDF treatment groups, SBJDF was administered daily by gavage during the modeling. The survival rate, body weight, general condition of the mice, and intestinal adenoma formation and carcinogenesis were observed. The expressions of proteins associated with the PTEN/PI3K/AKT signaling pathway in the intestinal tissue were detected using immunohistochemistry. RESULTS: Compared with those in the model group, the mice treated with SBJDF, especially at the high dose, showed a significantly lower incidence of intestinal carcinogenesis and had fewer intestinal tumors with smaller tumor volume. Pathological examination showed the occurrence of adenocarcinoma in the model group, while only low-grade and high-grade neoplasia were found in low-dose SBJDF group; the mice treated with high-dose SBJDF showed mainly normal mucosal tissues in the intestines with only a few lesions of low-grade neoplasia of adenoma. Compared with those in the control group, the mice in the model group had significantly elevated plasma miRNA-222 level (P < 0.05), which was obviously lowered in the two SBJDF groups (P < 0.01). The results of immunohistochemistry revealed that compared with the model group, the two SBJDF groups, especially the high-dose group, had significantly up-regulated expressions of PTEN, P-PTEN and GSK-3β and down-regulated expressions of p-GSK-3 β, PI3K, AKT, P-AKT, β-catenin, c-myc, cyclinD1 and survivin in the intestinal tissues. CONCLUSION SBJDF can significantly inhibit colorectal adenoma formation and carcino-genesis in mice possibly through regulating miRNA-222 and affecting PTEN/PI3K/AKT signaling pathway.
Animals ; Male ; Mice ; Adenoma/prevention & control* ; Azoxymethane/adverse effects* ; Carcinogenesis/drug effects* ; Colorectal Neoplasms/prevention & control* ; Dextran Sulfate/adverse effects* ; Disease Models, Animal ; Glycogen Synthase Kinase 3 beta/metabolism* ; Mice, Inbred C57BL ; MicroRNAs/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Drugs, Chinese Herbal/therapeutic use*

ObjectiveTo analyze the transcriptome characteristics of Xianlian Jiedu prescription （XLJDP） in the intervention of colorectal carcinoma by high-throughput cDNA-sequencing （RNA-seq）. MethodNinety male C57BL/6 mice were randomly divided into the control group， colorectal carcinoma due to dampness， heat， stasis， and toxin model group， and XLJDP group， with 30 mice in each group. Mice in the model group and XLJDP group were fed a high-fat diet and provided with azoxymethane and dextran sodium sulfate （AOM/DSS） for inducing colorectal carcinoma. Those in the XLJDP group were further treated with intragastric administration of 12.9 g·kg^-1 XLJDP since the day of modeling for 112 days. The colorectal tissues were collected from each group 4 h after the last drug treatment and stained with hematoxylin-eosin （HE） and methylene blue for observing the pathological changes. The total RNA was extracted from colorectal tissues for RNA-Seq-based transcriptome profiling， followed by gene oncology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analysis and the screening and verification of differentially expressed genes. ResultCompared with the model group， XLJDP significantly relieved the colorectal congestion and edema and decreased tumor number and volume in mouse colorectal tissues. The methylene blue staining results indicated that XLJDP significantly suppressed the development of aberrant crypt foci （ACF，P<0.01）. As revealed by HE staining， XLJDP significantly alleviated the injury and dysplasia of colorectal tissues. Transcriptome analysis identified 615 differentially expressed genes （446 up-regulated and 169 down-regulated） between the model group and the blank group and 54 differentially expressed genes （29 up-regulated and 25 down-regulated） between the XLJDP group and model group. XLJDP mainly affected the expression of NIMA-related protein kinase 7 gene （Nek7， P<0.01）， Mucin 16 （Muc16， P<0.01）， SiahE3 ubiquitin protein ligase family member 3 （Siah3， P<0.01）， regenerating islet-derived protein 3-gamma （Reg3g， P<0.01）， RNA polymerase Ⅱ elongation factor-associated factor 2 （Eaf2， P<0.01）， transforming growth factor‐alfa gene （TGF-α， P<0.05）， secretoglobin family 1A member 1 （Scgb1a1， P<0.05）， family with sequence similarity 227 member B （Fam227B， P<0.05）， cytochrome P450 family 2 subfamily c polypeptide 40 （Cyp2c40， P<0.01）， and ankyrin repeat and EF-hand domain containing protein 1 （Ankef1， P<0.05）. Enrichment analysis showed that intestinal epithelial cell proliferation， metabolism of xenobiotics by cytochrome P450， and arachidonic acid metabolism signaling pathway were significantly enriched. ConclusionXLJDP is able to interfere with colorectal tumorigenesis and development due to dampness， heat， stasis， and toxin in mice， which has been proved by transcriptome analysis to be related to the regulation of metabolism-related pathways.

