Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis. Results After Bonferroni correction,the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population. Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

OBJECTIVE: To observe effects of restraint position on the changes of diaphragmatic mechanical characteristic in rats, and try to explore the role of nitric oxide (NO). METHODS: Rat model of restraint position was established. Rats were divided into control group, restraint position 12h and 24h groups. The markers of respiratory functions in vivo and the biomechanical markers of diaphragmatic characteristic ex vivo were evaluated. Serum NO levels were measured with spectrophotometry. The expressions of nNOS and iNOS mRNA in diaphragm were detected using RT-PCR. RESULTS: Compared with control group, respiratory rate, tidal volume and minute ventilation were significantly decreased in the restraint position 12h and 24h groups. Pt of diaphragm significantly decreased and force-generating capacity reduced at low frequency stimulation in 12h group. Force-generating capacity over the full range reduced at low and high frequency stimulation in 24h group. Pt of diaphragm in control and restraint position groups increased after L-NNA pre-incubation. Force-frequency relationship after L-NNA pre-incubation reduced in 24h group. NO level in serum increased significantly in the restraint position groups. Diaphragmatic nNOS mRNA expression was upregulated significantly in the restraint position groups. CONCLUSION Restraint position induces the decreasement of diaphragmatic contractility and the decreasement is mediated by NO from diaphragm or circulation blood.
Animals ; Biomechanical Phenomena ; Diaphragm/physiopathology* ; Male ; Muscle Contraction/physiology* ; Muscle Tonus/physiology* ; Nitric Oxide/metabolism* ; Nitric Oxide Synthase/metabolism* ; Posture ; RNA, Messenger/metabolism* ; Rats ; Rats, Sprague-Dawley ; Respiration Disorders/physiopathology* ; Restraint, Physical ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo explore the association of polymorphisms of metabolizing enzyme genes with chronic benzene poisoning (CBP) comprehensively by case-control design.

METHODS152 CBP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. 30 single nucleotide polymorphisms (SNPs) in 13 genes such as CYP2E1 were tested by PCR-RFLP, sequencing approaches. Logistic regression model was used to detect main effects and 2-order interaction effects of gene and/or environment. Multifactor dimensionality reduction (MDR) was used to detect high-order gene-gene or gene-environment interactions.

RESULTSBased on logistic regression, the main effects of GSTP1 rs947894, EPHX1 rs1051740, CYP1A1 rs4646903, CYP2D6 rs1065852 and rs1135840 were found to be significant (P < 0.05) while the confounding factors of sex, cigarette smoking, alcohol consumption and the intensity of benzene exposure were controlled. EPHX1 rs1051740 might be associated with CBP (P = 0.06). There existed 3 types of interactions were as followed: interactions of GSTP1 rs947894 with alcohol consumption, CYP2E1 rs3813867 with EPHX1 rs3738047, EPHX1 rs3738047 with alcohol consumption(P < 0.05), while the main effects of CYP2E1 rs3813867 and EPHX1 rs3738047 were not significant (P > 0.05). The other SNPs did not show any significant associations with CBP. According to MDR, a 3-order interaction with the strongest combined effect was found, i.e. the 3-factor combination of CYP1A1 rs4646903, CYP2D6 rs1065852 and CYP2D6 rs1135840.

CONCLUSIONGene-gene, gene-environment interactions are important mechanism to genetic susceptibility of CBP.

Adult ; Benzene ; poisoning ; Case-Control Studies ; Cytochrome P-450 CYP1A1 ; genetics ; Cytochrome P-450 CYP2D6 ; genetics ; Cytochrome P-450 CYP2E1 ; genetics ; Epoxide Hydrolases ; genetics ; Female ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Multifactor Dimensionality Reduction ; Occupational Exposure ; Polymorphism, Single Nucleotide ; Young Adult

OBJECTIVETo explore the association between DNA damage induced by vinyl chloride monomer (VCM) and polymorphisms of DNA repair genes and xenobiotic metabolism genes of VCM.

METHODSComet assay was employed to detect DNA damage. Based on the status of DNA damage, the VCM exposure workers were divided into two groups: DNA damage group (75) and control group (75). Case-control design was used to investigate the association between the genetic polymorphisms and DNA damage induced by VCM. Genotypes of XRCC1 (Arg194Trp, Arg280His and Arg399Gln), XPD (Ile199Met, Asp312Asn and Lys751Gln) and CYP2E1 were identified by the PCR-RFLP. PCR assay was used to detect positive and null genotype of GSTT1 and GSTM1.

RESULTSUnivariate analysis showed that the CYP2E1 c1c2/c2c2 and XPD751 Lys/Gln and Gln/Gln genotypes were significantly associated with the increased levels of DNA damage, XRCCI 339 Arg/Gln and Gln/Gln genotypes were significantly associated with the decreased levels of DNA damage (P < 0.01, P < 0.05, respectively). Logistic regression analysis showed that there was significant association between the genotypes of XRCC1 194, XRCC1 399, XPD 751, CYP2E1 and DNA damages. A prominent risk decreasing of DNA damage was observed for those individuals possessing XRCC1 399Arg/Gln + Gln/Gln genotypes (OR: 0.35, 95%CI: 0.12 approximately 1.01, respectively); The results also showed that there were significant associations between CYP2E1 c1c2/c2c2 and DNA damage both in high and low VCM-exposed groups (OR: 2.57, 95%CI: 1.01 approximately 6.59 and OR: 2.57, 95%CI: 0.99 approximately 6.87).

CONCLUSIONCumulative exposure dose and genotypes of XRCC1 194, XRCC1 399, XPD 751 and CYP2E1 may modulate the DNA damage induced by VCM exposure.

Case-Control Studies ; Comet Assay ; DNA Damage ; drug effects ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Occupational Exposure ; Polymorphism, Single Nucleotide ; Vinyl Chloride ; toxicity ; Workplace

Brain Injuries ; pathology ; surgery ; China ; Craniotomy ; Earthquakes ; Hematoma, Epidural, Cranial ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Time Factors ; Treatment Outcome

OBJECTIVETo explore the relationship between polymorphisms of natural resistance-associated macrophage protein 1 (NRAMP1) gene and genetic susceptibility of pulmonary tuberculosis (PTB) in workers exposed to silica dusts.

METHODSA 1:2 case control study of 61 male workers with PTB (50 silicosis patients and 11 unsilicosis workers) as the case group and 122 male PTB-free workers (100 silicosis patients and 22 unsilicosis workers) as the control group was conducted with the frequency matched for age of +/- 5 years, the job, the silica exposure, and the condition of cigarette smoking and alcohol drinking. The polymerase chain reaction-restrained fragment length polymorphism technique (PCR-RFLP) was used to detect the single nucleotide polymorphisms (SNPs) of NRAMP1 INT4 and D543N.

RESULTSThere was a 2.73 times (95% CI: 1.32 approximately 5.64) increased risk of silicosis for individuals with C allele of NRAMP1 INT4 compared with individuals carrying homozygote (G/G), while SNPs of NRAMP1 D543N was not associated with PTB (P > 0.05).

CONCLUSIONThe G > C mutation of intron 4 of NRAMP1 gene might be a susceptible factor of silica for the workers exposed to PTB.

Aged ; Alleles ; Case-Control Studies ; Cation Transport Proteins ; genetics ; Genetic Predisposition to Disease ; Humans ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Silicosis ; complications ; Tuberculosis, Pulmonary ; complications ; genetics

OBJECTIVETo explore the relationship between genetic polymorphisms of CYP-1A1 and CYP2D6 and risks of chronic benzene poisoning (BP).

METHODSA case control study was conducted. 152 BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were involved. Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) technology was used for detecting the single nucleotide polymorphisms (SNPs) of MspI in the non-coding region of CYP-1A1 gene and c.188, g.212 position in the first extron of CYP2D6 gene.

RESULTSThe individuals with CYP1A1 MspI T/T genotype had a 1.32 times (95% CI: 1.05 approximately 1.65, P = 0.02) increased risk of BP compared with those carrying T/C and C/C genotypes. In no-smoking population, there was a 1.56 times (95% CI: 1.15 approximately 2.12, P = 0.003) increased risk of BP for subjects carrying CYP1A1 MspIT/T genotype compared with those carrying T/C and C/C genotypes. The individuals carrying CYP2D6 c.188 C/C or C/T genotype had a 1.23 times (95% CI: 1.05 approximately 1.42, P = 0.01) increased risk compared with those carrying T/T genotypes. In no-smoking population, there was a 1.23 times (95% CI: 1.04 approximately 1.47, P = 0.01) increased risk of BP for subjects carrying CYP2D6 c.188 C/C or C/T genotypes compared with those carrying T/T genotype. The single nucleotide polymorphism of g.212 position in the first extron of CYP2D6 gene had not been validated.

CONCLUSIONThe individuals with CYP2D6 c.188 C/C, CYP2D6 c.188 C/T and CYP1A1 MspIT/T genotypes tend to be more susceptible to benzene toxicity.

Adolescent ; Adult ; Benzene ; poisoning ; Case-Control Studies ; Chronic Disease ; Cytochrome P-450 CYP1A1 ; genetics ; Cytochrome P-450 CYP2D6 ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Occupational Diseases ; genetics ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length

OBJECTIVETo explore the relationship between genetic polymorphisms in hMTH1, hOGG1 and hMYH and risks of chronic benzene poisoning (CBP).

METHODSA case control study was conducted. One hundred and fifty-two BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. The polymerase chain reaction restrained fragment length polymorphism technique (PCR-RFLP) was applied to detect the single nucleotide polymorphisms (SNPs) on c.83 of hMTH1 gene, c.326 of hOGG1 gene and c.335 of hMYH gene.

RESULTSThere were 2.51 times (OR(adj) = 2.51, 95% CI: 1.14-5.49, P = 0.02) and 2.49 times (OR(adj) = 2.49, 95% CI: 1.52-4.07, P < 0.01) risks of BP for individuals carrying genotypes of hMTH1c.83Val/Met + Met/Met or hOGG1c.326Cys/Cys compared with individuals carrying genotypes of hMTH1c.83Val/Val or hOGG1c.326Ser/Cys + Ser/Ser, respectively. Compared with individuals carrying genotypes of hOGG1c.326Cys/Cy and hMYHc.335 is/His at the same time, there was 0.33 times (OR(adj) = 0.33, 95% CI = 0.15-0.72, P = 0.01) risks of BP for these with genotypes of hOGG1c.326Ser/Cys + Ser/Ser and hMYHc.335His/Gln + Gln/Gln simultaneously. In the smoking group, there was 0.15 times (OR(adj) = 0.15, 95% CI: 0.03-0.68, P = 0.01) risks of BP for subjects carrying genotypes of hMYHc.335His/Gln + Gln/Gln compared with these carrying genotypes of hMYHc.335His/His.

CONCLUSIONPolymorphisms of hMTH1 Val83 Met and hOGG1 Ser326Cys may contribute to altered risks of CBP, and potential interaction may exist among polymorphisms of hOGG1 Ser326Cys and hMYH His335Gln.

Adult ; Benzene ; poisoning ; Case-Control Studies ; Chronic Disease ; DNA Glycosylases ; genetics ; DNA Repair Enzymes ; genetics ; Female ; Humans ; Male ; Middle Aged ; Occupational Exposure ; Phosphoric Monoester Hydrolases ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

OBJECTIVETo explore the relationship between genetic polymorphisms of microsomal epoxide hydrolase (mEH) and susceptibility of chronic benzene poisoning (BP).

METHODA case-control study was conducted. 152 BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. Polymerase chain reaction-restrained fragment length polymorphism technique (PCR-RFLP) was applied to detect the single nucleotide polymorphisms (SNPs) on c.113 and c.139 of mEH gene.

RESULTSThe risk of BP for individuals carrying mEHc.113 C/C genotype was 0.60 (OR = 0.60, 95% CI: 0.37 - 0.97, P = 0.04) of those carrying T/T and T/C genotypes. In non-smoking population, the risk of BP for subjects carrying mEHc.113 C/C genotype was 0.56 (OR = 0.56, 95% CI: 0.33 - 0.96, P = 0.03) of those carrying T/T and T/C genotypes, and in non-drinking population, the individuals carrying mEHc.113 C/C genotype was 0.51 (OR = 0.51, 95% CI: 0.30 - 0.86, P = 0.01) of those carrying T/T and T/C genotypes.

CONCLUSIONThe subjects carrying mEHc.113 C/C genotype and together with non-smoking or non-drinking habit may have lower risk of chronic benaene poisoning.

Adult ; Benzene ; metabolism ; poisoning ; Case-Control Studies ; Epoxide Hydrolases ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Life Style ; Male ; Middle Aged ; Occupational Diseases ; genetics ; Point Mutation ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length