OBJECTIVETo investigate the correlation between blood concentrations of tacrolimus (FK506) and cystatin C (Cys C) and the effect of FK506 on glycolipid metabolism in renal transplant recipients.

METHODSA total of 325 patients receiving renal transplantation between August, 2014 and September, 2015 in Nanfang Hospital were divided into 4 groups according to the postoperative time (1 month group, 1-3 months group, 4-6 months group, and 7-12 months group). FK506 blood trough concentration was measured at the time of postoperative follow-up, and creatinine (Scr) and Cys C levels were also detected. Results Plasma FK506 concentration decreased with age in the recipients and showed a positive correlation with Cys C (r=0.985, P=0.015) but no obvious correlation with Scr (r=0.259, P=0.741). FK506 had no effect on blood glucose (5.53-5.59 mmol

CONCLUSIONFK506 does not affect the level of glycolipid metabolism in patients after renal transplantation. Cys C is positively related to blood concentration of FK506 in the renal transplantation recipients. The rational use of FK506 can improve the effectiveness and safety of the treatment in the recipients.

OBJECTIVETo explore the expression and clinical significance of VEGF, IL-17, β2-MG and IL-35 in patients with multiple myeloma.

METHODSA total of 83 patients with multiple myeloma (MM) from January 2012 to December 2016 were enrolled in MM group, 36 healthy subjects were enrolled in control group. The levels of IL-17, IL-35 and VEGF in serum were detected by ELISA. The levels of β2-MG in serum were measured by radioimmunoassay. The differences of different indexes between 2 groups were compared.

RESULTSThe serum levels of IL-17, VEGF and β2-MG in serum of III stage were higher than that in II stage, which was higher than that in I stage and control group (P<0.05). The levels of IL-35 in the control group were significantly higher than those in the I,II,III stage group (P<0.05). The levels of IL-17, VEGF and β2-MG in serum of progress period were higher than those in stable phase and control group, level of IL-35 in serum of control group was significantly higher than that in the stable phase and progress period group (P<0.05). The correlation analysis showed that the level of serum IL-17 positively correlated with VEGF, β2-MG expression (r=0.65, 0.58, P<0.05); and the serum IL-17 levels were negatively correlated with IL-35 levels (r=-0.42, P<0.05).

CONCLUSIONThe anomalous levels of IL-17, IL-35, IVEGF and β2-MG expressions correlate with the progression and prognosis of patients with multiple myeloma.

Adolescent ; Child ; Child, Preschool ; Chorda Tympani Nerve ; diagnostic imaging ; surgery ; Cochlear Implantation ; methods ; Female ; Humans ; Male ; Radiography ; Young Adult

OBJECTIVETo evaluate the clinicopathologic features of gastrointestinal stromal tumor (GIST) with synchronous carcinoma and the treatment principle.

METHODSNineteen cases of GIST with synchronous carcinoma were collected from 113 cases of GIST from 2002 to 2008. The clinicopathologic features were studied and the expression of CD117, CD34, smooth muscle actin and S-100 protein were detected by immunohistochemistry using EliVision method. The expression of proliferation marker Ki-67 was also studied. GIST with synchronous carcinoma and those without carcinoma were compared.

RESULTSNineteen cases (16.8%) of GIST with synchronous carcinoma were found, including 11 males and 8 females (male to female ratio 1.38: 1.00). The age of the patients ranged from 43 to 66 years (median age 57 years). Five of 19 cases were located in the inferior segment of esophagus and 14 were in the gastric wall. The diameter ranged from 0.6 to 3.8 cm [mean (1.91 ± 0.92) cm]. Three of 19 cases showed low grade dysplasia, and there was no dysplasia in the remaining 16 cases. The number of mitosis ranged from 0 to 4/50 HPF [mean (0.74 ± 1.07)/50 HPF]. The Ki-67 proliferative index (number of Ki-67 positive cell/HPF) ranged from 0 to 7.72% [mean (2.51 ± 2.20)%]. The synchronous carcinomas included two esophageal carcinomas and 17 gastric cancers.In contrast, patients of GIST without carcinoma included 52 males and 42 females (male to female ratio 1.24: 1.00). The age of patients ranged from 43 to 71 years (median age 55 years). Seventy-nine of the 94 cases were located in the stomach, 10 were in the intestine and 5 were in the esophagus. The diameter ranged from 2.4 to 15.5 cm [mean (5.42 ± 6.17) cm].Seventy-nine of the 94 cases showed variable degrees of dysplasia, and 12 cases were of high malignant potential. The number of mitosis ranged from 0 to 53/50 HPF [average (3.78 ± 10.22)/50 HPF]. The Ki-67 proliferative index ranged from 0 to 37.54% [mean (6.78 ± 12.45)%]. Comparing these two groups, the male to female ratio of GIST with synchronous carcinoma was higher than that of GIST without carcinoma. The average diameter of GIST with synchronous carcinoma was smaller than of those without carcinoma. The number of mitosis and Ki-67 proliferative index of GIST with synchronous carcinoma were significantly lower than those without carcinoma (t' = 2.809, P < 0.05; t' = 3.095, P < 0.05, respectively).

CONCLUSIONSSixteen point eight percent of GIST may be associated with synchronous carcinoma. There are no special clinical symptoms in most of GIST with synchronous carcinoma, as these GIST are usually incidental findings. The Ki-67 proliferative index of GIST with synchronous carcinoma is significantly lower than that of GIST without synchronous carcinoma. Most GIST with synchronous carcinoma can be treated by the standard treatment for the accompanying carcinoma, and do not require specific additional treatments.

Adenocarcinoma ; metabolism ; pathology ; therapy ; Adenocarcinoma, Mucinous ; metabolism ; pathology ; therapy ; Adult ; Aged ; Antigens, CD34 ; metabolism ; Carcinoma, Signet Ring Cell ; metabolism ; pathology ; therapy ; Carcinoma, Squamous Cell ; metabolism ; pathology ; therapy ; Chemotherapy, Adjuvant ; Esophageal Neoplasms ; metabolism ; pathology ; therapy ; Esophagectomy ; Female ; Follow-Up Studies ; Gastrectomy ; Gastrointestinal Stromal Tumors ; metabolism ; pathology ; therapy ; Humans ; Ki-67 Antigen ; metabolism ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasms, Multiple Primary ; metabolism ; pathology ; therapy ; Proto-Oncogene Proteins c-kit ; metabolism ; Radiotherapy, Adjuvant ; Stomach Neoplasms ; metabolism ; pathology ; therapy

This study was aimed to investigate the relation of glutathione S-transferase pI (GSTP1) and cytochrome P450 enzyme 2E1 (CYP2E1) gene polymorphisms with the susceptibility to acute leukemia (AL) in Chinese population. The GSFP1 and CTP2E1 gene polymorphisms in 150 patients with AL and 150 patients with non-hematological diseases or non-tumor as controls were detected by means of case-control paired 1:1 method and ligase detection reaction (LDR) techniques. The results indicated that the frequently of G allele and Ile/Val + Val/Val of GSTP1 gene (26.7%and 44% respectively) in AL group were higher than those in control group (10% and 16% respectively); the AL risk for persons with Ile/Val + Val/Val was 3.260-fold (95%CI = 1.527 - 5.236) of persons with Ile/Ile. The further stratified analysis showed the frequency of Ile/Val + Val/Val in AML group was higher than that in control group (55% vs 16%, p < 0.05); the AML risk for persons with Ile/Val + Val/Val was 2.214-fold (95% CI = 1.009-3.260) as persons with Ile/Ile. The frequencies of C2 allele (16.7%) and C1C2/C2C2 of CYP2E1 gene (30%) in AL group seemed higher than those in control groups (13.9% and 26%), but the difference between them was not statistical significant (p > 0.05). The further stratified analysis showed that C1C2/C2C2 of CYP2E1 gene occurred more frequently in AML group (36%) than that in control group (32%), but there was no statistical difference between them (p > 0.05). Combined genotype analysis showed that the AML risk for persons in combination of lle/Val + Val/Val of GSTP1 gene with C1C2 + C2C2 of CYP2E1 gene increased by 3.208-fold. It is concluded that the GSTP1 gene is related with susceptibility to AML, the AL risk for persons with lle/Val + Val/Val of GSTP1 gene decreased, while CYP2E1 gene is not related with susceptibility to AL, the AML risk for persons in combination of GSTP1 wildtype with CYP2E1 hybrid and mutant genotype can be further decreased.
Acute Disease ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Child ; Child, Preschool ; Cytochrome P-450 CYP2E1 ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Glutathione S-Transferase pi ; genetics ; Humans ; Leukemia ; genetics ; Male ; Middle Aged ; Young Adult

BACKGROUND AND OBJECTIVEIn China, there has been no established national program for cervical cancer prevention, the screening methods and experiences are especially deficient in the rural areas. The aim of this paper is to evaluate the effects of acetic acid/Lugol's iodine (VIA/VILI) used for screening of cervical cancer and pre-cancerous lesions in a rural area of China by analyzing the large-scale population-based screening data from the demonstration site.

METHODSWomen aged 30-59 years from Xiangyuan County in Shanxi Province were recruited for cervical cancer screening from 2005 to 2007. VIA/VILI was the primary screening method followed by colposcopy if the VIA/VILI was positive. Cervical lesions were diagnosed by directed biopsy under the colposcopy. The VIA/VILI negative women or cervical intraepithelial neoplasia 1 (CIN1) were re-screened using the same procedure in the next year.

RESULTSIn total, 7145 women received the cervical cancer screening, with a participation rate of 74.75%. Their average age was 42.16 years. A total of 1287 women were consecutively screened for three times from 2005 to 2007. The detection rates of CIN2, CIN3 and cervical cancer were 0.70% (9/1287), 1.01% (13/1287) and 0.23% (3/1287) for the first round screening, and were 0.22% (2/976), 0.11% (1/976) and 0% (0/976) for the second round screening, respectively. Only one CIN2 was found in the third round screening. In the years of 2006-2007, 3490 women were screened consecutively twice. The detection rates of CIN2, CIN3 and cervical cancer were 0.26% (9/3490), 0.52% (18/3490) and 0.15% (5/3490) for the first round screening, and 0.40% (14/2943), 0.40% (14/2943) and 0.03% (1/2943) for the second round screening. Likewise, 2 368 women were screened consecutively twice in the years of 2007-2008. The detection rates of CIN2, CIN3 and cervical cancer were 0.55% (13/2368), 0.25% (6/2368) and 0.12% (3/2368) for the first round screening, and 0.42 (10/2040), 0.04% (1/2040) and 0% for the second round screening. The cumulative detection rates for CIN2, CIN3 and cervical cancer were 0.81% (58/7145), 0.74% (53/7145) and 0.17% (12/7145), respectively. And 53.45% (31/58) of CIN2, 68.81% (37/53) of CIN3 and almost all cervical cancers (11/12) were found during the first round screening, except for an early stage cervical cancer (Ia). Only one CIN2 was detected in the third round screening in the same population. The average age of CIN1, CIN2, CIN3 and cervical cancer were 38.65, 40.61, 44.10 and 46.73 years, respectively.

CONCLUSIONSVIA/VILI can be used as an alternative screening method for cervical cancer and high-grade pre-cancerous lesions among the women aged 30-59 years in China's rural areas because of its low cost, easy training for the local health providers, and less depending on facilities. One round screening by VIA/VILI can detect more than a half of CIN2, two-thirds of CIN3 and almost all the cervical cancer in the population, and the detection rates of CIN2/3 can be increased by two consecutive rounds of screening.

Acetic Acid ; Adult ; Carcinoma in Situ ; diagnosis ; Carcinoma, Squamous Cell ; diagnosis ; Cervical Intraepithelial Neoplasia ; diagnosis ; China ; Female ; Follow-Up Studies ; Humans ; Iodides ; Mass Screening ; methods ; Middle Aged ; Rural Population ; Uterine Cervical Neoplasms ; diagnosis

The aim of this study was to investigate the relationship of the gene polymorphisms of myeloperoxidase (MPO) and NAD (P) H: quinone oxidoreductase 1 (NQO1) with the susceptibility to acute leukemia (AL) in Chinese Gansu population. A 1:1 paired case-control study of 150 patients with acute leukemia and 150 cancer-free inpatients as a control was conducted to detect the polymorphisms of MPO and NQO1 by LDR techniques. The results showed that the MPO-463A genotype frequency in patient group was lower than that in control group, and there was significant difference of MPO (G-463A) genotype between patient group and control group (χ(2) = 11.828, P < 0.05, OR = 0.368, 95%CI = 0.205 - 0.610). The NQO1-609T genotype frequency in patient group was higher than that in control group, and there was significant difference of NQO1 (C-609T) genotype between patient group and control group (χ(2) = 17.931, P < 0.05, OR = 1.428, 95%CI = 1.237 - 3.339). The combined gene analysis showed that the AML risk in patients carrying the wild genotypes of MPO and NQO1 was dropped to 33.6%. It is concluded that the MPO and NQO1 gene polymorphisms are associated with susceptibility to AL. The AL risk may decrease in patients carrying MPO (G-463A) mutant gene (GA/AA), while the AL risk may increase in patients carrying NQO1 (C-609T) mutant gene (TC/TT). The combined effect of MPO and NQO1 wild genotypes may further decrease AL risk.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Leukemia ; genetics ; Male ; Middle Aged ; NAD(P)H Dehydrogenase (Quinone) ; genetics ; Peroxidase ; genetics ; Young Adult

OBJECTIVETo investigate if inflammatory stress enhances liver lipid accumulation via SREBPs mediated dysregulation of low density protein receptor (LDLr) expression in apolipoprotein E, scavenger receptors class A and CD36 triple knockout (ApoE/SRA/CD36 KO) mice.

METHODS16 Male ApoE/SRA/CD36 KO mice were subcutaneously injected with 0.5 ml 10% casein or PBS. The mice were fed a Western diet (Harlan, TD88137) containing 21% fat and 0.15% of cholesterol for 14 weeks. Animals were sacrificed and blood samples were collected. The serum amyloid A (SAA), IL-6, total cholesterol (TC), LDL and high density protein (HDL) were assayed. The lipid accumulation in liver was evaluated by Oil Red O staining. The mRNA and protein expression of SREBP-2, SREBPs cleavage activating protein (SCAP) and LDLr were analyzed by Real-Time Polymerase Chain Reaction (RT-PCR) and immunohistochemistry staining.

RESULTSBlood levels of SAA [(26.60+/-3.24) ng/ml vs (14.35+/-1.73) ng/ml, P < 0.01] and IL-6 [(36.37+/-2.20) pg/ml vs (18.02+/-4.87) pg/ml, P < 0.01] were higher, while TC [(7.72+/-1.70) mmol/L vs (13.23+/-3.61)mmol/L, P less than 0.01], LDL-cholesterol [(2.94+/-0.44) mmol/L vs (9.28+/-3.66) mmol/L, P less than 0.01] and HDL cholesterol [(2.24+/-0.63) mmol/L vs (4.13+/-0.42) mmol/L, P less than 0.01] were lower in inflamed mice compared to controls. ORO staining showed that lipid accumulation in the liver was more extensive in inflamed group despite lower blood lipid levels. Meanwhile, Real Time PCR data showed inflammation induced the expression of LDLr (4.56 fold), SCAP (3.14 fold) and SREBP-2 (14.72 fold) in liver. Immunohistochemical staining also indicated increased proteins expression in the liver, which was consistent with mRNA data.

CONCLUSIONSInflammation causes lipid accumulation in liver via disrupting SREBP-2 and LDLr expression.

Animals ; Apolipoproteins E ; genetics ; Cholesterol, LDL ; metabolism ; Fatty Liver ; metabolism ; Inflammation ; metabolism ; Liver ; metabolism ; Male ; Mice ; Mice, Knockout ; Receptors, LDL ; metabolism ; Sterol Regulatory Element Binding Protein 2 ; metabolism

The circadian clock has been linked to female reproductive physiology and endocrine in mammals. Epidemiological studies of female shift workers have shown increased rates of abnormal reproduction and adverse pregnancy. But little is known how the circadian rhythms affect reproduction. The aim of the present study was to investigate the influences of circadian rhythms on estrous cycle in female mice using clock gene Rev-erb-α knock out (Rev-erb-α(-/-)) mice. To test the fertility of Rev-erb-α(-/-) mice, litter sizes were counted after mating with C57BL/6J male mice. HE staining was used to observe the change of follicle development. The number of embryos of Rev-erb-α(+/+) and Rev-erb-α(-/-) female mice was compared 1.5 d after mating with C57BL/6J male mice. Then Rev-erb-α(+/+) and Rev-erb-α(-/-) female mice were housed to adult, and daily vaginal lavage with 0.9% saline was used to monitor estrous cycle for at least 30 days. Quantity of various cells was counted on specified smears views after staining. We observed estrous cycles of Rev-erb-α(+/+) and Rev-erb-α(-/-) female mice using line plots and periodic spectrograms. The results showed that the Rev-erb-α(-/-) female mice were infertility, and the number of embryos of Rev-erb-α(-/-) females was less than that of Rev-erb-α(+/+) females. However, the follicle development of Rev-erb-α(-/-) female mice was normal. The estrous cycle of Rev-erb-α(-/-) female mice was 3.22 days longer than that of Rev-erb-α(+/+) female mice. The results suggest that loss of Rev-erb-α prolongs estrous cycle, which is probably one of the reasons for female mice infertility, and circadian rhythm is important for mammalian estrous cycle.
Animals ; Circadian Rhythm ; Estrous Cycle ; Female ; Fertility ; Litter Size ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nuclear Receptor Subfamily 1, Group D, Member 1 ; genetics ; physiology ; Pregnancy

OBJECTIVE: To analyze the expression and prognostic value of metabolism-related genes in pediatric acute lymphoblastic leukemia (ALL), and explore the potential prognostic biomarkers or therapeutic targets. METHODS: Transcriptome data from 84 children with B-cell ALL at the time of diagnosis and prior to any treatment were used to analyze the differential gene expression. A prognostic scoring system based on the expression of the metabolism-related genes was constructed using Cox and Lasso regression methods. The prognostic value of the scoring system was further assessed by multivariate Cox regression analysis. Gene set enrichment analysis was carried out by using GSEA software. RESULTS: Among the 933 metabolism-related genes, 14 up-regulated genes and 17 down-regulated genes were identified as differentially expressed genes. In addition, 8 up-regulated genes (ASS1, CKM, PTGES, ADCY5, HNMT, PHGDH, CYP4F3, AADAT) and 4 down-regulated genes (GDA, DHRS9, IDO2, UGT2B4) were selected to establish a novel prognostic scoring system. Patients in the high-risk group showed poorer survival significantly than patients in the low-risk group (P<0.05). The prognostic scoring system was still shown to be an independent prognostic factor for the survival of children with ALL after the clinical characteristics, such as gender, age, white blood cell count at initial diagnosis, cytogenetics and molecular genetics were included (HR=8.906, 95%CI: 3.114-25.470). GSEA results showed that 6 metabolism-related pathways (amino sugar and nucleotide sugar metabolism, arginine and proline metabolism, fructose and mannose metabolism, glyoxylate and dicarboxylate metabolism, pyrimidine metabolism, selenoamino acid metabolism) were enriched in the high-risk group. CONCLUSION The abnormal metabolism-related gene expression is associated with the clinical outcome of children with ALL, and these results provide potential novel prognostic biomarkers and treatment targets for pediatric ALL.
Gene Expression Profiling ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prognosis ; Transcriptome