ObjectiveTo explore the effect of Xianlian Jiedu prescription （XLJDP） on the proliferation and glycolysis of human colorectal cancer HCT-116 cells and the underlying mechanism. MethodHCT-116 cells were cultured with XLJDP and then the survival rate was examined by methyl thiazolyl tetrazolium （MTT） assay. The effect on the HCT116 cell proliferation was detected by colony formation assay and 5-ethynyl-2′-deoxyuridine （EDU） incorporation assay. The amount of glucose consumed by HCT-116 cells was measured by glucose test kit， and the amount of produced lactic acid was determined by lactic acid test kit 48 h after the treatment with XLJDP. The expression of glycolysis-related proteins mammalian target of rapamycin （mTOR）， phosphorylated mTOR （p-mTOR）， glucose transporter 1 （GLUT1）， and lactate dehydrogenase （LDHA） was detected by Western blot. ResultThe half-maximal inhibitory concentration （IC₅₀） of XLJDP against HCT-116 cells was 6.82 g·L^-1. Compared with the blank group， XLJDP （1.625， 3.25， 6.50 g·L^-1） inhibited the proliferation of HCT-116 cells （P<0.05， P<0.01）. Moreover， compared with the blank group， XLJDP （1.625， 3.25， 6.50 g·L^-1） suppressed glucose uptake and lactic acid production in a dose-dependent manner （P<0.05， P<0.01）. The expression of p-mTOR/mTOR， LDHA， and GLUT1 was down-regulated by XLJDP （P<0.05， P<0.01）. ConclusionXLJDP can significantly inhibit the proliferation and the Warburg effect of glycolysis in colorectal cancer cells by regulating the mTOR signaling pathway and the down-regulating the expression of LDHA， GLUT1， and other key proteins and enzymes in glycolysis.

ObjectiveTo study the effect of Xianlian Jiedu prescription （XLJDP） on the activation of nuclear transcription factor-κB （NF-κB） signaling pathway induced by bromodomain-containing protein 4 （Brd4） in hypoxic microenvironment and to explore its mechanism in inhibiting the proliferation of colorectal cancer HT-29 cells. MethodThe human colorectal cancer HT-29 cells were cultured in a hypoxic incubator or normoxia incubator and treated with XLJDP at 0.8，1，1.2，1.6，3.2，6.4，and 12.8 g·L^-1 for 48 h， respectively. Following the detection of cell vitality using methyl thiazolyl tetrazolium （MTT） colorimetry， the effects of XLJDP （1.25，2.5，and 5 g·L^-1） on the cell mitochondrial membrane potential were determined using a fluorescent probe （JC-1）， and the apoptosis of colorectal cancer HT-29 cells was detected by flow cytometry. The cell colony formation assay and 5-ethynyl-2'-deoxyuridine （EDU） staining were conducted to test the proliferation of colorectal cancer HT-29 cells. The Western blot was carried out to measure the expression levels of Brd4 and its downstream relevant proteins such as c-Myc and hexamethylene bisacetamide-inducible protein 1 （HEXIM1）， as well as the effects of XLJDP on related proteins in the NF-κB signaling pathway. ResultCompared with the blank control group， XLJDP at 0.8，1，1.2，1.6，3.2，6.4，and 12.8 g·L^-1 inhibited the vitality of colorectal cancer HT-29 cells （P<0.05 ， P<0.01）， with the median inhibitory concentration （IC₅₀） under the hypoxic condition higher than that under the normoxia condition. Compared with the blank control group， XLJDP at 1.25，2.5，and 5 g·L^-1 significantly decreased the mitochondria membrane potential， enhanced the apoptosis （P<0.05，P<0.01）， and lowered the number of cell colonies and also the EDU-positive cells （P<0.05， P<0.01）. The results of Western blot showed that compared with the blank control group， XLJDP at 1.25，2.5，and 5 g·L^-1 down-regulated Brd4， c-Myc， p-NF-κB p65， and p-IκBα protein expression to varying degrees and up-regulated the expression of HEXIM1 （P<0.05， P<0.01）. ConclusionIn the hypoxic microenvironment， XLJDP inhibits the proliferation of colorectal cancer HT-29 cells regulated by Brd4， which may be related to its inhibition of the activation of NF-κB signaling pathway.

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines. METHODS: A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19. RESULTS: A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P < 0.001), and/or diarrhea (OR: 2.629, 95% CI: 1.109-6.231, P = 0.028) on admission had a higher risk of severe disease. Moreover, stratification analysis indicated that male patients with diabetes were more likely to have severe COVID-19 (71.4% vs. 28.6%, χ2 = 8.183, P = 0.004). CONCLUSIONS The clinical characteristics of those with severe and nonsevere COVID-19 were significantly different. The elderly, male patients with COVID-19, diabetes, and presenting with cough and/or diarrhea on admission may require close monitoring to prevent deterioration.
Adult ; COVID-19/pathology* ; China/epidemiology* ; Comorbidity ; Cough ; Cross-Sectional Studies ; Diarrhea ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors